A STUDY OF TOOTH WHITENING: SAFETY, EFFICACY AND
MECHANISM OF ACTION
Gerard Kugel
A STUDY OF TOOTH WHITENING: SAFETY, EFFICACY AND
MECHANISM OF ACTION
1
A STUDY OF TOOTH WHITENING: SAFETY, EFFICACY AND
MECHANISM OF ACTION
Dipartimento di Scienze Odontostomatologiche
Università di Siena
Viale Bracci
53100 Siena
Prepared for the graduate committee on June 13, 2004
Gerard Kugel
Boston, MA, USA
2
The present thesis is respectfully submitted to Prof Piero Tosi, Rector of the University
of Siena, to Prof Alberto Auteri, Dean of the Faculty of Medicine, University
of Siena, to Prof Egidio Bertelli, vice-Dean of the Faculty of Medicine and Director of the
Department of Dental Science, and to Prof Marco Ferrari, Pro-Rector for
international affairs and President of Dental School, University of Siena.
Graduate Committee:
Promotor
Committee
Prof. Dr Marco Ferrari
Prof. Dr C.L. Davidson
Prof. Dr F. Tay
Prof. Dr Toledano
Prof. Dr Balleri
This thesis was prepared at Tufts University School of Dental Medicine, Boston MA,
USA and at the School of Dentistry University of Siena, Italy.
3
Contents
Chapters
1
Introduction
2
A Novel Low Dose Tooth-Whitening Delivery System
Efficacy and Safety: A Randomized and Controlled Clinical Trial
3
Concentration and Dose Response
Clinical Trial Evaluating the Peroxide Concentration Response of a Polyethylene
strip Delivery System over 28 Day
4
Light activated Tooth Whitening
Clinical Evaluation of a 35% Hydrogen Peroxide In-Office Whitening System
5
Chemical Vs Light activated Tooth Whitening
Clinical Evaluation of Chemical And Light-Activated Tooth Whitening Systems
6
Tooth whitening and its Effect on Enamel and Dentin
Daily Use of Whitening Strips on Tetracycline Stained Teeth: Comparative Results
after Two Months
7
Long Term Hydrogen Peroxide Exposure and its Effect on Dentin
Comparative Study of 6.5% Hydrogen Peroxide Bleaching Strips on Tetracycline
Stain: Clinical Response after Six Months Daily Use
8
Paint on delivery systems
A clinical Comparison of two Paint on Whitening Systems
9
Maintenance of Whitening
Clinical Study to Evaluate the Maintenance of Whitening after Bleaching Treatment
4
10
Intrapulpal Temperatures with Light Activated Whitening
Effects of a Light Activated Bleaching System on Pulp Chamber Temperature in
Vitro
11
Effect of Tooth Whitening on Enamel
An exploratory study using SEM to evaluate the enamel surface effects in vivo of a
6% hydrogen peroxide strip bleaching system with that of a 2.5% chlorite tray
bleaching system
12
Summary and Conclusions
5
Chapter 1
INTRODUCTION
The dental profession has succeeded in reducing caries and periodontal diseases and as a
result dental problems have decrease to the point where esthetic improvements are now more
attainable 1. One of the fastest growing areas of esthetic dentistry today is the management of
the discolored and hypoplastic dentition. The demand for an improved appearance and a whiter
smile has made tooth whitening a very popular dental procedure. Tooth whitening, sometimes
referred to as “bleaching”, offers a conservative treatment option for discolored teeth in
comparison to resin bonded composites, porcelain veneers or crowns
2,3
. Candidates for
whitening procedures include patients whose teeth are stained by aging, chromogenic foods,
endodontic treatment, tetracycline use and smoking or use of other tobacco products. Success
of the treatment depends on type, intensity and location of the discoloration and a careful
diagnosis by the practitioner.
History of Tooth Whitening
Many attempts to find an effective bleaching method have been made through out the history of
dentistry. The desire to have whiter teeth dates back at least 2000 years ago. During the first
century the Romans physicians claimed the use of urine, especially Portuguese, to brush the
teeth would whiten the teeth 4. Barber-surgeons used a solution of nitric acid to lighten the teeth
after using a course metal file to abrade the enamel 4, practice until late eighteenth century.
In 1895 it was reported the combination use of pyrozone 25% and electricity to bleach the
endodontically treated teeth 5. Later on, in 1916, it was stated the use of hypochloric acid to
treat endemic fluorosis 6. In 1939 it was advocated the use of 30% hydrogen peroxide, ether
6
and heat to treat fluorosis staining 7. In 1966, it was promoted the combination use of
hydrochloric acid and hydrogen peroxide to remove “brown stain from mottled teeth” due to a
chronic endemic dental fluorosis 8. The early efforts to whiten teeth relied on the assumption
that the process involved the removal of extrinsic enamel stain. The mechanism of action was
poorly understood.
It was only on 1970 that Cohen and Parkins first published a method for bleaching the
discolored dentin of young adults with cystic fibrosis who has undergone tetracycline treatment
9
. This publication indicated that the mechanism of tooth whitening using hydrogen peroxide
involves penetration to the dentin. In 1976, Nutting and Poe introduced the walking bleach
technique, which uses 35% hydrogen peroxide and sodium perborate for nonvital teeth
bleaching10. The breakthrough in tooth whitening was in 1989 when Haywood and Heymann
published the nightguard vital bleaching technique
11
. This is procedure is still widely used
among the dental community as the take-home bleaching system.
Tooth Whitening Systems
Tooth whitening with various concentrations of peroxide has been demonstrated to be safe and
effective in a variety of regimens, including in-office procedures, dentist-prescribed and
supervised home treatments and over the counter system approaches
12
. Most dental practices
in the United States offer some form of tooth whitening system.
A) Take- home System
The most common regimen is the at-home use for 2 to 4 weeks, based on the color of the teeth
at the start of whitening
13,11
.The use of hydrogen peroxide for removing intrinsic stains from
vital teeth has been used for many years. Haywood and Heymann published the first article
describing night guard vital bleaching in 1989
11
. A tray is fabricated from a model of the
patient’s teeth using a soft plastic nightguard. This tray is the loaded with carbamide peroxide
7
gel and seated over the teeth for approximately 2 hours.
The most commonly prescribed
concentrations are 10% to 22% carbamide peroxide.
The advantage of the take-home systems is the decreased cost when compared to the in office
bleaching options. The major disadvantages associated with take-home systems are: (a) they
require significant patient compliance with the number of applications usually involving 1-2
hours twice a day or overnight wear, and (b) the entire treatment usually takes at least four
weeks.
B) In-Office System
The most acceptable applications involve are in-office techniques, dentist prescribed take-home
systems or a combination of both. The in-office bleaching technique generally employs a 15%,
30% or 35% hydrogen peroxide bleaching agent (heated or non-heated).
The advantages of the in-office procedure are: (a) it requires minimal patient compliance, and
(b) immediate results are attainable. The disadvantages to this treatment are: (a) chair-time
requirement, and (b) cost to the patient. It is important to note that this procedure usually
requires multiple office visits.
C) Combination Technique
By combining the two techniques (in-office and take-home), there is a reduction in the amount of
time and the need for repeated office visits as well as the expense associated with in-office
bleaching as a stand-alone technique
14
. The combined technique increases overall success
and patient satisfaction. This procedure involves the use of a high concentration of hydrogen
peroxide (35%) delivered chair side for one hour followed by a take home regimen of 5days.
This is often followed by an additional chair side application. 15
8
D) Whitening Strips
A new method involves using a 5.3% hydrogen peroxide-impregnated polyethylene strip
(CrestWhitestrips) for 30 minutes twice daily. This method is recommended for maintaining
already whitened teeth. It can also be a good option to patients who cannot afford the cost of
other whitening treatment or who do not have the time for multiple dental visits for tray
fabrication
13
. It was published in 2002 the use of the whitening strips for tetracycline stained
teeth 13.
Development of this flexible, polyethylene whitening strips allows for consistent bleaching using
shorter contact times. Fixing the daily strip regimen at 30 minutes per day, a randomized,
double blind, a double placebo-controlled clinical study was conducted to evaluate the effects of
increasing the dosing regimen on tooth shade
17
. Also, an in vitro study explored the impact of
varying concentration of carbamide peroxide ranging from 0.4% to 10% on bleaching efficacy
and the impact of increasing hydrogen peroxide concentration on bleaching strip efficacy and
tolerability under clinical conditions
18
. These studies demonstrated that a modest increase in
peroxide concentration on a flexible bleaching strip results in increased whitening effectiveness,
without adversely impacting on overall tolerability.
E) Light Activated Whitening Systems
The introduction of light activated devices such as Plasma arc, Light Emitting Diodes (LED),
Argon lasers, metal halide and xenon-halogen lights by dental manufacturers have helped
create a public demand for the light enhanced tooth whitening systems.
Controversial papers were published evaluating the efficacy of light activated bleaching agents
in 2002. The first article reported positive results19. The other articles concluded the opposite
findings
20, 21
. These articles either maintained
22
or questioned the results
23
.
The dental
profession still needs more evidence of its effectiveness in order to provide better and more
9
efficient treatment. The high demand for “up to date” dental office by patients and clinicians
stimulates manufacturers to inundate the dental profession with advertisements emphasizing
that light activated tooth whitening is “the state of the art” and should be part of the
armamentarium of the office, with not clear evidence of its usefulness.
The use of hydrogen peroxide (H202) for bleaching teeth has been evident with use of heat or
not 24. In order to gain treatment time, clinicians have attempted to accelerate the degradation of
H202 by using heat or light. Cohen and Parkins introduced a technique for bleaching discolored
teeth using hydrogen peroxide and a hand-held heating source 9.
Recent in vitro study has shown that the use of intense lights does elevate temperature of the
bleaching material and as a result caused an increase in intrapulpal temperature. This may
have an impact on post bleaching tooth sensitivity and pulpal health 25 . Another research in vitro
has verified that the use of laser-activated hydrogen peroxide did not produce any perceivable
colour change 26. Light-activated chair side bleaching systems probably offer the benefit of
being less time-consuming while producing faster results.
The assumption is that clinically tolerable levels of heat will speed the breakdown of H2O2 tooth
bleaching chemicals and this accelerated H2O2 breakdown will cause teeth to lighten more
rapidly per unit time. In a recent study the decomposition of hydrogen peroxide was measured
by the amount of oxygen released. The data from this study indicated that at temperatures of up
to 85º C accelerated decomposition of the 35% H2O2 was minimal when compared to the control
gel 20.
The use of light activated bleaching system to accelerate the bleaching process is still on
question and more evidence needs to be gathered in order to make a more precise assertion of
its effectiveness.
10
F) Toothpaste
Many types of toothpaste are available in the market as tooth whitening products, but only a
small number of them show stain removal ability and effectiveness. Most of these toothpastes
do not contain bleaching agents in their formulation. The ones that do have very low bleach
concentration and contact times relatively too short to be effective
27
. Whitening toothpastes
contain mild abrasives to remove surface stains. The peroxide content in the toothpastes are
very low (1% or less), also the exposures of the toothpastes on the tooth is minimal hence any
whitening minimal 28.
G) Over the Counter Products
Easy availability of over the counter whitening products has made whitening of teeth more
popular amongst people of all ages. There are different types of over the counter products like
whitening dentifrices, tray based, whitening strips and the recently introduced brush
applications. The latest inclusion to OTC products is a Brush technique. This technique is nontray based paint on application. Gingival irritation can be prevented due to the ease in
application.
Over the counter bleaching kit requires the consumer to use either a
prefabricated tray or fabricate their own semi-molded tray then fill it with supplied bleaching
agents. These types are less than ideal because the trays are not custom fitted and the
formulation is not sophisticated as those dispensed by the dentist 29.
Mechanism of Action
Many studies have been conducted to evaluate the effectiveness of various bleaching materials
and techniques
27, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 15, 41, 42
. The brightening effect of the carbamide
peroxide and hydrogen peroxide or of both in a combined technique was reported during the
above investigations.
11
The exact mechanism of action is not completely understood. Hydrogen peroxide diffuses
through the organic matrix of the enamel and dentin 43, 44, 45. Because the radicals have unpaired
electrons, they are extremely electrophylic and unstable and will attack most other organic
molecules to achieve stability, generating other radicals. These radicals can react with most
unsaturated bonds, resulting in disruption of electron conjugation and a change in the
absorption energy of the organic molecules in tooth enamel. Simpler molecules that reflect less
light are formed, creating a successful whitening action. This process occurs when the oxidizing
agent (hydrogen peroxide) reacts with organic material in the spaces between the inorganic
salts in tooth enamel 46.
Bleaching Penetration
Enamel is the most dense tissue of the body a study conducted by Bartelstone in 1951 showed
the penetration of I-131 through enamel to dentin which diffused to pulp
47
. Carbamide peroxide
breaks down into hydrogen peroxide, carbon dioxide urea and ammonia. Some of the by
products penetrate the dentinal tubules reaching the pulp causing reversible pulpitis
43, 48
. Some
of the pulpal enzymes are sensitive to hydrogen peroxide along with heat. However, in vital
bleaching the amount peroxide reaching pulp compared to amount of H2O2 required to cause
this damage is very low
44
. Gokay et al a higher peroxide diffusion was seen in teeth with
restorations using a high concentration of carbamide peroxide compared to using a lower
concentration 48.
In vitro data using extracted human teeth have demonstrated that a 10% carbamide peroxide
gel can change the color of dentin over time 49. In this study teeth were sectioned and placed on
glass slides. The teeth were sealed at the cut surfaces and bleached for 10 days. Digital photos
were taken from marked areas and lightness values determined.
12
Sensitivity is generally mild and transient. Sensitivity occurs earlier in treatment and decreases
as treatment continues. This might occurs due to the close contact of gel to the tooth and
disappearance may be due to sensory accommodation 50.
Tooth Discoloration: External – Internal Staining
Tooth discolorations can be superficial changes that affect the enamel surface, or can be
deeper staining which affects the entire tooth structure. It is essential for the dentist to identify
the type of discoloration in the patient’s tooth, diagnose the cause and define the appropriate
treatment plan.
Tooth discoloration in vital teeth can result from aging, tobacco use,
chromogenic foods, medications and pulpal pathology 51.
Superficial discolorations are usually caused by the staining effects of certain foods, beverages,
or tobacco products. Tea, coffee, red wine, cola and smoking or chewing tobacco usually result
in yellow, brown or black staining with pits, fissures, grooves and enamel defects retaining even
more of the pigmenting effects. Yellow-brown stains are usually external and from accumulation
of environmental colorants to an irregularly formed enamel matrix. Conversely, internal staining
results from improper calcification and/or hypoplasia.
More severe discolorations result from systematically prescribed medication during tooth
formation, intake of excessive amount of fluoride during enamel formation and calcification,
different systemic conditions, dental conditions and/or treatment and aging.
In 1956,
Schwachman and Schuster first reported tooth discoloration caused by incorporation of
systemic tetracycline into tooth structure
52
. Tetracycline discoloration occurs with the systemic
intake of tetracycline during tooth formation (second trimester in uterus to 8 years of age). The
discoloration of the permanent dentition depends on the amount and duration of tetracycline use
53
. The portion of the tooth, color and severity of the stains can be determined by the stage of
the tooth development at the time of the drug administration. Tetracycline is incorporated into
13
dentin during tooth calcification intra and post partum, probably through chelation with calcium
54
forming tetracycline orthophosphate
. It can be deposited in fetal tooth buds when
administered in the third trimester of pregnancy or by a child during the development of the
tooth (between ages 3 to 4 months and 7 to 8 years)
55, 56
. Colors may vary intensity of gray,
blue, brown and yellow. The different banding can also be attributed to the variations of the
tetracycline derivates
Tetracycline staining is complex, and may necessitate extensive esthetic intervention. Vital
bleaching with professional tray or strip systems can yield an evident improvement in
appearance within a few weeks. While non-invasive, treatment may need to continue over an
extended period. Some individuals will show favorable response after 3-4 months, after which
treatment may be discontinued. Duration may be difficult to predict, given the variable clinical
manifestations of tetracycline staining. Practitioners and patients should be advised that optimal
bleaching of tetracycline staining may necessitate extended daily at-home treatment over a
period of 3-6 months. The costs, risks, and benefits of the various treatment options must be
considered as part of overall patient management
57, 58
. Excessive systemic fluoride during
enamel matrix formation and calcification can result in a defective matrix and improper
calcification known as endemic enamel fluorosis or mottled enamel
59,60
.
Fluorosis usually
presents bilaterally with white chalky spots, yellow or brown staining
Systemic conditions can also cause tooth discolorations. Amelogenesis imperfecta may result
in hypoplasia or hypocalcification with yellow or brown stains and dentinogenesis imperfecta
with brownish violet, yellowish or gray discolorations
61
. Hypoplasia or hypocalcification can
occur with clefting of the lip and palate or with acquired illnesses such as cerebral palsy, serious
renal damage and severe allergies
46
. Blue, brownish or green tooth discolorations may be
caused by destruction of an excessive number of blood-cell erythrocytes in erythroblastosis
fetalis a result of Rh-factor incompatibility between mother and fetus 46, 61.
14
Patients with porphyria, a rare condition that causes an excess production of pigment, may
result in a red, purplish-brown or brownish tooth discoloration
46, 62, 63
. Dental caries, discolored
acrylic or restorations (made of composite, amalgam and/or metal), pins, posts and other
materials employed in the dental environment can have an adverse effect on tooth coloration
resulting in a darkened shade of the patient’s dentition.
Aging usually brings thinning of the
enamel, loss of the translucent enamel layer, and formation of secondary dentin. The
combination of less enamel and more darkened, opaque dentin creates an older-looking darker
tooth 46.
Tooth Whitening Protocol
Tooth whitening, when used with professional supervision, can be safe and effective. A
complete oral examination (with a review of the patient’s medical and dental history) and an
updated set of periapical radiographs are necessary before planning any bleaching procedure.
It is very important to determine the severity and cause of the tooth’s discoloration because it
will allow the dental clinician to specify which treatment plan options are to be used.
Discolorations due to medications will need longer and more persistent treatment than stains
that occurred from aging, smoking or eating habits. Existence of carious lesions, restorations,
endodontic treatment, pulpal anatomy and any periapical pathology must be determined during
the clinical and radiographic examination before the onset of the bleaching procedure
Different pulp size teeth may have different rates of response to bleaching
39
.
64
.
Existence of
caries, microcracks in enamel, exposed dentin and open margins in existing restorations must
also be taken into consideration before treatment. Restorations that are not properly sealed and
untreated carious lesions can lead to extensive sensitivity and should be treated before
beginning any bleaching treatment 46.
15
Tooth sensitivity and gingival irritation have always been a concern when tooth whitening is
used. Both in-office and take-home bleaching procedures have been reported to induce
sensitivity to a significant number of patients
65
. Tooth whitening is generally well tolerated.
Some patients may experience tooth sensitivity and mild oral mucosa irritation; however, these
symptoms are generally mild and are alleviated at the end of treatment. Tolerability may be
impacted by tray design, poor compliance or product ingestion. Tray thickness may contribute
to poor compliance by causing occlusal interferences or jaw pain 13.
Detailed clinical and radiographic examination, fabrication of a custom-fitted, well- adapted
mouth guard, careful selection of the tooth whitening material and proper patient instruction can
significantly decrease the possibility of tooth sensitivity or gingival irritation during the take-home
treatment. The tray fabrication technique should include “scalloping” of the tray material to the
gingival line to reduce the exposure of excess bleaching agent onto the soft tissues.
The thickness of the tray material (0.040” is recommended) is also important to prevent patient
discomfort and other problems associated with the temporo mandibular joint (TMJ). The design
of the tray (with reservoirs or without reservoirs) will be a determinant of the type of tooth
whitening material to be used. Selection of the product to be used should be based on the
concentration of active ingredient, viscosity and other salient features.
Teeth that have composite or amalgam restorations and are being treated with 10% carbamide
peroxide demonstrated increased microleakage in the restorations, according to a study which
evaluated the microleakage of previously restored Class II restoratives after exposure to 10%
carbamide peroxide. Microleakage of previously restored Class II restoratives after exposure to
10% carbamide peroxide 66.
16
The immediate placement of composite resin on bleached teeth has been controversial.
According to a study evaluating the shear bond strength of composite restorations placed on
bleached and non bleached teeth, there was no statistically significant difference when the
composites were placed at 24 hours, 48 hours, 4 or 6 days
67
. A different study, evaluating the
effects of take home bleaching systems on enamel surfaces, suggests that a period of 4 days
must elapse before bonding to a tooth bleached with a peroxide material, while no delay is
necessary for a non-peroxide based bleaching system 68.
Most authors and tooth whitener manufacturers recommend the use of reservoirs during
bleaching tray fabrication, in order to increase the effectiveness of the tooth whitening material
11
. Clinical studies examined the role of reservoirs reveal that the presence or absence
bleaching solution reservoirs in the bleaching tray did not increase the success of take-home
bleaching with 10% carbamide peroxide gel
69
. Tooth whitening products pH differs in a range
of 4.0 to 7.5, with more acidic pH in materials with higher peroxide concentration. It is important
that these materials have a relatively neutral pH, because root resorption, enamel
demineralization and erosion may occur with pH less than 5.2
70
. Dental lasers have been used
for tooth whitening. Currently the argon laser is the most commonly used laser for power
bleaching 71. There is not enough evidence to support safety and efficacy of laser bleaching 72.
Bleaching Side Effects
Toxicology
FDA has approved hydrogen peroxide and carbamide peroxide to be used for debriding oral
wounds. Even though bleaching is a longer process than debridment, in vitro toxicological
evaluation of bleaching agents like 10% carbamide peroxide or 4% hydrogen peroxide was
lower or comparable to commonly used dental materials like eugenol, dentifrices ,mouth rinses
and composites 12.
17
Studies have shown that daily exposure of carbamide peroxide should not exceed 10mg/kg
73
.
Li and Matis found that the average amount of bleaching agent used is 502mg per application.
Even if the patient swallows all the gel, it would not exceed more than 8.37mg /kg 12 . Therefore
the safety factor of the bleaching agent is high.
Oral Side Effects
The mucosal irritation mostly occurs due to ill fitting trays, improper application of bleaching gel
or using it for longer time than prescribed. Schulte J and others showed that the group with the
overnight exposure to the bleaching gel subjects had mucosal irritation
74
. The soft tissue
irritation generally is minimal and is resolved either by adjustment of the bleaching tray, or
shortly after cessation of the treatment 75.
Tooth Sensitivity
Studies have shown that sensitivity occurs in 55 to 75% of the treatment groups. The placebo
groups also experienced 20-30% sensitivity. One study reported tooth sensitivity of about 15 %
wearing only the bleaching tray 76,77.
The development of tooth sensitivity can be a multifactorial phenomenon. If the whitening tray is
fabricated from a thick material, it can result in an appliance producing minor orthodontic
movements
78
. Allergies and chemical sensitivity to the composition of the tray or the bleaching
gel. And the free radical formation of the whitening gel
tooth brushing during participation in a clinical trial
79
.It can also result from overzealous
77
. Glycerine which is used to carry the active
ingredient can absorb water therefore can have a dehydration effect, hence resulting in
sensitivity. 78,79.
Summary
In summary, although tooth whitening is one of the most popular dental procedures it is also one
of the least understood. We are still unclear as to its mechanism of action. There is little data of
18
the effects of both concentration and dose on outcome. The techniques for measuring color
change have been brought into question. The cause(s) of sensitivity are not clear nor are the
issues of long tern exposure to hydrogen peroxide. The issue of rebound in color has not been
well examined and issues related to maintenance of the whitening effect are also poorly
understood
Most recently there has been a push to find ways to accelerate as well as improve the delivery
of the whitening process. These include the application of a number of different light sources
believed to accelerate the breakdown of peroxide and thus speed up the whitening process.
The research in this area has been controversial with publications having quite different
conclusions as to the efficacy of light activated bleaching. In an effort to improve the delivery
systems both polyethylene strips and paint-on whitening products have been introduced. The
efficacy of the paint-on products has been questioned and little research on these products can
be found
19
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20
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131(9): 1269-77, Sept 2000.
31) Christensen GJ: Tooth bleaching, home-use products. Clinical Research Associates
Newsletter 13(7):1, 1989.
32) Cibirka RM, Myers M, Downey MC, Nelson SK, Browning WD, Hawkins IK, Dickinson
GL: Clinical study of tooth shade lightening from dentist-supervised, patient-applied treatment
with two 10% carbamide peroxide gels. J Esth Den 11(6):325-31, 1999.
21
33) Jones AH, Diaz-Arnold AM, Vargas MA, Cobb DS: Colorimetric assessment of laser and
home bleaching techniques. J Esth Den 11(2):87-94, 1999.
34) Haywood VB: Nightguard vital bleaching: a history and product update. 1. Esthet Dent
Update 2(4):63-66, 1991.
35) Haywood VB: Nightguard vital bleaching: a history and product update. II. Esthet Dent
Update 2(5):82-85, 1991.
36) Haywood VB, Heymann HO: Nightguard vital bleaching: how safe is it? Quintessence
Int 22:515-523, 1991.
37) Haywood VB: Bleaching of vital and nonvital teeth. Current Opin Dent 142-149, March
1992.
38) Haywood VB: The Food and Drug Administration and its influence on home bleaching.
Curr Opin Cosm Dent 12-8, 1993.
39) Haywood VB. Considerations and variations of dentist-prescribed, home-applied vital
tooth-bleaching techniques. [Review] [27 refs] Compendium. Suppl 17:S616-21, 1994.
40) Nathanson D, Parra C: Bleaching vital teeth: a review and clinical study. Compend
Contin Educ Dent 8(7):490-497, 1987.
41) Kugel G, Perry R, Papathanasiou, Kastali S: Combined in-office and at-home bleaching
system: An evaluation1. JDR 77:957, abstract #2604, 1998.
42) Deliperi S., Bardwell D.N., Papathanasiou A. Clinical Evaluation of a Combined InOffice and Take-Home Bleaching System. JADA The Journal of the American Dental
Association, May 2004, vol. 135, no. 5,pp. 628-634
43) Bowles WH, Ugwuneri Z: Pulp chamber penetration by hydrogen peroxide following vital
bleaching procedures. J Endod 13:375-377, 1987.
44) Bowles WH, Thompson LR: Vital bleaching: the effect of heat and hydrogen peroxide on
pulpal enzymes. J End 12:108-112, 1986.
45) Fuss A, Szajkis S, Tagger M: Tublar permeability to calcium hydroxide and the bleaching
agents. J Endod 15:362-364, 1989.
46) Goldstein RE, Garber DA: Complete dental bleaching. Quintessence books 1995.
47) Bartelstone HJ. Radioiodine Penetration through Intact Enamel with Uptake by
Bloodstream and Thyroid Gland. Journal of Dental Research October 1951; 728-733
48) Gokay O, Tuncbilek M,Ertan R. Penetration of the pulp chamber by carbamide peroxide
bleaching agents on teeth restored with composite resin. J of Endodontics 2000; 27; 92-94
49) McCaslin A.J., Haywood V.B., Potter B.J., Dickinson G.L., Russell C.M. Assessing
Dentin Color Changes From Nightguard Vital Bleaching .JADA. The Journal of the American
Dental Association, October 1999, vol. 130, no. 10,pp. 1485-1490
22
50) Michael G Jorgensen, William B. Carroll. Incidence of tooth sensitivity after home
whitening treatment. JADA vol.133 August 2002 ;1076-1082
51) Blankenau R. Goldstein RE. Haywood VB. The current status of vital tooth whitening
techniques. Compendium of Continuing Education in Dentistry. 20(8):781-4, 786, 788
passim; quiz 796, 1999 Aug.
52) Schwachman H, Schuster A: The tetracyclines applied pharmacology. Pediat Clin North
Am 3:295, 1956.
53) Christensen GJ: Bleaching vital tetracycline stained teeth. Quintessence Int.1978 Jun:
9(6): 13-9
54) Mello HS. The mechanism of tetracycline staining in primary and permanent teeth. J
Dent Child 1967; 34(6): 478
55) Moffitt JM, Cooley RO, Olsen NH, et al. Prediction of tetracycline-induced tooth
discoloration. J Am Dent Assoc 1974; 88:547-552
56) Mull MM. The tetracycline and the teeth. Dent Abstr 1967; 12:346-350
57) Haywood VB, Leonard RH, Dickinson GL. Efficacy of six months of nightguard vital
bleaching of tetracycline-stained teeth. J Esthet Dent. 9: 13-9, 1997
58) Kugel G, Aboushala A, Zhou X, Gerlach RW. Daily use of strips on tetracycline-stained
teeth: comparative results after 2 months. Comp of Cont Edu in Dent. Jan 2002; 23 (1A): 2934
59) Stewart RE et al: Pediatric Dentistry. St Louis, CV Mosby Co., p.87, 1982.
60) Swift EJ: A method for bleaching discolored vital teeth. Quint Int 19:607, 1988.
61) Shafer WG, Hine MK, Levy BL: A textbook of Oral Pathology, 3rd Ed. Philadelphia,
Saunders, 1974.
62) Jordan RE, Boksman L: Conservative vital bleaching treatment of discolored dentition.
Comp Cont Ed Dent 5(10):803-808, 1984.
63) Faunce F. Management of discolored teeth. [Review] [30 refs] Dental Clinics of North
America.27(4):657-70, Oct. 1983 .
64) Nathanson D, Parra C. Bleaching vital teeth: a review and a clinical study. Compendium
1987; 8:490-8
65) Nathanson D: Vital tooth bleaching: sensitivity and pulpal considerations. J Am Dent
Assoc., 128(Suppl): 41S-44S, 1997.
66) Bardwell D, Habib C, Kugel G, Mehta N, Leone L: Microleakage of previously restored
Class II restoratives after exposure to 10% carbamide peroxide. JDR 2000 Special Issue
Vol.79, abstract 306.
23
67) P. Yu, A. Aboushala, D. Bardwell. Effect of bleaching on Composite Resin Shear Bond
Strength In Vitro. JDR 1999 Vol.78 special issue, abstract #1445
68) MacKay M., Perry R., Swift E., Varga M. S. Effects of the two home bleaching systems
on Enamel surfaces. JDR 1997 special issue abstract #1405.
69) Javaheri DS, Janis JN: The efficacy of reservoirs in bleaching trays. Operative Dentistry,
2000, 25, 149-151.
70) Price RBT, Sedarous M, Hiltz G: The pH of tooth-whitening products. J Can Den Ass,
Sept. 2000, Vol. 66, No. 8, 421-426.
71) Sun G: The role of lasers in Cosmetic Dentistry Dental Clinics of North America, Vol. 44,
No 4, Oct. 2000, 831-849.
72) Blankenau R, Goldstein R, Haywood V: The current status of vital tooth whitening
techniques. Compendium of Continuing Education in Dentistry, Aug 1999, Vol. 20, No 8, 781794.
73) DahlJE, Becher R. Acute Toxicity of carbamide peroxide and commercially available
tooth bleaching agent in rats; Journal of dental Research 1995; 74: 710-714
74) Schulte J,Morrissette D,Gasior E,Czajewski,M. Clinical Changes on the Gingiva as a
result of at-home bleaching. Compendium 1993, VolXIV, no.11; 1362-1371
75) Haywood VB, Leonard RH, Chauncy NF, Brunson WD. Effectiveness, Side Effects and
Long Term Status of Nightguard Vital Bleaching. JADA, September 1994 ,vol.125pg 12191226
76) Haywood VB, Caughman FW,Frazier KB,Myers ML. Tray delivery of potassium nitratefluoride to reduce bleaching sensitivity. Quintessence International ,vol32,no.2,2001;105-108
77) Michael G Jorgensen, William B. Carroll. Incidence of tooth sensitivity after home
whitening treatment. JADA vol.133 August 2002 ;1076-1082
78) Pohjola R,Browning WD, Hackman ST, Michael ML, Downey MC. Sensitivity and Tooth
Whitening Agents. Journal of esthetic and Restorative dentistry 2002; vol2, no.2; 85-91, 2002
79) Leonard RH, Haywood VB, Phillips C. Risk factors for developing tooth sensitivity and
gingival irritation associated with nightguard vital bleaching. Quintessence International; 1997
vol. 28 no. 8; 527-534
24
Chapter 2
A Novel Low Dose Tooth-Whitening Delivery System
Efficacy and Safety:
A Randomized and Controlled Clinical Trial
Abstract
A randomized, single-center, double-blind, parallel-group, placebo controlled trial evaluated the
whitening efficacy and safety of 2-week, twice daily use of a 5.3% hydrogen peroxide toothbleaching gel delivered on polyethylene film. Efficacy was based on change in Vita® shade
scores from baseline to the end of treatment. Thirty-three patients in each group completed
treatment. Use of the peroxide-containing gel led to a mean change in baseline Vita® shade
score of –3.70 ± 0.35, compared with a change of –0.87± 0.24 after use of a placebo gel. After
adjustment for baseline scores, the mean difference in shade change between the peroxide
gel–treated group and placebo-treated group was –2.85 ± 0.41 (P < 0.0001). Both treatments
were generally well tolerated. The strips offer ease of use, comfort, and shorter duration of wear
compared with other at-home bleaching systems.
Introduction
Tooth whitening is one of the most widely accepted esthetic procedures today, with treatment
options that include in-office procedures, dentist prescribed home-applied systems, over-thecounter (OTC) bleaching kits, and a host of whitening dentifrices. Peroxides have been used for
tooth bleaching for more than 100 years, and at-home nightguard vital bleaching, which involves
use of a 10% carbamide peroxide gel in a custom-fitted tray, has met with much success since
its introduction in 1989.1 The safety and efficacy of carbamide peroxide bleaching agents is well
documented, and currently six products have been approved by the American Dental
Association for home whitening.2
25
Tooth discoloration in vital teeth can result from chromogenic foods, tobacco products,
medications such as tetracycline and fluoride, pulp pathology, and aging.2 Concentrations of up
to 35% peroxide have been used to resolve discoloration. The most research has been
conducted on 10% carbamide peroxide, which produces substantial lightening of treated teeth
after 2 to 6 weeks of treatment,
3, 4
although a period as long as 6 months may be required for
stubborn stains, such as those caused by tetracycline or nicotine.5 After treatment, the whitening
effect may persist for 3 or more years.
Tooth-whitening agents are remarkably well tolerated; the main adverse events are generally
mild and transient tooth sensitivity and gingival irritation.6 Nevertheless, poor compliance and
product ingestion are problems that are encountered with whitening therapy. Many of these are
associated with the delivery trays, even custom-fitted ones, used in most at-home regimens.
Tray insertion and removal can lead to sensitivity and gum irritation, and tray thickness is
believed to contribute to poor compliance and development of occlusal interferences.
One alternative to the rigid delivery tray is a polyethylene strip with a hydrogen peroxide (H2O2)–
containing tooth-whitening gel (Crest® Whitestrips™, a). In this article we report preliminary
results from a randomized, placebo-controlled clinical trial that evaluated the whitening efficacy
and safety of the 2-week, twice-daily use of a peroxide tooth-whitening gel delivered on a
polyethylene film.
Materials and Methods
Study Population
Seventy adults in good general health were selected for the study. To be included, participants
had to have (1) a minimum of 16 natural teeth, including 4 maxillary anterior teeth; and (2) at
least 3 maxillary teeth gradable at Vita®,b shade A2 or darker. Patients with obvious periodontal
26
disease (as evidenced by purulent exudate, tooth mobility, or other signs), oral pathoses
requiring prompt treatment, active untreated dental caries, dentinal hypersensitivity, or who had
tetracycline stain, dental fluorosis, or atypical non uniform stain were excluded from the study.
Previous participation in a professional or home-use vital bleaching trial, participation in a
dentifrice-whitening trial in the past year, or having fixed orthodontic appliances on the anterior
teeth were further reasons for exclusion. All participants provided written informed consent and
agreed to delay any elective dentistry (including dental prophylaxis) and to refrain from using
any other than the assigned dentifrices or toothbrushes during the study.
Study Design
The study was a randomized, placebo-controlled, double-blind, parallel-group trial. Subject
eligibility and an average Vita® shade score for each participant were determined at the
screening visit (visit 1). At the baseline visit (visit 2), participants were stratified on the basis of
their screening Vita® shade average score and gender, and randomized to either the placebo or
the active treatment group with a block-randomization protocol. Baseline tooth color and safety
assessments (described below) were performed. These assessments were repeated at the end
of the 2-week treatment period (visit 3).
Treatment
The active treatment product consisted of a polyethylene film with a tooth-whitening gel
containing 5.3% H2O2, supplied as strips for anterior teeth. Polyethylene film with a placebo
tooth-whitening gel served as the control. Except for the presence of peroxide, test products
were identical in composition and packaging. Study participants applied the strips twice daily to
the maxillary anterior teeth for 30 minutes at home and brushed normally twice a day with
Crest®,a toothpaste and provided toothbrushes.
27
Efficacy Assessment
Efficacy was assessed as the change in Vita® shade tooth color between baseline and end-oftreatment visits. Up to six teeth from among the maxillary incisors and cuspids were selected at
baseline on the basis of shade (minimum Vita® shade score of A2) and access for grading. At a
minimum, the four maxillary incisor teeth were graded at baseline for each subject. The Vita®
shade guide has been used successfully in clinical studies to gauge the efficacy of tooth
whitening products.7,8 All assessments were made by a standardized, trained, and calibrated
examiner, and performed in the same operatory throughout the study. All examinations were
performed blinded as to treatment assignment.
Safety Assessment
Extensive safety evaluations were performed to establish the absence of irreversible side
effects associated with the use of the tooth-whitening gel. Assessments were performed at
baseline and at the end of treatment and included the following:
1. Oral soft-tissue (OST) examination—this consisted of a visual examination of the oral
cavity and perioral area, including gingiva (free and attached), hard and soft palate,
oropharynx/uvula,
buccal
mucosa,
tongue,
floor
of
mouth,
labial
mucosa,
mucobuccal/mucolabial folds, and lips.
2. Oral hard-tissue examination—a visual and tactile examination was performed of the
dentition and restorations.
3. Dentinal hypersensitivity—this parameter was assessed by questioning participants
about tooth hypersensitivity to thermal, air, or other stimuli.
4. Löe and Silness gingival index (GI)—the GI was an assessment of periodontal health
that evaluated the severity of gingivitis on the basis of color, consistency, and bleeding
on probing (BOP). Six gingival areas on each Ramfjord tooth (tooth Nos. 3, 9, 12, 19, 25,
and 28) were scored from 0 to 3, and an average score for each participant was derived
28
by dividing the sum of individual scores by the number of evaluable sites. Scoring criteria
were as follows: 0—normal gingiva; 1—mild inflammation (slight color changes and
edema; no BOP); 2—moderate inflammation (redness, edema, and glazing; BOP); 3—
severe inflammation (marked redness, edema, ulceration; tendency toward spontaneous
bleeding); 8—ungradable site; 9—missing tooth.
5. Silness and Löe plaque index (PI)—the PI was an assessment of the plaque deposit at
the gingival area of the tooth. Dental plaque was scored on the facial, lingual, mesial,
and distal surfaces of the Ramfjord teeth at 6 sites per tooth, in both arches (with a
maximum of 36 sites). An average PI score was obtained for each participant, by
dividing the sum of individual scores by the number of gradable sites. Scoring criteria
were as follows: 0—no plaque/debris; 1—film of plaque adherent to free gingival margin
and adjacent tooth area and seen in situ only after probing; 2—gingival area visibly
covered with a thin to moderately thick layer of plaque; 3—abundant soft matter within
the gingival pocket or on the tooth and gingival margin; 8—ungradable site; 9—missing
tooth.
Analysis
Effectiveness was determined by measuring the change in Vita® shade codes from baseline to
end of treatment for each evaluable tooth for the active group (Figures 2A and 2B). Shade
scores were ordered from 1 to 16 according to the brightness grouping recommended by the
manufacturer. Using this ranking, B-1 represented a score of “1,” while C-4 represented a score
of “16.” A decrease in Vita®shade numeric code represented an increase in tooth whiteness. All
adverse events related to OST, hard tissue, and dentinal hypersensitivity were summarized.
Analysis of covariance was used to compare the mean Vita® shade score change from baseline
between the active and placebo groups at the end of the 2-week treatment period. Baseline
Vita® shade score was included as a covariate in the model.
29
RESULTS
Demographic and Baseline
Characteristics
The peroxide-treated and placebo groups were comparable with respect to age, sex, and race
distribution (Table 1). Baseline Vita® shade scores were similar for the two treatment groups.
Scores were 8.18 (D-4 to A-3) and 8.28 (D-4 to A-3), and, on average, ranged from A-2 to C-4
and from A-2 to A-4 in the active and placebo groups, respectively. Sixty four percent of teeth
treated in the active group started at scores of C-2 or whiter.
Efficacy
Table 2 summarizes the Vita® shade scores in the 2 treatment groups at the end of the 2- week
treatment period. Data were evaluated for 33 participants in each group. After treatment with the
peroxide-containing gel, the average score declined from 8.18 at baseline to 4.55, which was a
change of –3.7 ± 0.35, representing an average increase in tooth whiteness of approximately 4
Vita® shades. By contrast, the placebo group experienced a Vita® shade score change of only –
0.87 ± 0.24. After adjustment for baseline scores, the mean difference in shade change
between the peroxide gel–treated group and placebo-treated group was –2.85 ± 0.41 (P <
0.0001).
Safety
Abnormal soft-tissue findings were noted at baseline and after completion of treatment. There
were no new notable findings, nor was there any exacerbation of baseline pathology in any soft
tissue for the 66 participants evaluated at the end of treatment. In the placebo group, one
patient had slight cervical inflammation over one tooth. After treatment with peroxide-containing
gel, one patient developed a minor superficial distal cervical lesion on one tooth and a second
patient showed a swollen papilla between two adjacent teeth. The hard-tissue examination and
dentinal hypersensitivity assessment were unremarkable.
30
Both groups experienced a
significant reduction (P < 0.0001) in gingivitis and plaque scores over the 2-week evaluation
period (Table 3). After adjusting for baseline, there were no significant differences (P > 0.70)
between the treatment groups in either the gingivitis or plaque scores after 2 weeks.
Discussion
This study demonstrates the efficacy and safety of a simple at-home tooth-whitening technique
consisting of 5.3% H2O2 gel applied to disposable polyethylene strips. Twice-daily, 30-minute
applications of the whitening strips for 2 weeks lightened discolored teeth by more than 3 Vita®
shades, compared with a change of less than 1 Vita® shade in teeth treated with placebo gel.
This treatment difference was highly significant after adjusting for baseline. Adverse effects after
treatment were minimal and were observed in less than 10% of subjects in either treatment
group. The main findings in these participants were papillary swelling, minor cervical
inflammation, and a superficial cervical lesion.
Growing public interest in whiter, brighter teeth has increased demand for tooth-whitening
procedures and products. More than 90% of dentists now offer an at-home whitening procedure,
and 50% to 60% offer an in-office technique.
9,10
Despite their proven efficacy, these systems
suffer from certain drawbacks. In-office treatments are rarely successful in just a single visit, and
3 to 5 visits are usually needed to achieve reasonable results, making this an expensive
procedure.11 Also, the higher concentrations of H2O2 (30% to 35%) used for in-office bleaching
can cause chemical trauma to gingival tissue and also hold the risk of cervical root resorption. 12
Home-whitening systems provide a relatively inexpensive way to lighten discolored teeth but
require patient compliance and discipline. The nightguard system, which requires patients to
wear a custom-fabricated tray all night or for several hours during the day to achieve optimal
results, is cumbersome and requires an average of 2 to 6 weeks of treatment. 2 Stubborn stains
may require extended treatment periods of 2 to 6 months. Patient compliance with such lengthy
31
regimens is therefore a problem; in a 6-month nightguard vital bleaching study, the rate of
compliance was only 60%.5 To encourage compliance, some offices recall patients on a weekly
basis, which is not an efficient use of office time and also adds to the cost of the procedure.
Many patients may therefore elect to have the procedure completed in the dentist’s office and
will pay the extra cost.13 Thermal tooth sensitivity and gingival irritation, two common adverse
effects that may occur in as many as two thirds of patients undergoing nightguard treatment,
have been ascribed to tray rigidity, multiple changes of the whitening solution in a 24-hour
period, soft-tissue coverage of the guard, and leakage of fluid from the guard.14 Furthermore,
the system may not be favorable for use in certain patient groups. For example, patients with
temporo-mandibular joint disorders can wear trays only during the day, and patients with
bruxism may wear through several trays over the course oftreatment.11
A strong market also exists for OTC products, despite the fact that advertised claims for the
efficacy and safety of these products remain unsubstantiated.11 Additional drawbacks of OTC
systems include lack of professional supervision and poorly adapted bleaching trays, which can
cause occlusal problems, joint and muscle pain, increased salivation, and discomfort during
sleep with extended treatment times.2,11
The treatment described here provides an attractive alternative to current at-home whitening
procedures. The polyethylene film with peroxide gel is supplied as ready-to-use strips and is
easily applied by patients. This ease of use contrasts with the nightguard system, which must be
custom fabricated, precisely fitted, and filled with the bleaching product at each use. In addition,
successful tooth lightening with the film is observed with a much shorter duration of daily wear,
and the thin film is more comfortable and better tolerated by patients. These factors favor
patient acceptance of the procedure and encourage compliance with the whitening regimen.
32
Table 1—Demographic Characteristics at Baseline
PeroxideContaining Gel
(n = 35)
Placebo Gel
(n = 35)
Overall
(n = 70)
32.3 (18-66)
33.8 (22-56)
33.0 (18-66)
Male
Female
15
20
17
18
32
38
Asian
Black
White
Hispanic
5
2
27
1
2
2
30
1
7
4
57
2
Demographic
Characteristic
Age (years)
mean range
Sex
Race
S19
Table 2—Average Shade Scores by Treatment
5.3% Peroxide Strip
Placebo Strip
Baseline
(n = 35)
End
of Treatment
(n = 33)
Change
from Baseline
(n = 33)
Baseline
(n = 35)
End
of Treatment
(n = 33)
Change
from Baseline
(n = 33)
Mean
8.18
4.55
-3.70
8.28
7.49
-0.87
Standard
Deviation
2.72
2.56
1.99
2.51
3.00
1.35
Median
7.00
3.67
-4.00
7.33
6.67
0
33
Table 3—Gingival (GI) and Plaque Index (PI) Scores at Baseline and 2 weeks
Baseline
End Of Treatment
(2 weeks)
Change
(BaselineEnd of
Treatment
)
n
Mean
SD
Range
n
Mean
SD
Range
Mean
5.3% Peroxide Strip
35
0.75
0.405
(0, 1.6)
33
0.23
0.331
(0, 1)
-0.52
Placebo Strip
35
0.65
0.436
(0, 1.5)
33
0.16
0.323
(0, 1)
-0.49
5.3% Peroxide Strip
35
0.85
0.437
(0, 1.6)
33
0.24
0.407
(0, 1)
-0.61
Placebo Strip
35
0.76
0.450
(0, 1.3)
33
0.18
0.380
(0, 1)
-0.59
GI
PI
34
REFERENCES
1. Haywood VB, Heymann HO: Nightguard vital bleaching. Quintessence Int 20:173-176,
1989.
2. Haywood VB: Current status and recommendations for dentist-prescribed, at-home tooth
whitening. Contemp Esthet 3(suppl 1):2-9, 1999.
3. Haywood VB, Leonard RH, Nelson CF, et al: Effectiveness, side effects, and long-term
status of nightguard vital bleaching. J Am Dent Assoc 125:1219-1226, 1994.
4. Matis BA, Cochran MA, Eckert G, et al: The efficacy and safety of a 10% carbamide
peroxide bleaching gel. Quintessence Int 29:555-563, 1998.
5. Haywood VB, Leonard RH, Dickinson GL: Efficacy of 6 months of nightguard vital
bleaching of tetracycline stained teeth. J Esthet Dent 9:13-19, 1997.
6. Li Y: Biological properties of peroxide-containing tooth whiteners. Food Chem Toxicol
34:887-904, 1996.
7. Croll TP, Sasa IS: Carbamide peroxide bleaching of teeth with dentinogenesis imperfecta
discoloration: report of a case. Quintessence Int 26:683-686, 1995.
8. Small BW: The application of and integration of at-home bleaching into private dental
practice. Compend Contin Educ Dent 19:810-813, 1998.
9. Christensen GJ: Bleaching teeth: practitioner trends. J Am Dent Assoc 128:16S-18S,
1997.
10. Christensen GJ: Bleaching teeth: report of a survey. 1997. J Esthet Dent 10:16-20,
1998.
11. Blankenau R, Goldstein RE, Haywood VB: The current status of vital tooth whitening
techniques. Compend Contin Educ Dent 20:781-794, 1999.
12. Barghi N: Making a clinical decision for vital tooth bleaching: at-home or in-office?
Compend Contin Educ Dent 19:831-838, 1998.
13. Nash RW: In-office bleaching system for quick esthetic change. Compend Contin Educ
Dent 20:986-1000, 1999.
14. Leonard RH: Efficacy, longevity, side effects, and patient perceptions of nightguard vital
bleaching. Compend Contin Educ Dent 19:766-781, 1998.
35
Chapter 3
Concentration and Dose Response
Clinical Trial Evaluating the Peroxide Concentration Response of a Polyethylene
strip Delivery System over 28 Day
ABSTRACT
OBJECTIVES: The research evaluated the peroxide concentration whitening response
following self-directed use of whitening strips over a 28-day period.
MATERIALS AND METHODS: A randomized, double-blind, parallel group clinical study was
conducted. 37 healthy adult volunteers were randomly assigned to one of three groups based
on tooth color at screening – 1.8% hydrogen peroxide strips (HPS), 3.3% HPS or 5.3% HPS.
Subjects applied the assigned maxillary strips twice per day for 30 minutes over 28 days. Tooth
color was evaluated at day 7, 14 & 28 from digital images of the maxillary 6 anterior teeth using
a standard method. Treatments were compared using analysis of covariance (adjusting for
baseline), or analysis of variance at a 0.05 level of significance.
RESULTS: Hydrogen peroxide at concentrations ranging from 1.8-5.3% resulted in significant
(p < 0.05) color improvement versus baseline as early as Day 7.
There was a clear
concentration-response for all color parameters (b*, L* and E*) at all timepoints, favoring the
higher concentrations.
While the concentration-whitening relationship approached a linear
response at Day 7, continued treatment resulted in incremental color improvement. All three
peroxide concentrations were well tolerated, and no subjects discontinued early due to a
treatment-related adverse event.
CLINICAL SIGNIFICANCE: Digital image analysis demonstrated a concentration gradient for
whitening response following use of a low peroxide dose strip whitening system.
36
INTRODUCTION
Discoloration of the natural dentition may occur as a result of exposure to various chemicals or
medicines, disease processes, and other factors.1 Much of this staining is intrinsic in nature, and
a likely product of the aging process that can be readily measured as increased yellowness and
decreased brightness in tooth color.2 Treatment typically involves peroxide-based vital
bleaching, sometimes in combination with other esthetic dental procedures. In practice,
peroxide-containing gels may be applied using a tray, strip or other barrier system, at-home
over time, or in-office with gingival isolation, to assure necessary contact time for peroxide
diffusion through enamel to the underlying stain.
Practiced widely since the late 1980s, vital bleaching is recognized as safe and effective. There
are several contemporary reviews that support tooth whitening using peroxide-containing gels in
combination with barrier systems.3-5 Some cases with extensive staining, from tetracycline or
other agents, have been treated daily with peroxide for several weeks or months without
significant adverse response.6,7 Post-treatment follow-up, which has now exceeded a decade in
some instances, provides further evidence of safety with vital bleaching.8,9
Peroxide concentration and contact time with tooth surfaces are recognized as playing a
prominent role in the clinical response seen with vital bleaching.10 Since the 1980s, use of
higher peroxide concentration gels has become more commonplace, in turn, lowering
recommended treatment times from several weeks to only a few days. At the extreme, very
high concentrations of hydrogen peroxide in the range of 35-38% provide a basis for tooth
whitening as an in-office procedure.11,12 Research on peroxide degradation in vivo, and in vitro
shade measurements on extracted teeth further support a relationship between peroxide
concentration and whitening.13,14
37
Although widely-accepted and plausible, there are surprisingly few peroxide concentration
ranging studies in the clinical trials literature. Such evidence is largely confined to the traybased, professional bleaching systems at hydrogen peroxide-equivalent concentrations of 37%.7,15
Concentration ranging studies provide important evidence, not only of product response, but
also of measurement validity in clinical trials applications. New clinical research was conducted
to evaluate the effects of peroxide concentration on clinical response using one of the new selfdirected strip-based bleaching systems. Digital image analysis was used to extend the dose
ranging evidence from older tray-based research to the newer strip delivery system.15
MATERIALS AND METHODS
A randomized, double-blind, parallel group clinical trial was conducted to evaluate the impact of
peroxide concentration and treatment duration on whitening effectiveness. The research was
conducted within a private dental practice located in western Tuscany, Italy. Following informed
consent, 37 healthy adult volunteers underwent vital bleaching of the maxillary anterior teeth
using a flexible polyethylene strip coated on one side with an experimental, hydrogen peroxide
bleaching gel. After balancing for baseline tooth color, subjects were randomly assigned to one
of three experimental groups: 1.8% hydrogen peroxide strips, 3.3% hydrogen peroxide strips or
5.3% hydrogen peroxide strips (The Procter & Gamble Company, Cincinnati, OH USA).
Maxillary strips carried 0.200 mg of hydrogen peroxide gel distributed uniformly across the 9.9
cm2 strip surface. In this double-blind study, treatment groups differed only in peroxide
concentration, and otherwise, were identical in appearance, aesthetics, packaging, and labeling.
Usage was twice daily for 30 minutes over a 28-day period, at-home and unsupervised. Study
participants returned for efficacy and safety evaluations at day 7, day 14, and day 28.
Efficacy and safety assessments were conducted at baseline and subsequent visits blind as to
treatment assignment. Efficacy was assessed as change in tooth color as measured from
38
standard digital images of the maxillary anterior teeth. This objective and instrumental color
measurement method had previously been used to demonstrate a peroxide concentration
response for tray-based professional bleaching systems.15 Using this method, subjects were
first positioned in a chin rest, retractors were inserted, and standard bilateral illumination of the
arch was obtained from two 150-watt lights and linear polarizers. Images were then captured
using a photographic system using a HC1000 CCD high resolution digital camera manufactured
by Fuji a Fujinon A8x12BMD, 1:2.8/12-96mm zoom lens, and a personal computer. Color
measurements were calibrated to known standards daily prior to use and hourly thereafter to
assure proper operation. Safety was assessed by interview and clinical examination at each
visit. The interview focused on tooth sensitivity or oral irritation during treatment, since these
have been recognized as the most common adverse events associated with vital bleaching.16
The clinical examination, using a standard dental light, dental mirror, and gauze, evaluated the
oral and perioral regions, including the gingiva (free and attached), hard and soft palate,
oropharynx/uvula, buccal mucosa, tongue, floor of the mouth, labial mucosa,
mucobuccal/mucolabial folds, and lips to assess any changes in oral status with treatment.
For analysis, red-green-blue values for the 6 maxillary teeth were derived with reference to
calibration standards, and then, these average values were transformed to yield CIELAB tooth
color values for b* (yellow – blue), L* (lightness), and a* (red – green).17 Change values were
calculated for any given post-baseline visit as: b* = b*visit - b*baseline, L* = L*visit - L*baseline, a* =
a*visit - a*baseline. In addition, a composite parameter, E*, was derived from the square root of
the sum of the squares of the individual L*a*b* changes. Reduction in yellowness (b*) was
selected a priori as the primary endpoint, because this parameter has been previously shown to
correlate with subjective perception of whitening following vital bleaching.18
A paired difference t-test was used to evaluate absolute color improvement (change from
baseline). Between-group efficacy comparisons were made at each time point using analysis of
39
covariance with the baseline value as the covariate. A separate model was fit for b* and L*.
Treatment comparisons for E* used analysis of variance methods. All testing was two-sided at
a 5% significance level without adjusting for multiple comparisons. Tolerability outcomes were
tabulated by treatment.
RESULTS
Of the 37 subjects randomized, one had a baseline image that was not evaluable, one had
extensive facial anterior restorations, and one had heavy, atypical extrinsic stain. Of the 34
remaining subjects, 32, 29 and 28 were present and evaluable at Days 7, 14 and 28,
respectively. This sample ranged in age from 21-66 years, with mean (SD) age of 37.2 (11.4).
Males (53%) and females (47%) were similarly represented in the population. Study subjects
exhibited considerable diversity with respect to tooth color. At baseline, b* (yellowness) ranged
from 16.2 to 22.7, L* (brightness) ranged from 66.3 to 77.2, and a* (redness) ranged from 5.9 to
9.1. Treatment groups were balanced (p > 0.18) with respect to age, gender, and tooth color at
baseline.
All three treatments resulted in significant whitening, with color improvement evident as early as
Day 7. For the primary response parameter, the Day 7 mean (SD) b* values were –0.44
(0.558), –0.86 (0.509), and –1.41 (0.690) in the 1.8%, 3.3% and 5.3% hydrogen peroxide strip
groups, respectively, with each group differing significantly from baseline (p < 0.05) at this initial
timepoint. Outcomes were generally similar for L*, as well as the composite parameter E*,
with each differing significantly (p < 0.05) from baseline at Day 7. Continued use past Day 7
resulted in incremental color improvement. This was evident for the individual parameters b*
and L*, as well as the composite parameter, E*.
Between-group comparisons generally favored the higher concentration groups (Table 1-3). At
Day 7, the 5.3% strips exhibited significant (p < 0.05) reduction in yellowness versus the other
40
two groups, while at Day 14, both the 5.3% and 3.3% groups differed significantly (p < 0.03)
from the lowest concentration 1.8% strips. These outcomes generally held (directionally or
significantly) for L*, and for the composite parameter E*. At Day 7, mean (SE) E* was 1.01
(0.204), 1.66 (0.204) and 2.30 (0.214) for the 1.8%, 3.3% and 5.3% groups, respectively. All
three treatments differed significantly (p < 0.05), with increasing concentration contributing to
greater composite color change. Results were similar over time, though by Day 28, the
composite E* for the intermediate concentration approached that seen with the higher
concentration. Mean (SE) E* was 3.23 (0.272) and 3.26 (0.246) for the 3.3% and 5.3%,
respectively, with these higher concentration strips not differing significantly (p = 0.944).
Figure 1 illustrates the concentration response for the primary whitening parameter b* over
time. (Because yellowness is removed during bleaching, negative change in b* is
representative of color improvement. The graph illustrates –b* in order to be consistent with
L*, where positive change represents improvement.) The linear concentration response is
most evident at Day 7 across the concentration ranges tested in this research. Similar results
are evident for L*, and the mathematical composite parameter E* (Figures 2-3). Overall,
twice-daily use of 5.3% strips for 14 days yielded generally similar whitening (b*, L and E*)
to the 3.3% strips used for 28 days.
Transient oral irritation represented the most common side effect associated with treatment.
Oral irritation was reported only in the lower concentration group (25% of subjects), and the
higher concentration group (36% of subjects). One subject (in the 5.3% hydrogen peroxide
group) had an aphthous ulcer during treatment. Other safety findings were generally
unremarkable. Most (75%) oral soft tissue findings were judged “mild” in severity, with only two
events (in the higher concentration group) scored as moderate. All peroxide concentrations
were well tolerated overall, and none of the study participants discontinued strip use due to a
product-related adverse event.
41
DISCUSSION
This double-blind clinical trial evaluated the effect of peroxide concentration on whitening
response following repeated daily use of a self-directed bleaching system. In this research,
hydrogen peroxide at concentrations ranging from 1.8-5.3% resulted in significant color
improvement compared to baseline. This was evident for all individual L*a*b* color parameters
measured in the study, as well as the mathematical composite parameter E*, beginning as
early as Day 7.
Extended treatment duration past Day 7 contributed to greater observed whitening response for
each of the strip concentrations. This was evident for all parameters (b*, L* and E*)
measured in this study. Such results are consistent with previous research which demonstrated
a favorable impact of treatment duration on tooth color in head-to-head testing comparing a
popular tray and strip-based system.19 Use of hydrogen peroxide under barrier conditions at
lower concentrations (~2%) is likely to require a much greater treatment duration. In this
research, the observed whitening response at Day 7 with the 5.3% strips (b*, L* and E*)
exceeded that achieved with the 1.8% strips at Day 28. Clinical implications with respect to
compliance and other factors may suggest use of higher concentrations where possible.
The research provides clear evidence of a peroxide concentration whitening response.
Whitening efficacy was greatest for the highest concentration group (5.3% hydrogen peroxide),
while the intermediate concentration group had an intermediate response. Not surprisingly, this
effect most approached linearity at the earliest time point (Day 7). At that time, adjusted mean
b* for was –1.43, –0.84, and –0.44 in the higher, intermediate and lower concentration groups,
respectively. Relative to the lowest concentration strip, this represented a 225% improvement
in whitening for the 5.3% strip (a 194% increase in concentration), and a 91% improvement in
whitening for the 3.3% strip (a 83% increase in concentration). As such, peroxide concentration
42
alone likely contributed the measured differences in response at that time point, results that are
completely consistent with the physical chemical bleaching process.
With extended treatment, the concentration response curve flattened out especially at the two
higher peroxide concentrations. At Day 28, the adjusted mean b* was 20% higher in the 5.3%
group compared to the 3.3% group (a 61% difference in concentration). While sample sizes
were small, there were no statistically significant differences in b*, L* or E* between the
higher and intermediate concentrations at Day 28. This flattening with extended treatment may
be expected in dose ranging, especially where the response substrate (intrinsic stain) is nonrenewal or slowly renewable, as it is with vital bleaching.
Despite the concentration differences (there was nearly a three-fold difference between the
lowest and highest concentration tested in this research), all three strips tested in this research
carried a low total amount of peroxide. The total amount of hydrogen peroxide on each predispensed strip ranged only from 3.6-10.6 mg. Relative to some tray-based systems, which
may deliver up to 2 grams of bleaching gel, total peroxide delivered with any of these strips was
remarkably low. This likely contributed to the low overall adverse event rate seen in this trial.
All three treatments were well tolerated, with no subjects reducing or discontinuing treatment
due to bleaching-related adverse events.
This new clinical research provides evidence of a concentration gradient for whitening response
following use of a low peroxide dose strip whitening system. As such, this may represent a first
example of concentration ranging for one of the self-directed bleaching systems. More
importantly, the research also provides evidence of the sensitivity and robustness of the
measurement method – in this instance – digital imaging. While previous concentration ranging
research was conducted in the US on tray-based systems, this work was done in Italy, in a
private dental practice using strips for peroxide delivery.15 The authors are unaware of any other
43
method (whether subjective shade assessment or objective colorimetry) that has demonstrated
similar measurement sensitivity under such diverse clinical research conditions.
Concentration ranging trials, like this one, represent one of the most complex and difficult
studies types in the clinical research arena. Research of this nature may be particularly
exemplary of the measurement sensitivity (or lack thereof) of the clinical method used in the
study. By design, the goal of this research was to distinguish both the effect of increased
peroxide concentration (three treatment groups) and increased treatment duration (three posttreatment timepoints) within the constraints and variability seen with unsupervised human
testing. Moreover, the research involved a degree of blinding, both with respect to the test
products (identical appearing peroxide-containing strips), and clinical methods (instrumental
color measurement from digital images) greater than that seen in most vital bleaching clinical
trials. Despite these complexities, the research adequately differentiated multiple
concentrations from low to high over time. With b* as an endpoint, the study demonstrated a
nearly linear concentration response relationship, with measured efficacy differences at Day 7
that reasonably modeled the real concentration differences between groups. As such, the
research provides important evidence of the validity of this method and endpoint for practicerelevant evaluation of vital bleaching technologies.
44
Tables and Figures
Table 1
Adjusted Mean b* and ANCOVA Treatment Comparisons
Table 2
Adjusted Mean L* and ANCOVA Treatment Comparisons
Table 3
Mean E* and ANOVA Treatment Comparisons
Figure 1
Peroxide Concentration on Strip and Adjusted Mean –b* at 7, 14 & 28 Days
Figure 2
Peroxide Concentration on Strip and Adjusted Mean L* at 7, 14 & 28 Days
Figure 3
Peroxide Concentration on Strip and Adjusted Mean E*at 7, 14 & 28 Days
45
Table 1
Adjusted Mean b* and ANCOVA Treatment Comparisons
Evaluable Subjects (N=34)
Visit/Group
Day 7
1.8% H2O2
3.3% H2O2
5.3% H2O2
Day 14
1.8% H2O2
3.3% H2O2
5.3% H2O2
Day 28
1.8% H2O2
3.3% H2O2
5.3% H2O2
a
Adjusted Mean
Change From
Baseline (SE)a
Two-Sided p-Value
3.3% H2O2
5.3% H2O2
-0.44 (0.181)
-0.84 (0.182)
-1.43 (0.195)
0.122
0.001
0.041
-1.02 (0.203)
-1.77 (0.245)
-1.99 (0.240)
0.026
0.006
0.525
-1.23 (0.284)
-1.91 (0.272)
-2.30 (0.251)
0.094
0.010
0.308
Means adjusted for baseline b*
46
Table 2
Adjusted Mean L* and ANCOVA Treatment Comparisons
Evaluable Subjects (N=34)
Visit/Group
Day 7
1.8% H2O2
3.3% H2O2
5.3% H2O2
Day 14
1.8% H2O2
3.3% H2O2
5.3% H2O2
Day 28
1.8% H2O2
3.3% H2O2
5.3% H2O2
a
Adjusted Mean
Change From
Baseline (SE)a
Two-Sided p-Value
3.3% H2O2
5.3% H2O2
0.74 (0.281)
1.07 (0.287)
1.31 (0.297)
0.423
0.175
0.580
1.20 (0.203)
1.32 (0.249)
1.86 (0.240)
0.717
0.051
0.140
1.28 (0.318)
2.03 (0.302)
2.15 (0.275)
0.100
0.051
0.776
Means adjusted for baseline L*
47
Table 3
Mean E* and ANOVA Treatment Comparisons
Evaluable Subjects (N=34)
Visit/Group
Day 7
1.8% H2O2
3.3% H2O2
5.3% H2O2
Day 14
1.8% H2O2
3.3% H2O2
5.3% H2O2
Day 28
1.8% H2O2
3.3% H2O2
5.3% H2O2
Mean Change
From
Baseline (SE)
Two-Sided p-Value
3.3% H2O2
5.3% H2O2
1.01 (0.204)
1.66 (0.204)
2.30 (0.214)
0.031
<0.001
0.041
1.83 (0.182)
2.39 (0.223)
2.84 (0.211)
0.061
0.001
0.158
2.00 (0.289)
3.23 (0.272)
3.26 (0.246)
0.005
0.003
0.944
48
Figure 1
49
Figure 2
50
Figure 3
51
REFERENCES
1. Watts A, Addy M. Tooth discolouration and staining: a review of the literature. Br Dent J
2001;190:309-16.
2. Odioso LL, Gibb RD, Gerlach RW. Impact of demographic, behavioral and utilization
parameters on tooth color and personal satisfaction. Compend Contin Educ Dent 2000;21:S3541.
3. Niederman R, Tantraphol MC, Slinin P, Hayes C, Conway S. Effectiveness of dentistprescribed, home-applied tooth whitening. A meta analysis. J Contemp Dent Pract 2000;15:2036.
4. Haywood VB. Current status of nightguard vital bleaching. Compend Contin Educ Dent
2000;28:S10-7.
5. Gerlach RW, Zhou X. Vital bleaching with whitening strips: Summary of clinical research on
effectiveness and tolerability. J Contemp Dent Pract 2001;2:1-16.
6. Kugel G, Aboushala A, Zhou X, Gerlach RW. Daily use of whitening strips on tetracyclinestained teeth: comparative results after 2 months. Compend Contin Educ Dent 2002;23:29-34.
7. Matis BA, Wang Y, Jiang T, Eckert GJ. Extended at-home bleaching of tetracycline-stained
teeth with different concentrations of carbamide peroxide. Quintessence Int 2002;33:645-55.
8. Ritter AV, Leonard RH Jr, St Georges AJ, Caplan DJ, Haywood VB. Safety and stability of
nightguard vital bleaching: 9 to 12 years post-treatment. J Esthet Restor Dent 2002;14:275-85.
9. Leonard RH Jr, Van Haywood B, Caplan DJ, Tart ND. Nightguard vital bleaching of
tetracycline-stained teeth: 90 months post treatment. J Esthet Restor Dent. 2003;15:142-52.
10. Matis BA. Tray whitening: what the evidence shows. Compend Contin Educ Dent
2003;24:354-62.
11. Gallagher A, Maggio B, Bowman J, Borden L, Mason S, Felix H. Clinical study to compare
two in-office (chairside) whitening systems. J Clin Dent 2002;13:219-24.
12. Papathanasiou A, Kastali S, Perry RD, Kugel G. Clinical evaluation of a 35% hydrogen
peroxide in-office whitening system. Compend Contin Educ Dent 2002;23:335-44.
13. Matis BA, Yousef M, Cochran MA, Eckert GJ. Degradation of bleaching gels in vivo as a
function of tray design and carbamide peroxide concentration. Oper Dent 2002;27:12-8.
14. Leonard RH, Sharma A, Haywood VB. Use of different concentrations of carbamide
peroxide for bleaching teeth: an in vitro study. Quintessence Int 1998;29:503-7.
15. Gerlach RW, Gibb RD, Sagel PA: A randomized clinical trial comparing a novel 5.3%
hydrogen peroxide bleaching strip to 10%, 15% and 20% carbamide peroxide tray-based
bleaching systems. Compend Contin Educ Dent 2000;21:S22-28.
16. Leonard RH, Haywood VB, Phillips C. Risk factors for developing tooth sensitivity and
gingival irritation associated with nightguard vital bleaching. Quintessence Int 1997;28:527-34.
17. Commission Internationale de L’Eclairage: Recommendations on uniform color spaces.
Color difference equations. Psychometric color terms. Suppl 2 to CIE pub 15 (E-13.1)1971/(TC1.3), Paris, France: Bureau Central de la CIE, 1978.
18. Gerlach RW, Barker ML, Sagel PA. Objective and subjective whitening response of two
self-directed bleaching systems. Am J Dent 2002;15:7-12A.
19. Karpinia KA, Magnusson I, Sagel PA, Zhou X, Gerlach RW. Vital bleaching with two athome professional systems. Am J Dent 2002;15:13-18A.
52
Chapter 4
Light activated Tooth Whitening
Clinical Evaluation of a 35% Hydrogen Peroxide In-Office Whitening System
ABSTRACT
This study evaluated the effectiveness of light-curing (heat conversion) vs no light-curing (no
heat conversion) of a 35% hydrogen peroxide in-office tooth whitening system. Twenty patients
with sound medical history (without tooth sensitivity) participated in this randomized, parallel
clinical evaluation. Only six maxillary anterior teeth with discoloration and a tooth shade of A3 or
darker were selected. Patients received a complete prophylaxis and were evaluated for initial
(baseline) shade by three independent evaluators, precalibrated at 85% rater reliability in
determining shades before the experiment began. Participants received a 20-minute chairside
whitening treatment with a 35% hydrogen peroxide agent using a reflective resin barrier for
gingival isolation. During the whitening treatment, the 35% hydrogen peroxide agent was light
activated with a halogen curing light on teeth Nos. 6 through 8 (Group I), but was not lightactivated on teeth Nos. 9 through 11 (Group II). All patients returned 24 hours after the
whitening application for shade evaluation. Although there were isolated instances (7 out of 20
patients) of greater degrees of lightening in the light-curing group, there was no statistically
significant difference using the Mann-Whitney U test (P > .05). This study indicates that lightcuring is optional with this 35% tooth whitening system.
53
Learning Objectives
After reading this article, the reader should be able to:
describe an in-office whitening technique using 35% hydrogen peroxide.
discuss tooth color modifications produced using a 35% hydrogen peroxide.
recognize the effectiveness of tooth color modifications produced with 35% hydrogen
peroxide in-office technique.
Tooth whitening has become one of the most popular esthetic dental procedures. The
management of the discolored dentition is not new to the dental profession—it was first reported
1
in 1877. Whitening offers a conservative, simplified, and economical approach to changing the
color of one’s teeth. Candidates for whitening include patients whose teeth have been stained
over time by aging, chromogenic foods, endodontic treatment, tetracycline use, and smoking or
the use of other tobacco products.
2
Acceptable whitening techniques include the in-office procedure, the dentist-prescribed homeapplied technique, or a combination of the two. Recently, whitening strips have been introduced
3
as an alternative whitening method. In the 1970s, vital tooth whitening was being performed
with in-office treatments using different concentrations of liquid hydrogen peroxide solutions and
4
(sometimes) a heat lamp. In 1989, the first article on nightguard vital bleaching using
carbamide peroxide was published by Haywood and Heymann after evaluation at the University
5
of North Carolina. Currently, the in-office whitening technique uses a 15% to 35% hydrogen
peroxide whitening agent (heated or nonheated); the dentist-prescribed home-applied technique
most commonly uses a 10% to 15% carbamide peroxide gel.
The advantage of the in-office procedure is that it does not require patient compliance and
results may be seen immediately. The disadvantage is the chair time, cost to the patient, and
the possibility of multiple visits. A light-activated chairside whitening system has the potential
advantages of taking less time and providing quicker results.
54
The purpose of this study was to evaluate:
1.
The effectiveness of a 35% hydrogen peroxide in-office system
®
®,a
®,a
(Opalescence Xtra
and OpalDam
) in tooth color modifications.
2.
The effect of light when compared to no-light activation (light-to-heat
activator and light-to-nonheated activator).
3.
The incidence of soft tissue irritation related to the active whitening
chemical, hydrogen peroxide.
4.
Patient responses to the whitening treatment.
METHODS AND MATERIALS
Before participating in this blinded, parallel tooth whitening study, all patients were
asked to sign an informed consent form. Both the form and the research protocol were reviewed
and approved by the Human Investigational Review Committee at Tufts University. A total of 20
patients (with no medically compromised history or tooth sensitivity) were recruited from the
Tufts University dental clinic to participate in this randomized, parallel clinical evaluation. The
criteria used to recruit participants for this investigation included:
No active caries.
18 years of age or older.
Maxillary and mandibular teeth with the same color.
The exclusion criteria were:
Intrinsic dental staining (ie, tetracycline or fluorosis).
Nonvital teeth.
Patients that had previous tooth whitening procedures.
Extended composite restorations at the teeth that would be included in
this study.
55
Only 6 maxillary anterior teeth with minor uniform staining or discoloration with a shade no
lighter than A3 were selected. The six mandibular anterior and contralateral maxillary, non–lightcured teeth were used as the control group.
At the initial appointment, all necessary consent forms were signed before any treatment was
rendered. Then, a thorough clinical and medical evaluation was taken for each patient. All
patients received a complete oral prophylaxis (cleaning and polishing) 2 weeks before beginning
the whitening process. At the next appointment, all of the subjects underwent a baseline
periodontal evaluation, which included color, size, shape, and consistency of the involved
gingival tissue. Each patient was evaluated for initial (baseline) shade by three independent
evaluators. The evaluators consisted of the subject, the dentist treating the subject, and a
second dentist. All evaluators were calibrated at 85% rater reliability in determining shades
before the onset of this project. A consensus method (two of the three evaluators) was used
to record the shades of the 6 test anterior maxillary teeth and 6 lower anterior teeth as
the control group. Shades were assessed using the Standard Vita
Shade Guideb. All
shade measurements were recorded at baseline and an initial photograph was taken of the
maxillary and mandibular teeth.
At this appointment, the 20 participants received a 20-minute chairside whitening treatment with
a 35% hydrogen peroxide whitening agent (Opalescence Xtra), using OpalDam for gingival
isolation. Before the hydrogen peroxide application, all teeth were cleaned using pumice and a
slow-speed rotary brush/prophy cup. Teeth Nos. 6 through 11 were whitened using the 35%
hydrogen peroxide whitening agent, but only teeth Nos. 6 through 8 were light activated with a
curing light. A questionnaire was provided to the patients for recording any comments. All
participants were able to contact any of the principle investigators if any side effects such
as tooth sensitivity, gum tissue irritation, or bad taste were experienced.
All patients were required to return 24 hours after the day of the second appointment for
a recall appointment. A final periodontal evaluation was taken for all patients, which
consisted of visual gingival recordings using standardized Löe and Silness Gingival Index:
56
0 = No inflammation
1 = Slight inflammation
2 = Moderate inflammation
3 = Severe inflammation
In addition, recordings of loss of sensation, change in gingival texture, spontaneous bleeding,
and the sloughing of gingival tissue were noted. A final shade was then selected and a final
intraoral photograph was taken at the 24-hour recall appointment.
Data (degree of color change from baseline) were analyzed using statistical tests to determine
the significance of the light activation when using the 35% hydrogen peroxide tooth whitening
agent.
RESULTS
The 35% hydrogen peroxide in-office tooth whitening system was effective in lightening teeth.
However, the purpose of this study was to evaluate the effectiveness of light-curing vs no lightcuring of this whitening system. Although there were isolated instances (7 out of 20 patients) of
greater degrees of lightening in the light-curing group (median for Group I was 7.21 and Group
II was 6.78) (Table 1), there was no statistical significant difference using the Mann-Whitney U
test (P > .05). Both whitening protocols were effective in the lightening of teeth with no adverse
effects. All shade evaluations using the Vita
Shade Guide were recorded with the guide
arranged in value order, where they are assigned a number from 1 through 16. This order is
shown at the bottom of Table 1.
Patients were given questionnaires to record tooth sensitivity, gingival irritation, bad taste, and
noticeable shade change. One patient experienced slight tooth sensitivity (only at one tooth) at
the end of the whitening procedure, which subsided before the 24-hour recall visit. No bad taste
and no gingival irritation were reported and OpalDam
appeared to be effective in isolating the
tissues against any caustic behavior. All participants in the study expressed satisfaction with the
whitening process and the results (Table 2).
57
DISCUSSION
Traditionally, in-office whitening products have been used to give a patient a head start in the
whitening process, to touch-up postwhitening cases if they should regress in shade, and to
6
function solely as a whitening product. Opalescence
Xtra
is a commonly used 35%
hydrogen peroxide tooth whitening agent for in-office treatment. After gingival isolation with
OpalDam , the whitening material was applied to each facial enamel surface on the six
maxillary anterior teeth, but was light-cured only on teeth Nos. 6 through 8. This light-activated
material is contained in a carotene base to absorb light, providing an increased whitening
7
effect. The results of this study revealed that the use of the halogen light improved the
effectiveness of the whitening material in some cases. However, in those cases, the difference
between light-cured vs non–light-cured teeth was 1 to 3 shades, which was not noticeable to the
®
patients. Shade evaluation determined Vita shade B1 for teeth Nos. 6 through 8 (light-cured)
and A1 for teeth Nos. 9 through 11 (non–light-cured).
As stated earlier, the purpose of this study was to determine if the use of a light in the in-office
whitening process would increase the effect of whitening on the teeth. Of the 20 patients in this
study, 7 patients experienced an increase in lightening of the split arch protocol. The increase
was an average lightened increase of 1.714 shades as compared to the non–light-cured side.
This was not a significant clinical change. Any shade difference as noted by the light-activated
side was most likely a result of dehydration resulting from heat generated by the halogen curing
light. Statistically, there was no significant difference between the light-activated side when
compared to non–light-activated side.
The results contradict other studies, which have indicated that light activation causes an
increased whitening effect as used with hydrogen peroxide whitening agents.
8,9
Based on the
Clinical Research Associates’ report, the use of a curing light in addition to the manufacturerrecommended exposure times, does not produce sufficient heat generation was to significantly
58
increase the breakdown of H2O2.
10
It is this activation of H2O2 that results in the increased
whitening effect. A transient whitening effect may be the result of dehydration. To potentiate the
effect of H2O2, high temperatures must be reached, which could potentially cause damage to
the tooth. This report also states that Opalescence
Xtra
experiences a relatively low rate
increase in H2O2 even when temperatures are raised as high as 100° C.
10
This would also
support our findings that the addition of light does not increase the effect of the whitening
process.
CONCLUSION
This study evaluated the effectiveness of light-curing vs no light-curing of a 35% hydrogen
peroxide in-office tooth whitening system. Tweny patients with sound medical history (without
tooth sensitivity) participated in this randomized, parallel clinical evaluation. The outcome of this
study leads to the conclusion that the use of a halogen curing light to increase the activation of
35% hydrogen peroxide is of no benefit to the dentist or the patient.
59
Table 1
Tooth Color Modifications as Ascertained by The Consensus Method
Subject
Light Cured)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
Initial
Final (Light Cured)
Final (No
A3
A3
A3.5
A3
A3
D3
A3
D3
C3
A3
A3
A3
A3
D3
A3
A3
D3
A3
A3
A3
B1
A1
A2
A1
A1
B1
A1
A1
C1
A2
A1
A2
D2
A1
D2
A1
A1
B1
D2
B1
A1
A2
A2
A1
D2
A1
A1
A1
C1
A2
A1
A2
D2
A2
D2
A1
A1
A1
A2
B1
(8)
(7)
(7)
(7)
(7)
(9)
(7)
(8)
(8)
(4)
(7)
(4)
(5)
(8)
(5)
(7)
(8)
(8)
(5)
(8)
(7)
(4)
(7)
(7)
(5)
(8)
(7)
(8)
(8)
(4)
(7)
(4)
(5)
(5)
(5)
(7)
(8)
(7)
(4)
(8)
Totals: Group I:137, Group II:125. Median Group I: 7.21 Median Group II: 6.78
The numbers in parentheses show how many shade changes were accomplished with the use
®
®
of Opalescence Xtra during the study, from the initial to the final appointment.
®
Vita Shade Guide arranged in value order:
B1
A1
B2
1
2
3
D2
A2
C1
C2
D4
A3
4
5
6
7
8
9
D3
10
B3
11
A3.5
12
B4
13
C3
14
A4
C4
15
Table 2—Tooth Sensitivity, Gingival Irritation, Bad Taste, and Noticeable
Shade Change Evaluation by Each Subject in the Exit Questionnaire
60
16
Subject
Tooth Sensitivity
Gingival Irritation
Bad Taste
Noticeable
1
No
No
No
Yes
2
No
No
No
Yes
3
No
No
No
Yes
4
No
No
No
Yes
5
No
No
No
Yes
6
No
No
No
Yes
7
No
No
No
Yes
8
No
No
No
Yes
9
No
No
No
Yes
10
No
No
No
Yes
11
Yes
No
No
Yes
12
No
No
No
Yes
13
No
No
No
Yes
14
No
No
No
Yes
15
No
No
No
Yes
16
No
No
No
Yes
17
No
No
No
Yes
18
No
No
No
Yes
19
No
No
No
Yes
20
No
No
No
Yes
Shade Change
61
PRODUCT REFERENCES
a
Ultradent Products, Inc., South Jordan, UT 84095; (800) 552-5512
b
Vita Zahnfabrik, Germany, distributed in US by Vident, Brea, CA 92621; (800) 828-3839).
REFERENCES
1. Fasanaro TS: Bleaching teeth: history, chemicals and methods used for common tooth
discoloration. J Esthet Dent 4: 71-78, 1992.
2. Kugel G: Nontray whitening. Compend Contin Educ Dent 21(6):524-528, 2000.
3. Kugel G, Kastali S: Tooth whitening eficacy and safety: randomized and control clinical trial.
Compend Contin Educ Dent 21(Suppl 28): 2000.
4. Nathanson D: Vital bleaching sensitivity and pulpal considerations. J Am Dent Assoc
128(Suppl):41S-44S, 1997.
5. Haywood VB, Heymann HO: Nightguard vital bleaching. Quintessence Int 20(3):173-176,
1989.
6. Kugel G, Perry RD, Hoang E, et al: Effective tooth bleaching in 5 days: using a combined inoffice and at-home bleaching system. Compend Contin Educ Dent 18(4):378-383, 1997.
7. Gultz J, Kaim J, Scherer W, et al: Two in-office bleaching systems: a scanning electron
microscope study. Compend Contin Educ Dent 20(10):965-970, 1999.
8. Li Y, Cartwright S, Lezama M, et al: Effect of light application on an in-office bleaching gel
[abstract]. J Dent Research 80(147), 2001. Abstract 895.
9. Tavares M, Goodson JM, Stutz J, et al: A randomized single blind clinical trial of tooth
whitening with peroxide and light [abstract]. J Dent Research 80(182):2001. Abstract 1171.
10. CRA Newsletter August, 2000.
62
CHAPTER 5
CHEMICAL VS LIGHT ACTIVATED TOOTH WHITENING
Clinical Evaluation of Chemical and Light-Activated Tooth Whitening Systems
ABSTRACT
BACKGROUND
Tooth whitening has become one of the most popular of dental treatments. There are many
options available. The paper attempts to compare the efficacy of two in-office whitening
systems.
METHODS
In this split-arch, randomized, parallel, blinded clinical evaluation six maxillary anterior teeth
(N=60) A-2 or darker were selected using the value order Vita Shade Guide. Patients received
one-hour light-activated chairside treatment using 15% H2O2 teeth 6-8 (Group I), teeth 9-11
received a 38% H2O2 system for 1 hr without a light (Group II). Before and after treatment
images were taken. L*, a* and b* and Vita shades were measured. Patients returned after 2
weeks for final shade evaluation.
RESULTS
Both in-office tooth whitening systems were effective. Group I averaged 5.9 ± 2.5 and Group II
3.97 ± 2.33 shade changes immediately after treatment. At the 2-week recall, Group I scored an
average of 4.6 ± 2.14 and Group II 4.6 7± 2.3 shade changes, compared to the pre-bleaching
shades. A paired sample t-test revealed statistically significant difference (p<0.0001) between
Groups I and II immediately after bleaching, with Group I performing better. At the 2-week recall,
however, only Group I showed a significant rebound (p=0.0002). At the completion of the study,
there was no significant difference between Groups I and II (p=0.7826).
63
CONCLUSION
This study indicated that both chairside tooth whitening systems are effective and that no
statistically significant differences were observed over the 2-week period of observation.
CLINICAL IMPLICATIONS Both systems were effective in whitening teeth. The use of light did
not demonstrate an increase in the effectiveness of Britesmile after a two-week recall.
INTRODUCTION
Technological advances in dentistry make it possible for the practitioner to deliver the highest
level of care in an efficient and often economical way. With the introduction of light activated
devices such as Plasma arc, Light Emitting Diodes (LED), Argon lasers, metal halide and
xenon-halogen lights, being promoted as “the future of dentistry,” dental manufacturers have
helped create a public awareness and demand for the so-called: “ Light enhanced tooth
whitening systems”.
In 2002 one article and more recently two papers were published evaluating the efficacy of light
activated bleaching agents. One study reported positive results1, whereas the other articles
concluded the opposite 2,3. Reviews of these articles were either in support 4 or discredited the
findings5. It is apparent that the dental profession needs more evidence in order to provide for
better and more efficient treatment. The lack of knowledge is to the detriment of the dentist and
patient alike. The need for more knowledge becomes even more important as manufacturers
inundate the dental profession with advertisements emphasizing that light activated tooth
whitening is “the state of the art” and should be part of the armamentarium of the “up to date”
dental office.
Bleaching is the most conservative treatment for discolored teeth when compared to resin
bonded composites, porcelain veneers or crowns. It offers a simple and economical approach to
changing the color of teeth. Success of the treatment depends on a careful diagnosis by the
64
practitioner. Candidates for whitening procedures include patients whose teeth are stained by
aging, chromogenic foods, endodontic treatment, tetracycline use and smoking or use of other
tobacco products.
Acceptable tooth whitening techniques include the in-office technique, dentist-prescribed homeapplied technique, or a combination of the two. The use of hydrogen peroxide (H202) for
bleaching teeth dates back to 1995 6. To reduce treatment time, clinicians attempted to
accelerate the degradation of H202 by heat or light. In 1970, Cohen and Parkins introduced a
technique for bleaching discolored teeth, such as tetracycline stained-teeth, using hydrogen
peroxide and a hand-held heating source 7.
Most clinicians know that hydrogen peroxide is a bleaching agent that can attain a desired
whitening effect. Bleaching can also be accomplished with Carbamide Peroxide, a lower
concentration of hydrogen peroxide and urea, which breaks down to 3.6% hydrogen peroxide
8,9
.The degree of whitening correlates directly with the amount of contact time and concentration
of the active ingredient, the pH and viscosity 9. The side effects are usually diminished when
lower concentrations are used.
The in-office bleaching treatment using hydrogen peroxide and an accelerating source (heat or
light) were predominant until 1989 when Haywood published the first article on nightguard vital
bleaching using carbamide peroxide 10. Currently, the in-office bleaching technique employs a
15 - 40% hydrogen peroxide bleaching agent (heat activated or not), while the dentist
prescribed home-applied technique most commonly uses a 10 - 15% carbamide peroxide gel.
The advantages of an in-office procedure are twofold. It does not require patient compliance
and immediate results can be accomplished.
The disadvantages are the chair side time
involved and the cost to the patient, as the procedure usually requires multiple visits. Lightactivated chair side bleaching systems potentially offer the benefit of being less time-consuming
while producing faster results.
The introduction of very high intensity Plasma Arc lights and Argon Lasers meets the need of an
ever increasing demand for whiter teeth. Research in vitro has demonstrated that the use of
65
laser-activated hydrogen peroxide did not produce any perceivable color change 11. Another
recent in vitro study, and one which should be of concern to the practitioner, has shown that the
use of these intense lights does elevate temperature of the bleaching material and as a result
caused an increase in intrapulpal temperature. This may have an impact on post bleaching
tooth sensitivity and pulpal health 12.
The efficacy of a bleaching treatment can be determined through first or second evaluators or
various technical methods. The use of a shade guide, colorimeter, or computer digitization to
measure color change over time has been currently included in clinical trials to assure efficacy
assessment 13, 14, 15.
The purpose of this study was to compare the efficacy of color changes of two in-office tooth
whitening systems, Brite Smile, a 15% Hydrogen peroxide system
a
and Opalescence Xtra
Boost, a 38% Hydrogen Peroxide system b. In addition, feed back from the participants allowed
for an evaluation of their satisfaction with the results of the treatment and the occurrence of
sensitivity during and after the bleaching treatment.
MATERIALS AND METHODS
Ten patients with no medical contraindications to treatment and an absence of tooth sensitivity
were asked to participate in this split-arch, randomized, parallel, blinded clinical evaluation. Only
six to eight upper anterior teeth with minor uniform intrinsic staining or discoloration with a
shade no lighter than A-3 were selected. The six lower anterior teeth and contra lateral upper
incisors were used as control groups.
All patients had received a prophylaxis (cleaning and polishing) less than 3 months before
starting the experiment. Each patient was evaluated for initial (baseline) shade by two
evaluators. The evaluators consisted of the dentist treating the subject and a second dentist.
Both evaluators were calibrated at 85% rater reliability in determining shades before the onset
of this project. Calibration was conducted pre and post study to ensure inter and intra rater
reliability.
66
At the initial appointment shades were assessed using a Standard Vita Shade Guide c. All
shade measurements were recorded at baseline and an initial photograph was taken of the
upper and lower teeth.
At the same appointment the patient received a one-hour chair side bleaching treatment for
teeth 5-8 using Brite Smile according to manufacturer’s recommendations; 3 applications of 20
minutes each in one visit. Opal Dam b was used for gingival isolation. Teeth 9-12 were isolated
from the Brite Smile material and light source during treatment by means of a custom made poly
vinylsiloxane (PVS) block. Teeth were also kept moist using wet gauze under the PVS block.
Upon completion, teeth 5-8 were isolated as descrived above and teeth # 9-12 were treated with
Opalescence Xtra Boost without the use of a curing light (3 applications of 20 minutes each in
one visit), following the manufacturer’s recommendations. Three measurements were recorded
from each side before and immediately after treatment. In addition 35mm transparencies, as
well as digital photos were taken before and after treatment.
All patients were scheduled to return 2 weeks after the day of the tooth whitening treatment for
a recall appointment. Once more post bleaching records by means of transparencies and digital
photography were taken. In addition a determination of the final shade was made. As a service
to the patient the mandibular teeth were whitened after final recording at the end of the study
using Opalescence 10% carbamide peroxide take-home system. b
A. Efficacy Assessment
The efficacy of the whitening system was evaluated with the use of a Digital Imaging Camera d,
a 35 mm camera e and Standard Vita Shade Guidec15,16.
The Olympus C2500L high resolution digital camera is utilized for sampling. To ensure proper
color analysis an extended procedure of sampling nine locations on the central incisor, lateral
incisors of the maxillary and mandibular arches was completed. This data is then averaged to
find a mean color and standard deviation of color on each tooth. A Gaussian blur filter was
67
applied during post processing which does an averaging of color over the digitally sampled
photo. All digital images were then analyzed to yield L*, a* and b* data 15.
All individuals are located in the same position in a single operatory with the camera positioned
9 inches and perpendicular from the tooth surface of the left central incisor. Patients are
presented edge to edge with retractors and asked to touch the tip of their tongue to their soft
palate. This allows light to readily pass through the tooth surface and reduce reflectance from
their tongue. A polarized filter is used on the camera to reduce the gloss that occurs from the
flash further ensuring the reduction of hot spots and increase consistent color accuracy. The
camera flash is used to ensure the consistency of light source due to its great influence on value
data. The camera is plugged in to a 120-volt source to ensure no fluctuation of flash intensity
between subjects and maintain stability of the light source.
A Standard Vita Shade Guide, arranged in order of value, was used for subjective evaluation of
the shades. Furthermore, 35mm transparencies were taken as part of the shade evaluation
protocol.
Each participant was asked to brush with water and an extra-soft toothbrush, according to Brite
Smile recommendations, to remove any debris that could interfere with shade evaluation and
photography. To standardize the photography, cheek retractors were used to retract the cheeks
and lips and the patient was instructed to line-up the lower incisal edges with the upper front
teeth. Additional photos were taken positioning the baseline shade tab next to the teeth to be
evaluated. All digital photos and analysis were performed by a blinded evaluator.
B. Safety Assessment
This clinical study assessed the efficacy and patient tolerance of two different in-office tooth
whitening systems after a single visit one-hour application. Clinical safety data information
indicated that the use of these systems, when used according to the protocol specified in this
clinical trial, did not present any undue risks to the participants.
68
This was a randomized, blinded, parallel group study with 10 healthy participants, which
approved by the Institutional Review Board of the University where the study was conducted.
Subjects that met inclusion criteria were asked to report whether they had any teeth that were
sensitive. During the initial visit an informed consent form and an explanation of the eligibility
criteria were presented. The health of the oral soft tissues was examined and recorded and a
shade determination made. Photography as described previously was also done at this visit.
Both whitening systems were used for each patient. The Brite Smile System for teeth #5-8 and
Opalescence Xtra Boost for teeth # 9-12. The application lasted for 60 minutes, according to the
protocol and instructions provided by the manufacturers. An evaluation of the oral soft tissues,
tooth sensitivity and change in shade was completed after the tooth whitening treatment and
two weeks after application. The mandibular teeth were whitened after the end of the study
using Opalescence, a 10% carbamide peroxide tray-delivered home bleaching system.
Safety and comfort was determined by an absence of irreversible effects associated with the
use of the systems and included assessment of oral soft tissues and the degree of tooth
hypersensitivity. Oral soft tissue examination was conducted visually utilizing a standard dental
light, dental mirror and gauze. Abnormal soft tissue findings were noted after the tooth whitening
treatment had been completed.
The Brite Smile System consists of a 15% hydrogen peroxide gel, Opalescence Xtra Boost of
38% hydrogen peroxide gel and Opalescence is 10% carbamide peroxide. All three whitening
systems have undergone previous clinical safety testing
17,18
. Two types of adverse reactions
have been reported, i.e. oral soft tissue irritation and tooth sensitivity 17,18. The occurrence of
these reactions were carefully evaluated and recorded following completion of the bleaching
treatment.
RESULTS
During the in-office treatment, soft tissue irritation was usually avoided with the appropriate
placement of a gingival isolation gel recommended and included in each in-office tooth
69
whitening system. Soft tissue irritation was typically of mild severity and was usually observed at
the gingival margin. The irritation resolved while the subject were still undergoing tooth
whitening treatment or within 1-3 days after discontinuation of use.
Baseline values were
confirmed using the lower teeth as a control group. Tooth sensitivity was experienced and
recorded and was of mild severity, which resolved usually within 1-2 days after discontinuation
of the product.
A. Shade Guide Evaluation
Both in-office whitening systems were effective in making teeth lighter. The Vita Shade Guide
scores from the lightest to the darkest shade in numeric code order (Table I). The recorded
shades utilizing the Vita Shade Guide showed that Brite Smile averaged 5.9  2.5 and
Opalescence Xtra Boost averaged 3.97  2.33 shade changes immediately after the whitening
procedure. At the 2 week recall, Brite Smile’s effect was reduced to an average of 4.6  2.14
while Opalescence Xtra Boost increased to 4.67  2.3 shade changes (Table II and Table III).
Patients were given a questionnaire to record tooth sensitivity, gingival irritation, bad taste and
noticeable shade changes. Six patients experienced tooth sensitivity in which four patients
reported sensitivity in both sides; one patient reported sensitivity on the Britesmile side and the
other patient reported sensitivity on the Opalescence Xtra Boost side. One patient reported
gingival irritation at the end of the whitening procedure, observed in both sides, which subsided
in less than 24 hour. No bad taste was reported and all participants in the study expressed
satisfaction with the whitening process and the results.
B. Digital Photography Evaluation
The digital photography revealed the following results (Table IV): Whitening benefit
is defined as tooth color change from baseline assessed by the digital imaging
measurements b* (yellow – blue), L* (light – dark), and a* (red – green). For a given
70
post-baseline visit: b* = b*visit - b*baseline, L* = L*visit - L* baseline, a* = a* visit
- a* baseline.
Preoperative vs. Immediate Post Bleaching
There was a significant difference in b (p=0.01) for the BriteSmile compared to
Opalescence Xtra Boost immediately post bleaching, while Opalescence Xtra Boost had a
significant decrease in the a score (p=0.01) post bleaching compared to BriteSmile. The
other values showed no significant differences between the two products. The data
indicates that BriteSmile had a greater whitening effect when evaluated immediately post
bleaching based on L* and b* which are directly linked to bleached dentition (citation). Both
products show statistical difference (P=.01) before and after treatment for L* and b*.
Immediate Postoperative vs. 2 Weeks Post Bleaching
BriteSmile demonstrated a significant rebound by a positive b value (p<0.001). This signifies
that the BriteSmile subjects had an increase in yellow coloration. This may be attributed to
dehydration of the tooth from the application of the light or it may be a normal response of
rebound.
The Opalescence Xtra Boost may not have displayed this rebound due to the
prolonged activity of the bleaching material after the sample readings were taken immediately
post bleaching. The a* values showed no statistical change in either group. The L* displayed no
significant change for the Britesmile yet the Ultra Boost showed the mean L* increase in value
by 1.7 units.
Preoperative vs. 2 Weeks Post Bleaching (Overall)
The data indicates that both BriteSmile and Opalescence Xtra Boost whitened teeth to
statistically significant level (P=.01) for L* 3.6 (BriteSmile), 3.8 (Xtra Boost) and b* -6.0
(BriteSmile), -5.0 (Xtra Boost) equivalent to between 3 and 6 shades as determined on a Vita
shade guide (cite). The two whitening systems were not statistically significantly different from
pre-bleaching to two weeks post bleaching. All patients reported to be satisfied with the results
71
at the end of the treatment. Sensitivity appeared not to be an issue and none of the patients
expressed concern or complained about this side effect.
DISCUSSION
The question as to whether to use light activation during chair side bleaching or not and the
purported benefits are still an issue of debate. The use of two blinded and calibrated evaluators
in this study set it apart it from other publications evaluating this technology 1. In this study, the
direct in-office whitening system using a gas plasma light for three twenty minute applications in
conjunction with 15%hydrogen peroxide gel, was compared to a chemically activated system
using 38% hydrogen peroxide. Either heat or a chemical reaction can cause the peroxide to
break down into oxygen radicals and water more quickly. The more oxygen is liberated, the
more oxydation can take place. In the absence of heat, lowering the pH is one such mechanism,
by which, when Opal Xtra Boost is chemically activated, oxygen and water are liberated.
The clinical observation using a value ordered Vita Shade Guide was confirmed using digital
analysis of L*, a*, b* color values
15
. In addition the digital camera was calibrated for each
image. Unlike other studies, the teeth of the one side were kept moist during bleaching, thus
minimizing the effect of dehydration that can occur while the other lateral side was being
bleached. This might explain why our data does not show the dramatic results reported in
another paper 1.
The use of light activation using the Britesmile in-office bleaching system resulted in increased
whitening compared to Opalescence Xtra Boost, which does not require light activation. This is
believed to be the result of dehydration of the tooth caused by the generation of heat from the
curing light 2. This increase, however, was of temporary nature, as after 2 weeks no differences
were recorded between the two systems. The initial improvement in tooth whitening observed
with the Britesmile system is therefore most probably the result of dehydration. The Britesmile
system incorporates the use of “hydrogel” and it has been suggested that this hydrogel (the
company does not volunteer the composition), prevents the teeth from dehydrating. Prevention
72
of dehydration of any light activated in office bleaching procedure is virtually impossible,
however.
Opalescence Xtra Boost did not demonstrate significant rebound and actually showed a slight
improvement after 2 weeks. This is possibly due to the fact that there was less dehydration
since no light and /or heat are required to activate the system. Furthermore, it is also possible
that a prolonged exposure and activity after the gel took place after it was rinsed off. It is
believed that continued oxydation can take place over time with the chemically activated
system, as activated hydrogen peroxide in water is able to penetrate deeper and/or reside in the
tooth longer, since it is not driven out by evaporation due the application of heat.
It is reasonable to conclude that with the increase in temperature, dehydration did occur, which
was subsequently followed by rehydration. Therefore in spite of the initial perception that an
increase in whitening took place, the 2-week post-operative evaluation did not demonstrate a
difference, which was confirmed by an absence of a statically significant difference between the
two materials.
We realize that this study represents a small sample size. This was due in part to the difficulty in
obtaining a Bristesmile unit. More independent research evaluating a larger sample size is
recommended. Factors such as cost of the light, operatory space, and maintenance should be
entered in the equation when purchasing a light. Advantages and disadvantages of light
activated whitening systems should be carefully considered.
CONCLUSIONS
1. BriteSmile and Opalescence Xtra Boost whitened teeth between 3 and 6 shades and
were not statistically significantly different from pre-bleaching to two weeks post
bleaching,
2. BriteSmile had a greater whitening effect when evaluated immediately post bleaching,
but demonstrated a significant rebound of the b score (p<0.001). This may be attributed
73
to dehydration of the tooth from the application of the light (heat) or it may be a normal
response of rebound,
3. Opalescence Xtra Boost did not display this rebound effect, probably due to a more
prolonged activity of the bleaching material after the sample readings were taken
immediately post bleaching,
4. All patients reported to be satisfied with the results at the end of the treatment;
5. Sensitivity appeared not to be an issue and none of the patients expressed concern or
complained about this side effect.
a
BriteSmileTM,Inc., Walnut Creek, CA 94598;(925) 941-6260
b
Ultradent Products Inc., South Jordan, UT USA
c
VITA Zahnfabrik, Bad Säckingen, Germany
d
Olympus Camedia C2500L-SLR, Olympus America Inc., Melville, NY USA
e
Dental Eye III, Yashica-kyocera, Somerset, New Jersey USA
Tables:
Vita Shade Guide c scores from the lightest to the darkest shade in
numeric code order.
Mean Shade Change from Baseline
Mean Shade Change from Baseline
Results showed from digital photography analysis
Table I:
Table II:
Table III:
Table IV:
TABLE I
Lightest
Darkest
B1
A1
B2
D2
A2
C1
C2
D4
A3
D3
B3
A3.5
B4
C3
A4
C4
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Corresponding Numeric Code
74
TABLE II
Patient
Teeth
1
central
lateral
canine
central
lateral
canine
central
2
3
lateral
canine
4
6
8
9
10
A3.5
A3.5
A2
A2
A3.5
central
lateral
canine
central
lateral
7
C1
A2
B3
B4
B4
A4
A3
central
lateral
canine
5
Initial
Shade
(# 6-11)
A2
A2
A3
D3
A3.5
canine
central
lateral
canine
central
lateral
canine
central
lateral
canine
central
lateral
canine
A4
A2
A2
B3
A2
A2
A3
D3
A3
A3.5
A2
A2
A3.5
A1 (4)
B1 (4)
A1 (9)
A2 (8)
A1 (11)
A3 (6)
B1 (8)
Opal. Xtra
Boost
(#9-11)
Postoper.
A1 (4)
A1 (3)
A3 (2)
A2 (8)
D2 (9)
A3 (6)
B2 (6)
A1 (4)
A1 (3)
A2 (6)
C2 (6)
C1 (7)
A3 (6)
A1 (7)
Opal. Xt.
Boost
(#9-11)
2 w. rec.
A1 (4)
A1 (3)
A2 (6)
C2 (6)
C1 (7)
A3 (6)
A1 (7)
B1 (11)
A2 (7)
A2 (7)
A2 (7)
A2 (7)
A3 (3)
A2 (7)
A2 (7)
A1 (3)
A1 (3)
A1 (3)
A1 (3)
A1 (3)
A1 (3)
A1 (3)
A1 (3)
A2 (7)
A2 (7)
A2 (7)
A2 (7)
B1 (4)
A1 (3)
A1 (7)
A1 (8)
B1 (4)
A1 (3)
D2 (5)
B2 (7)
D2 (1)
D2 (1)
D2 (5)
A1 (8)
D2 (1)
D2 (1)
D2 (5)
A1 (8)
A1 (10)
A2 (7)
A2 (7)
A2 (7)
A3 (6)
A1 (3)
A1 (3)
A2 (6)
A1 (3)
A1 (3)
B2 (6)
A1 (8)
D2 (5)
A2 (7)
A1 (3)
B1 (4)
A3.5 (3)
B2 (2)
A1 (3)
A3 (2)
A2 (0)
A2 (0)
A3 (0)
A2 (5)
A2 (4)
A3 (3)
A1 (3)
B1 (4)
A3 (6)
A1 (3)
A1 (3)
A2 (6)
A1 (3)
A1 (3)
A3 (0)
A2 (5)
A2 (4)
A3 (3)
A1 (3)
B1 (4)
A2 (10)
B2 (2)
A1 (3)
A3 (2)
B2 (2)
A1 (3)
A2 (4)
A2 (5)
A2 (4)
A3 (3)
A1 (3)
B1 (4)
A2 (7)
A3 (3)
A2 (7)
A2 (7)
Brite Smile
(# 6-8)
Postoper.
75
Brite Smile
(# 6-8)
2 w. recall
TABLE III
Mean Shade Change from Baseline
12
10
8
6
4
2
0
-2
Brite Smile - Brite Smile - 2 Opal Boost - Opal Boost - 2
After bleaching week recall After bleaching week recall
n
Mean
SD
SE
95% CI of Mean Median
IQR
95% CI of Median
Brite Smile After bleaching 30 5.900
2.524 0.461
4.958 to 6.842
6.000
4.000 4.000 to 7.000
Brite Smile 2 week recall
30 4.600
2.143 0.391
3.800 to 5.400
4.500
3.250 3.000 to 6.000
Opal Boost After bleaching 30 3.967
2.327 0.425
3.098 to 4.835
3.000
2.250 3.000 to 5.000
Opal Boost 2 week recall
2.294 0.419
3.810 to 5.523
4.000
4.000 3.000 to 6.000
30 4.667
TABLE IV
Pre
Post
2 Week
Brite Smile
Ultradent Boost Brite Smile
Ultradent Boost
L*
a*
b*
L*
a*
b*
L*
a*
b*
L*
a*
b*
L*
a*
b*
Mean
70.4 -2.8 7.3 73.6 -2.6 0.2 72.5 -1.9 3.2 74.0 -2.4 1.6 74.2 -1.9 2.0
St.Dev. 7.4 1.9 4.4 6.0 0.7 2.3 6.1 1.2 3.0 5.4 0.9 1.8 5.3 1.3 2.4
76
REFERENCES
1. Tavares M. Stultz J. Newman M. Smith V. Kent R. Carpino E. Goodson JM. Light augments
tooth whitening with peroxide.[comment]. Journal of the American Dental Association.
134(2):167-75, 2003 Feb
2. Hein DK. Ploeger BJ. Hartup JK. Wagstaff RS. Palmer TM. Hansen LD. In-office vital tooth
bleaching--what do lights add?. Compendium of Continuing Education in Dentistry. 24(4A):34052, 2003 Apr.
3. Papathanasiou A, Kastali S, Perry RD, Kugel G. Clinical evaluation of a 35% hydrogen
peroxide in-office whitening system. Compend Contin Educ Dent. 2002 Apr; 23(4): 335-8, 340,
343-4 passim; quiz 348
4. Jones AH, Diaz-Arnold AM, Vargas MA, Cobb DS.Colorimetric assessment of laser and
home bleaching techniques. J Esthet Dent. 1999; 11(2): 87-94
5. Anonymous. Laser-assisted bleaching: an update. ADA Council on Scientific
Affairs.[comment]. Journal of the American Dental Association. 129(10):1484-7, 1998 Oct
6. Goldstein RE. Esthetics in Dentistry-Principles, Comunications, Treatment Methods. 2nd ed;vol 1. Hamilton-London: B.C BeckerYear Book; 1998:245.
7. Cohen S, Parkins FM. Bleaching tetracycline-stained vital teeth. Oral Surg 1970 Mar; 29:46571
8. Goldstein RE, Garber DA. Complete dental bleaching. Chicago: Quintessence, 1995
9. Clinical Research Associates. Tooth Bleaching, state-of-art ’97. CRA Newsletter. April, 1997
10. Haywood VB, Heymann HO. Nightguard vital bleaching. Quintessence Int 1989;20:
173-6.
11. Jones AH. Diaz-Arnold AM. Vargas MA. Cobb DS. Colorimetric assessment of laser and
home bleaching techniques. Journal of Esthetic Dentistry. 11(2):87-94, 1999
12. Baik JW, Rueggeberg FA, LiewehrFR. Effect of light-enhanced bleaching on in vitro surface
and intrapulpal temperature rise. J Esthet Restor Dent. 2001; 13(6): 370-8
13. Haywood VB. Historical development of whiteners: clinical safety and efficacy. Dent
Update. 1997;24:98-104.
14. Gegauff AG, Rosenstiel SF, Langhout KJ, Johnston WM.Evaluating tooth color
change from carbamide peroxide gel. J Am Dent Assoc. 1993;124:65-72
15. Kugel G, Aboushala A, Sharma S, Ferreira S, Anderson C. Maintenance of
Whitening with Sonicare Advance Toothbrush after bleaching treatment. Compend
Contin Educ Dent. 2004 Feb; 25(2): 17-24; quiz 25
16. Anderson C, Kugel G. Rebound evaluation of tetracycline stained subjects treated
with a 6.5% hydrogen peroxide gel; quantitative assessment by standard digital
photography[abstract]. J Dent Res. 2002;81(special issue):A-429.Abstract 3488.
17. Deliperi S, Bardwell D, Papathanasiou A, Kim M-J. Effectiveness of a Combined In-office
and Take-home Bleaching System. AADR Abstract. March 2003
18. Papathanasiou A, Deliperi S, Bardwell D, Wegley C. In vitro Evaluation of a Combined
In-office and Take-home Bleaching System. AADR Abstract. March 2003.
77
Chapter 6
Tooth whitening and its Effect on Dentin
Daily Use of Whitening Strips on Tetracycline Stained Teeth:
Comparative Results After Two Months
ABSTRACT
This clinical article reviews the efficacy of a new 6.5% hydrogen peroxide tooth-whitening gel
strip for bleaching teeth that have been intrinsically stained from tetracycline. Given the severity
of the staining in the cases presented during a recently conducted clinical trial, the resulting
efficacy is dramatic. Additionally, the continuous use of these strips for 30 minutes per day,
twice daily for 4 months with no adverse effects—unlike many previously prescribed whitening
alternatives—is also noteworthy.
INTRODUCTION
In cases requiring esthetic enhancement of discolored dentition, those involving tetracycline
stains are among the most challenging. These intrinsic stains, which cannot be removed with
polishing or abrasive mechanisms, may result from the administration of tetracycline during
childhood for the treatment of disease. The color and severity of stains vary and are influenced
by the duration of tetracycline use, and the stage of tooth development at the time the
medication was prescribed. While some patients may select veneers or full-coverage crown
restorations as the method with which to brighten their smile, still others may desire a more
conservative approach. To that end, tooth whitening offers a conservative, simplified, and
economical alternative for changing tooth color.
78
When clinicians are faced with the prospect of whitening a patient’s intrinsically stained teeth,
considerations for treatment include shade and location of discoloration,1 as well as which
formulation of whitening solutions to use. Whether whitening should take place in the office or at
home under the dentist’s supervision, along with the longevity of the whitening protocol, must
also be decided. It has been suggested that when discoloration appears at the neck of the tooth,
the whitening results may be poorest; when the stain is dark gray or blue, the prognosis is
similarly unimpressive. When whitening tetracycline-stained teeth, patients may need to commit
to a course of treatment lasting several weeks or months.2-4
Treatment commonly involves the use of at-home vital bleaching kits, which were first
introduced in 1989.5 According to some reports, tetracycline-stained teeth have been shown to
demonstrate a favorable prognosis dependent upon the treatment considerations, even though
they are the most resistant to bleaching.6 Specifically, one report showed that 97% of patients
with tetracycline stains experienced successful tooth lightening when a carbamide peroxide
whitening solution was used in a nightguard.1
A recently introduced 6.5% hydrogen peroxide whitening delivery system (Crest® Professional
Whitestrips)a shows promise for use in whitening tetracycline-stained dentition when used at
home for two months and under a dentist’s supervision. The hydrogen peroxide-impregnated
polyethylene strips represent a treatment alternative for patients who cannot afford the cost of
other whitening treatments and/or do not have time for multiple dental visits.7 This article
presents the recent research findings of a clinical trial designed to evaluate the efficacy of two
at-home vital bleaching systems on tetracycline-stained teeth.
METHODS
A randomized clinical trial compared the efficacy of two at-home vital bleaching systems on
tetracycline-stained teeth. Daily bleaching was conducted over two months. Eligibility was
79
limited to healthy adult volunteers who had 16 or more natural teeth, including at least 3
gradable maxillary incisors with significant tetracycline staining. Individuals demonstrating tooth
sensitivity or an immediate need for dental treatment were excluded from participation in this
trial.
The study protocol, informed consent, and advertising were reviewed and approved by the
Institutional Review Board. Written and verbal informed consent was received prior to study
initiation. After informed consent and baseline measurements, subjects were randomized 3:1 to
a strip-based, hydrogen peroxide tooth-whitening system (Crest® Professional Whitestrips) or a
marketed tray-based, carbamide peroxide whitening system control (Opalescence® 10%)b.
Subjects in both groups were supplied with a standard dentifrice (Crest® Cavity Protection
Regular Paste)a, and soft toothbrush (Crest® Complete)a, for use throughout the study. All test
products were overpackaged in 1-month product kits, and all labeling was identical except for a
unique subject identification number.
The 40 randomized subjects included 30 assigned to the strip group and 10 assigned to
the tray group. The study population ranged from 22 to 70 years of age. Approximately
half of the sample presented with moderate to severe tetracycline staining (levels II
through IV), one third of who had the more severe banding that is occasionally reported
following childhood antibiotic use. While tobacco use was uncommon (15% of the
sample), 95% of the study participants consumed coffee, tea, or cola beverages daily.
Treatment groups were generally well balanced with respect to demographic and
behavioral parameters and tetracycline stain levels.
80
The first product application was supervised for instructional purposes, but all other treatment
was unsupervised. Only the maxillary arch was treated. Participants in the strip group were
instructed to wear a whitening strip for 30 minutes twice daily. Individuals in the tray group had a
custom soft, full-arch bleaching tray fabricated with gingival scalloping and gel reservoirs using
materials supplied by the manufacturer. Subjects in that group were instructed to place one half
to three quarters of the contents of a bleaching syringe into the custom tray and wear the device
for two hours daily.
Clinical response was evaluated at entry and again each month after treatment. First, the level
of tetracycline staining on the maxillary anterior teeth was assessed using a modified standard
3-point index.8 This modification recognized the possibility of successfully bleaching teeth with
relatively severe tetracycline stain (Table 1). These baseline values, along with age, were used
for balance and assignment during treatment randomization. Efficacy was assessed using a
standard 16-step value-oriented tooth shade guidec used in dentistry to match artificial crowns
to the natural dentition. Shade assessments were performed in a neutral-colored dental
operatory under color-balanced lighting conditions by a trained and calibrated examiner.
Tolerability was assessed by intraoral examination and subject report at each study visit (Table
1).
Individual shade scores were determined by ordering the 16 shades arranged from dark to light
according to the rank ordering suggested by the manufacturer. To account for unusually dark
colors (often seen with tetracycline stain) or white colors (often seen postbleaching), this 16step guide was supplemented by 2 additional values (C4+ and B1-) representing shades darker
than C4 or lighter than B1. Effectiveness was determined by calculating the change in shade
scores from baseline at each posttreatment visit. Using this method, a decrease in numeric
shade score represented an increase in tooth whiteness. Treatment groups were compared
81
using analysis of covariance with the baseline shade as the covariant. Comparisons to baseline
were 1-sided, while between-group comparisons were 2-sided using a 5% significance level.
RESULTS
Both treatments were effective overall in improving the shade of tetracycline-stained teeth
(Table 2). Relative to baseline, the 2 groups averaged approximately 4 to 6.5 units of shade
improvement after 2 months of treatment. Observed changes were greater on average after 2
months as compared to 1 month. Response was faster in the strip group. During the first
month’s treatment, individuals in the strip group averaged greater than a 4-unit reduction in
tooth shade, which represented a highly statistically significant (P < .0001) improvement vs
baseline. In contrast, subjects in the tray group averaged less than a 1-shade reduction during
the first month, not differing statistically from baseline (P > .10). Adjusting for baseline, the strip
group averaged 2.6 to 3.2 units more shade reduction compared with the tray group control.
With respect to between-group comparisons, the strip group experienced statistically
significantly superior reductions (P < .01) in shade compared with the tray group at both the 1and 2-month time points (Table 3).
Both treatments were generally well tolerated. Mild and transient tooth sensitivity and oral
irritation were the most common adverse events associated with daily bleaching (Table 4). All
such events were typically reported early in the treatment regimen, and there were no clinical
manifestations present at the Month 1 or Month 2 clinical examinations. Six subjects
discontinued treatment during the first 2 months (3 in each treatment group). Of these, 2
individuals in the tray group reported the regimen was inconvenient and withdrew after the
Month 1 visit. No one withdrew early or reported modifying their treatment regimen because of
an adverse event.
82
DISCUSSION
This study was designed to evaluate clinical response following longer-term, daily use of 6.5%
hydrogen peroxide whitening strips. The researchers elected to test extended treatment in
individuals with tetracycline staining, because this clinical condition is reported to require
extended treatment of several weeks or months in order to achieve meaningful whitening.9 A
marketed 10% carbamide peroxide, tray-based system was selected as the control group,
because this agent has been previously used and reported to be effective in longer-term studies
of tetracycline staining.10,11
Both the strip and tray-bleaching systems were effective, with both groups differing significantly
from baseline at the end of the 2-month monitoring period. Color response in the strip group
was superior to the tray group, as evidenced by the significant (P < .01) between-group
treatment differences at both Months 1 and 2, favoring the “trayless” whitening strip system.
Onset of these clinical benefits was more rapid in the strip group. After 1 month of treatment, the
strip group averaged more than a 4-shade improvement compared to less than 1 shade in the
tray group, with only the strip group experiencing statistically significant improvements in tooth
color after 1 month. After 2 months, the strip group averaged a 67% greater shade improvement
overall compared to the tray control group. While overnight tray use may improve clinical
response in that group, such daily treatment conducted during the long term could also affect
subject compliance.
Treatment response in some individuals was impressive (Figures 1 and 2). However, this study
confirms early observations of the need for extended contact time in many tetracycline-stained
patients. After 2 months of daily treatment, involving approximately 60 hours of strip use or 120
hours of tray use, no subjects had yet reached the predetermined bleaching cutoff (B1-). In
these subjects, additional time may be necessary to affect maximum color change. Previous
reports suggest a minimum of 2 months of treatment, hence the time point elected in this
83
study.12 The researchers expect to continue treatment and observation of this study population
for up to 6 months to further assess the effectiveness and tolerability of these agents with even
longer-term exposure.
Twice-daily use of the 6.5% hydrogen peroxide whitening strips was well tolerated over the 2month treatment period. The side effects in this study—transient tooth sensitivity and gingival
irritation—were generally similar in nature and severity to the primary events reported in other
longitudinal trials using the at-home tray-bleaching systems.9 In the current study, where the
whitening strips were used for a total of 60 contact hours over a 2-month period, no subject in
the strip group discontinued treatment due to an adverse event. This extended exposure
associated with long-term, daily treatment of tetracycline stain corroborates and extends the
safety of strip-based tooth whitening as reported in earlier, shorter-duration clinical trials.13-20
CONCLUSION
The use of whitening strips has been proposed as a viable option for longer-term whitening
because of favorable compliance, lower systemic exposure, and other factors associated with
this easy-to-use bleaching system.14 New clinical research involving extended treatment of
tetracycline stain over 2 months confirms this proposition. In the current study, daily treatment
for 1 month with a 6.5% hydrogen peroxide whitening strip provided similar efficacy as 2 months
of treatment with a 10% carbamide peroxide tray system.
84
Tables
Table 1—Tetracycline Stain Classification
Table 2—Baseline Demographic and Behavioral Information
Table 3—Tooth Shade by Treatment and Time
Table 4—Tooth Sensitivity and Oral Irritation
Table 1—Tetracycline Stain Classification*
Score
Clinical Presentation
0
No tetracycline staining evident
I
Uniform light yellow, brown, or grey stain confined to incisal three-quarters of
the crown
II
Deep yellow, brown, or grey stain, without banding
III
Dark grey or blue stain with marked banding
IV
More severe or extreme staining
*Modified from Boksman and Jordan, 1983.
85
Table 2—Baseline Demographic, Behavioral and Tooth Shade Information
Demographic
Strip
Characteristic/Statistic
Tray
Overall
Two-Sided
(n =30)
(n =10)
(n =40)
.7591
P-value
Age (Years)
Mean (SD)
37.7 (9.46)
38.9 (14.72)
38 (10.81)
Minimum - Maximum
22 - 58
25 - 70
22 - 70
Female
19 (63.3%)
3 (30%)
22 (55%)
Male
11 (36.7%)
7 (70%)
18 (45%)
Asian (Oriental)
6 (20%)
4 (40%)
10 (25%)
Caucasian
24 (80%)
6 (60%)
30 (75%)
No
25 (83.3%)
9 (90%)
34 (85%)
Yes
5 (16.7%)
1 (10%)
6 (15%)
Sex
.1401
Race
.2323
Tobacco Use
1.0000
Daily Coffee/Tea/Cola Consumption
No
2 (6.7%)
0 (0.0%)
2 (5%)
Yes
28 (93.3%)
10 (100%)
38 (95%)
1.0000
Tetracycline Stain Levels
I
15 (50%)
4 (40%)
19 (47.5%)
II
7 (23.3%)
1 (10%)
8 (20%)
III
8 (26.7%)
4 (40%)
12 (30%)
IV
0 (0.0%)
1 (10%)
1 (2.5%)
Mean
11.1
13.5
11.7
Minimum-Maximum
6-17
7-17
6-17
.3176
Tooth Shade
86
.0823
Table 3—Tooth Shade by Treatmemt and Time
Comparison to Baseline
Between-Group
Comparisons
N
Mean Change
(S.E.)
P-Value
Mean P-Value
Treatment
Difference
(S.E.)
Month 1
Strip
26
-4.05 (0.397)
<. 0001
Tray
9
-0.9 (0.696)
0.1014
Strip
26
-6.6 (0.418)
<. 0001
Tray
7
-3.96 (0.835)
<. 0001
-3.15 (0.852)
.0005
-2.63 (0.993)
.0097
Month 2
Table 4—Tooth Sensitivity and Oral Irritation
Strip Tray Overall
(n=30)(n=10)(n=40)
No.
%
No.
%
No.
%
Subj.
Subj.
Subj.
Subj.
Subj.
Subj.
Gingival Irritation
10
33.3
1
10
11
27.5
Tooth Sensitivity
13
43.3
4
40
17
42.5
0
0
0
0
0
0
Reported
Observed
Gingival Irritation
87
PRODUCT REFERENCES
a
The Procter & Gamble Co, Cinncinati, OH 45202; 800-492-7378
b
Ultradent Products, Inc, South Jordan, UT 84095; 800-552-5512
c
Vita Zahnfabrik, Germany; distributed in the US by Vident™, Brea, CA 92621; 800-828-3839
REFERENCES
1. Haywood VB, Leonard RH, Nelson CF, et al: Effectiveness, side effects and long-term status
of nightguard vital bleaching. J Am Dent Assoc 125(9):1219-1226, 1994.
2. Haywood VB, Leonard RH, Dickinson GL: Efficacy of six months of nightguard vital
bleaching of tetracycline-stained teeth. J Esthet Dent 9(1):13-19, 1997.
3. Haywood VB: Extended bleaching of tetracycline-stained teeth. Contemporary Esthetics and
Restorative Practice 1(1):14-21, 1997.
4. Haywood VB: Bleaching tetracycline-stained teeth. Esthet Dent Update 7(1):25-26, 1996.
5. Haywood VB, Heymann HO: Nightguard vital bleaching. Quintessence Int 20(3):173-176,
1989.
6. Haywood VB, Leonard RH, Nelson CF: Efficacy of 6-months nightguard vital bleaching of
tetracycline-stained teeth. J Dent Res 73 1994.
7. Kugel G: Nontray whitening. Compend Contin Educ Dent 21(6):524-528, 2000.
8. Boksman L, Jordan RE: Conservative treatment of the stained dentition: vital bleaching. Aust
Dent J 28(2):67-72, 1983.
9. Leonard RH: Nightguard vital bleaching: Dark stains and long-term results. Compend Contin
Educ Dent 21(suppl 28):S18-S27, 2000.
10. Leonard RH, Haywood VB, Eagle JC, et al: Nightguard vital bleaching of tetracyclinestained teeth: 54 months post treatment. J Esthet Dent 11(5):265-77, 1999.
11. Matis BA, Wang Y, Jiang T, et al: Six-month evaluation of bleaching agents in patients with
tetracycline staining (abs). J Dent Res 80:182, 2001.
12. Haywood VB: Current status of nightguard vital bleaching. Compend Contin Educ Dent
21(suppl 28):S10-S17, 2000.
13. Gerlach RW: Shifting paradigms in whitening: introduction of a novel system for vital tooth
bleaching. Compend Contin Educ Dent 21(suppl 29):S4-S9, 2000.
14. Kugel G, Kastali S: Tooth whitening efficacy and safety: a randomized and controlled
clinical trial. Compend Contin Educ Dent 21(suppl 29):S16-S21, 2000.
15. Gerlach RW, Jeffers MJ, Pernik PS, et al: Impact of prior tooth brushing on whitening strip
clinical response (abs). J Dent Res 80:151, 2001.
16. Gerlach RW, Campolongo KL, Hoke PD, et al: Use of peroxide-containing polyethylene
strips: effect of dosing duration on initial and sustained shade change (abs). J Dent Res 80:150,
2001.
17. Gerlach RW, Gibb RD, Sagel PA: A randomized clinical trial comparing a novel 5.3%
hydrogen peroxide whitening strip to 10%, 15% and 20% carbamide peroxide tray-based
bleaching systems. Compend Contin Educ Dent 21(suppl 29):S22-S28, 2000.
18. McMillan DA, Gibb RD, Gerlach RW: Impact of increasing hydrogen peroxide concentration
on bleaching strip efficacy and tolerability (abs). J Dent Res 80:173, 2001.
19. Swift EJ, Heymann HO, Ritter AV, et al: Clinical evaluation of a novel “trayless”
tooth whitening system. J Dent Res 80:151, 2001
88
Chapter 7
Long Term Hydrogen Peroxide Exposure and its Effect on Dentin
Comparative Study of 6.5% Hydrogen Peroxide Bleaching Strips On Tetracycline
Stain: Clinical Response After Six Months Daily Use
ABSTRACT
BACKGROUND A variety of indications exist for bleaching single or multiple teeth, including
tetracycline staining. The primary objective of this study was to evaluate clinical response
following extended daily use of a trayless 6.5% hydrogen peroxide tooth bleaching gel (Crest®
Professional Whitestrips, The Proctor & Gamble, Cincinnati, OH USA) on tetracycline stain. In
this research, 10% carbamide peroxide in an at-home daytime tray delivery system
(Opalescence® 10%, Ultradent Products, Inc., South Jordan, UT, USA) was used for
comparison purposesas an experimental control.
MATERIALS AND METHODS In this single-blind clinical trial,
subjects were randomly
assigned to a Strip group (30 subjects) or a Tray group (10 subjects) following screening for
tetracycline staining. Subjects used their respective products for approximately 6 months, with
clinical safety and efficacy measurements taken at the end of each month. The strip product
was used for 30 minutes, twice daily (maxillary arch only). The tray product was used for 2
hours daily (maxillary arch only). Treatment efficacy was determined by the tooth color change
from baseline using an expanded Vita Shade guide.
RESULTS The Strip group averaged greater shade reduction compared to the day wear Tray
group at the Months 1, 2, and 3 visits, respectively. After Month 3, there were no significant
between-group differences in shade. Of the subjects in the Strip group, 65 % reached B1 tooth
color by Month 6, while 43% of subjects in Tray group obtained this result after 6 months. Both
treatments were generally well tolerated. Mild and transient tooth sensitivity (40-47%) and oral
irritation (30-47%) were the most common adverse events associated with daily bleaching, yet
89
neither affected study participation. Conclusions: Both the 6.5% H2O2 experimental bleaching
strip (Crest Professional Whitestrips) and daywear marketed tray-based carbamide peroxide
system (Opalescence 10%) provided significant tooth whitening in subjects with tetracycline
stain. The Strip group obtained the results in a shorter pproximately half the time compared to
the day wear Tray group.
CLINICAL SIGNIFICANCE
When used daily for 6 months, a 6.5% H2O2 bleaching strip and the 10% carbamide peroxide
tray system can be effective in whitening tetracycline stain. Both the professional strip and tray
systems were well tolerated throughout the 6-month usage period. This extended use provides
additional evidence of clinical safety associated with use of these products for vital bleaching.
INTRODCUTION
Aging, chromatogenic food and drinks, excessive fluoride intake, medication (tetracycline) and
others can be the cause of intrinsic stains. Tetracycline stains, though, are considered to be the
most difficult types of intrinsic stains to manage clinically. The devastating effect on tooth
formation of as little as one gram of tetracycline was recognized in the late 1950s1 and
confirmed by a study of cystic fibrosis patients by Swachman et al 2. In 1970, Cohen and
Parkins published a method for bleaching the discolored dentin of young adults with cystic
fibrosis who had undergone tetracycline treatment 3.
Different variations of tetracycline and derivates produce different colors in the tooth. When the
teeth are exposed to the sunlight, they become darker, with a distinct gray/blue tinge. It is
suggested that the reason that the front incisor teeth darken while the molars remain yellow
longer is the different exposure to light 3. The discoloration of the permanent dentition depends
on the amount and duration of tetracycline use4. The portion of the tooth, color and severity of
the stains can be determined by the stage of the tooth development at the time of the drug
administration. Tetracycline is incorporated into dentin during tooth calcification intra and post
90
partum, probably through chelation with calcium forming tetracycline orthophosphate 5. It can
be deposited in fetal tooth buds when administered in the third trimester of pregnancy or by a
child during the development of the tooth (between ages 3 to 4 months and 7 to 8 years) 6, 7.
Colors may vary intensity of gray, blue, brown and yellow. The different banding can also be
attributed to the variations of the tetracycline derivates.
Clinicians are aware of the results from the use of tetracycline in pregnancy and young children.
Even though physicians and dentists should seek other sources of treatment, tetracycline is still
the drug of choice for treatment of Rocky Mountain spotted fever and it is also the most
prescribed medication for acne.
Tetracycline stained teeth may respond to bleaching treatments but in a different rate from the
other types of stains 8,9. Treatment is usually achieved by at-home vital bleaching kits, which
were first introduced in 1989 10. The most common regimen in the literature involves overnight
application of the bleaching tray for periods of several months8.
Even with this extended
treatment, clinical outcomes may be mixed.
Recently, a strip-based system was developed to deliver peroxide topically without
fabrication of a custom tray
11,12.
This trayless approach may be particularly relevant
where professionally-directed long term use is indicated, and where compliance with
trays may be problematic12. This new research was conducted to extend strip treatment
over a much longer duration than heretofore in order to evaluate clinical safety and
effectiveness of vital bleaching in patient’s longer treatment.
MATERIALS AND METHODS
Clinical research was conducted to evaluate clinical safety and effectiveness of a hydrogen
peroxide-based tooth whitening system under conditions of extended (long term) daily use. The
research was a randomized, examiner-blind, parallel group clinical trial comparing two peroxide
systems that differed with respect to delivery, and peroxide source. The experimental group
91
was 6.5% hydrogen peroxide whitening strips (Crest® Professional Whitestrips, The Procter &
Gamble Co., Cincinnati, OH USA).
The comparison group positive control was a 10%
carbamide peroxide gel (Opalescence® 10%, Ultradent Products, Inc., South Jordan, UT, USA)
delivered in a custom bleaching tray.
This system, which carries the American Dental
Association “Seal of Acceptance”13 for tooth whitening products, has been shown to be safe and
effective in numerous clinical trials14,15,16,17.
Bleaching was conducted each day over a 6 month period.
The target population was
individuals with tetracycline staining, because these case types are widely recognized to require
several months of treatment
18
. Eligibility was limited to healthy adult volunteers who had a
minimum of 16 natural teeth, including all 4 maxillary central and lateral incisors, and at least 3
gradable maxillary incisors having clinical evidence of tetracycline-related staining. Individuals
with untreated periodontal disease or dental caries, or dentinal hypersensitivity were excluded
from participation.
The study protocol, informed consent, and advertising were reviewed and approved by Tufts
University Institutional Review Board. Written and verbal informed consent was received
prior to initiating the study. Because the tray system had been used for an extended period,
and shown to be safe, this research was specifically designed to thoroughly evaluate the
clinical safety and effectiveness of the strip system under extended usage conditions.
Because of the difficulty in identifying patients who would participate in long term research,
and to assure an adequate sample size in the strip group, subjects were randomized 3:1 to
the whitening strips or tray control group.
A dental impression was taken of the maxillary arch of those subjects assigned to the tray
group to make custom bleaching trays. Subjects in that group received a custom, soft, fullarch bleaching tray fabricated with gingival scalloping and gel reservoirs using materials
92
supplied by the manufacturer (Ultradent Products, Inc. South Jordan, UT USA). Each strip
kit contained one carton of 56 upper strips in pouches. Each tray kit contained 24 unit-dose
syringes and 1 pocket tray case for the custom maxillary bleaching tray. In addition to the
test products (and custom tray where appropriate), all subjects were supplied with an
anticavity dentifrice (Crest® Cavity Protection, The Procter & Gamble Co., Cincinnati, OH
USA), and 2 soft toothbrushes (Crest® Complete, The Procter & Gamble Co., Cincinnati, OH
USA). All study-related products and materials were dispensed every four weeks in nonidentifiable kits with. For blinding purposes, kit labeling was identical, except for a unique
subject identification numbers.
Only the maxillary arch was treated. Strip use was 30 minutes twice daily. Subjects in the
tray group were instructed to place half to three quarters of the contents of a bleaching
syringe into the custom tray and wear the device for 2 hours daily. Because both groups
were assigned to a peroxide-containing product, and because only the maxillary arch was
treated, all subjects were offered a marketed, peroxide-based tooth whitening system for
“compassionate use” on the mandibular arch after study completion.
Clinical response was evaluated at baseline and again every 4 weeks after treatment. The
level of tetracycline stain on the maxillary anterior teeth was assessed using a modified
standard index (Jordan and Boksman Tetracycline Stain Classification) that recognized the
possibility of successfully bleaching teeth with relatively severe tetracycline stain
19,9
.
Tetracycline stain (I or II versus III or IV) and age were used for balancing during treatment
randomization.
Efficacy was assessed using a standard 16-steptab value-oriented tooth shade guide (Vita
Lumin, Vita Zahhnfabrik, Bad Sackingen, Germany). Shade examinations were performed
93
under color-balanced lighting conditions by a trained and calibrated examiner. Safety was
assessed at baseline and each subsequent visit. Subjects were interviewed at each visit to
ascertain the occurrence of any tooth hypersensitivity and/or oral irritation anytime during
treatment. All adverse events were collected irrespective of causality. For subjects with
findings, severity and duration were assessed, along with any interventions (rescue
medications, treatment alteration, and the like) in accordance with pharmaceutical research
standards.
Where banding was present, shade measurements were based on the predominant shade
scored ofn the tooth outside of the banded zone. All shades were collected by an examiner
who was blind to treatment assignment. Individual shade scores were determined by
ranking the 16 shade tabs, arranged from light to dark, according to the rank order
suggested by the manufacturer. This value-ordered ranking assigned “B1” as the first
(lowest) step, and “C4” as the last (highest) step of the 16 possible outcomes. To account
for exceedingly light or dark tooth colors, shade scores were expanded to include two
additional categories representing colors lighter or darker than those available using this
value-oriented system: shade “B1–“ (whiter than “B1”) with a numerical code “0”, and shade
“C4+” (darker than “C4”) with numerical code “17”.
Effectiveness was determined by calculating the change in shade scores from baseline at
each post-treatment visit. Using the expanded 18-tabstep rank order, a decrease in numeric
shade score represented an increase in tooth whiteness. Anticipating the effectiveness of
long term peroxide treatment, any subject who reached the lowest numerical shade (B1 or
lower) before end-of-treatment was withdrawn from active treatment by the investigator. For
those subjects who were withdrawn from treatment (< or = B1 before Month 6), the “last
observation carried forward” method was used to compute shade improvement at
94
subsequent visits. Tobit censored regression models were used to adjust for possible bias
attributable to effectiveness-related early withdrawals20,21.
Treatment groups were
compared using analysis of covariance with the baseline shade as the covariant.
Comparisons to baseline were 1-sided, while between-group comparisons were 2-sided
using a 5% significance level.
RESULTS
Age at baseline ranged from 22 years to 70 years, with mean (SD) age of 38 (10.8) years (Table
1). Females accounted for 55% of the population. 25% of subjects reported Southeast Asian
origin.
There was considerable variation in tetracycline staining, with 52% of subjects
presenting with moderate-to-severe tetracycline staining (levels II-IV). Only one subject in the
tray group exhibited the most severe staining/banding (level IV) at baseline. Shade scores
ranged from 6 (corresponding to the “C1” tab) to 17 (“C4+”). While tobacco use was uncommon
(15% of the sample), 95% of study participants consumed coffee, tea, or cola beverages daily.
Treatment groups were balanced (p > 0.14) with respect to demographics, behavioral
parameters and tetracycline stain levels.
Both treatments were effective overall in improving the shade of tetracycline-stained teeth, as
evidenced by the significant (p < 0.05) improvement in shade after 1-2 months depending on
treatment.
After 1-month treatment, the strip group averaged more than a 4-shade
improvement compared to a less than 1 shade in the tray group. The strip group exhibited a
statistically significant (p<0.0001) improvement in tooth shade after 1 month (Table 2). Both
groups experienced incremental shade improvement with continued use after Month 1. This
incremental benefit was more apparent in the tray group, such that, by Month 4, there were no
significant (p > 0.48) differences between groups with respect to mean shade improvement from
baseline. After 6-months daily use, the groups averaged a 10-11 shade improvement from
baseline.
95
During the first 2 months of continuous daily treatment, no subjects in either treatment group
reached or exceeded the minimum shade level. By Month 3, only 2 subjects (both in the strip
group reached) reached “B1” or lighter and were withdrawn from treatment. After 6 months
daily treatment, 40% of study subjects still had not reached or exceeded this minimal shade cutoff. Use of Tobit (censored regression) models, which adjusted for the biases in the treatment
difference at Month 3, 4, 5 and 6 visits, yielded treatment differences ranging from 1.3 to 0.6
shades favoring of the strip group (Table 3). Groups differed significantly (p = 0.04) with respect
to this “carry-forward” response only at the Month 3 time point.
Mild and transient tooth sensitivity and oral irritation were the most common adverse events
associated with treatment (Table 4). Findings were symptomatic in nature, as there were no
product-related clinical manifestations present at any of the monthly clinical examinations.
Occurrence of tooth sensitivity and oral irritation, which ranged from 30-47%, was somewhat
higher in the strip group compared to the tray group. Onset was generally during the first month
of treatment, and transitory, resolving fully concurrent with treatment.
Six subjects discontinued treatment during the first 2 months (3 in each treatment group). Two
individuals (both in the tray group) found the daily treatment regimen to be inconvenient and
withdrew after the Month 1 visit. The other 4 were “lost-to-follow-up”. There were no systemic
or non-oral adverse events (nausea or others) relating to product usage anytime during the 6month treatment period.
No subjects reported using any “rescue medication” such as
analgesics because of treatment-related sensitivity. There were no reports of early withdrawal
due to a product-related adverse event, and none of the study subjects reported modifying
usage because of treatment-related irritation or sensitivity.
96
DISCUSSION
This study evaluated clinical response following longer-term, daily use of hydrogen peroxidecontaining whitening strips relative to thea carbamide peroxide day wear tray-based
group.control. The target population consisted of individuals with tetracycline staining, because
clinical research repeatedly has demonstrated the need for extended treatment over several
months to achieve meaningful whitening with these cases
220
. A marketed 10% carbamide
peroxide, tray-based system was selected for as the comparisoncontrol group, because this
agent has been previously reported to be safe and effective on tetracycline stain when used
overnight over a 6 month period.(1144) .. Subjects used their assigned treatment regimen
throughout the 6-month test period unless they reached an average Vita Shade score of “B1” or
lighter prior to last evaluation. Those attaining this degree of whiteness were withdrawn from
additional bleaching but were followed through the remainder of the trial for efficacy and safety
outcomes.
In this research, both the strip and tray bleaching systems were effective, yielding a highly
significant (p < 0.001) and similar 10-11 mean shade improvement from baseline after 6 months
use. That both systems were comparable with respect to end-of-treatment efficacy may be
expected given certain overt similarities between treatments. The 6.5% hydrogen peroxide strip
system was used twice daily for 30 minutes, a 1-hour total daily contact time.
The 10%
carbamide peroxide tray system (equivalent to ~3.5% hydrogen peroxide) was used once daily
for 2-hours.
In this study, onset of shade improvement was earlier, and the magnitude of the change was
greater with strips compared to trays. Through Month 3, the strip group exhibited a statistically
significant (p < 0.05) 1.3 to 3.2 shade improvement relative to the tray control.
What
accounteds for the significant between-group differences in shade improvement seen early in
treatment?
One likely explanation is that tTwice a day use of a strip for 30 minutes applied a
97
higher concentration of peroxide more frequently , which allows for episodic treatment, could
represent an easier regimen for some individuals when compared to 2-hours of continuous tray
use of the lower concentration carbamide peroxide gel. Other factors could have contributed to
these findings, including the small sample size in the tray group, differences in the tetracycline
staining at baseline, and/or compliance (strips versus the day wear regimen used for the trays).
The portability and flexibility of strips may aid in treatment compliance, especially early in the
treatment regimen. However, shade guides represent an imperfect measure of efficacy,
especially for complex clinical presentations like those seen with tetracycline staining. As such,
the comparative effectiveness of outcomes must be evaluated with caution because causality
cannot be assessed from multi-factorial research like this clinical trial.
This study provides new evidence of an expanded safety in-use with strip-based tooth
whitening. Both bleaching systems in this trial were well tolerated with daily use over a 6-month
treatment period. No subjects in either group discontinued treatment early due to productrelated adverse events. For the tray system, these findings corroborate other reports of safe
continuous daytime use of 10% carbamide peroxide on tetracycline stain
231,242
. The research
provides additional assurance of the clinical safety of this 10% carbamide peroxide tray system
with conventional use over a few weeks, and longer term use for treatment of tetracycline
staining. For the strip system, the findings provide first evidence of in-use clinical safety with
extended treatment. The research, which expands on an earlier report establishing clinical
safety at concentrations up to 6.5% hydrogen peroxide on strips for periods of up to 2 months
daily use, extends treatment duration through 6-months 9. Twice-daily use of the 6.5% hydrogen
peroxide whitening strips was well tolerated over that period, with the principal side effects being
—ttransient tooth sensitivity and gingival irritation. These events were observed to occur more
frequently in the strip group.
Differences in occurrence rates between groups could be
attributable to the higher peroxide concentration in the strip versus the day wear tray group, or
other factors, including random chance. —being similar in nature and severity to the carbamide
98
peroxide, tray-based control group. Compared to the earlier 2-month findings, extended use
resulted in only a few additional reports of sensitivity/irritation, with no increasing severity or
persistence. Longer-term use through Month 6 showed no evidence of any cumulative toxicity.
While the sample size is small, (n=7) this research also suggests that a 10% carbamide
peroxide tray based system can result a meaningful reduction in tetracycline stain with day-time
use. Previous research showed the effectiveness of 10% carbamide peroxide used overnight in
a tray based system 8. This new research suggests day-time use may be a viable option where
indicated due to compliance, patient preference or other factors.
Long term clinical trials of this duration may be particularly relevant in establishing clinical safety
associated with routine treatment, as a research model that evaluates extreme (intentional or
unintentional) use. Such research may only be appropriate with populations such as this one,
where long-term treatment is common and/or necessary to achieve a desired endpoint, where
ethical and experimental controls are adequate to interpret outcomes, and where rigorous and
sufficient exit criteria are established to assure in-use safety. Under these conditions, longer
duration trials represent a “torture test” of sorts, offering additional insight on short-term clinical
safety.
This extended duration research, wherein whitening strips were professionally-
dispensed following clinical examination, and used for 180 contact hours over a 6-month period
to treat tetracycline stain, corroborates and extends the safety of strip-based tooth whitening as
reported in earlier, shorter duration clinical trials 9,253-27,24.
Tetracycline staining is complex, and may necessitate extensive esthetic intervention. Vital
bleaching with professional tray or strip systems can yield an evident improvement in
appearance within a few weeks. While this non-invasive, treatment may need to continue over
an extended period.
Some individuals will show favorable response after 3-4 months, after
which treatment may be discontinued. Duration may be difficult to predict, given the variable
99
clinical manifestations of tetracycline staining. Practitioners and patients should be advised that
optimal bleaching of tetracycline staining may necessitate extended daily at-home treatment
over a period of 3-6 months. The costs, risks, and benefits of the various treatment options
must be considered as part of overall patient management.
CONCLUSION
Both the 6.5% hydrogen peroxide bleaching strip (Crest Professional Whitestrips) and the
daytime tray-based carbamide peroxide tray systems (Opalescence 10%) provided significant
tooth whitening of tetracycline stain. While shade improvement generally occurred earlier with
the strips compared to the trays, by Month 4, groups did not differ significantly in this whitening
end point. Both groups demonstrated similar results after 6 months. Daily use of strips or
daytime tray bleaching for an extended 6-month period (approximately 180 contact hours) was
generally well-tolerated, with no subjects discontinuing treatment early due to an adverse event,
and with the principal adverse events—mild tooth sensitivity or and oral irritation—being similar
to that seen with the at-home carbamide peroxide tray system.
100
Tables and Figures
Table 1.
BASELINE
DEMOGRAPHIC
CHARACTERISTICS
Table 2.
Treatment Comparisons, Mean Shade Change at Months 1-3
Figure 1.
Mean Shade Change by Group
Figure 2.
Percent of Subjects Who Reached Minimum (“B1”) Shade by Group
Table 3.
Treatment Comparisons, Percent of Subjects Who Reached Minimum Shade at
AND
TETRACYCLINE
STAINING
Months 3-6
Table 4.
Occurrence of Oral Irritation and Tooth Sensitivity
TABLE 1
BASELINE DEMOGRAPHIC CHARACTERISTICS AND TETRACYCLINE STAINING
CHARACTERISTIC
STATISTIC
STRIP GROUP
(n =30)
TRAY GROUP
(n =10)
OVERALL
(n =40)
TWO-SIDED
p-VALUE
37.7 (9.46)
38.9 (14.72)
38.0 (10.81)
0.7591
22 - 58
25 - 70
22 - 70
19 (63.3%)
11 (36.7%)
3 (30%)
7 (70%)
22 (55%)
18 (45%)
0.1401 e
15 (50%)
7 (23.3%)
8 (26.7%)
0 (0.0%)
4 (40%)
1 (10%)
4 (40%)
1 (10%)
19 (47.5%)
8 (20%)
12 (30%)
1 (2.5%)
0.3176 e
AGE (YEARS)
Mean (SD)
Minimum Maximum
Sex
Female
Male
TETRACYLINE STAIN LEVEL
I
II
III
IV
101
Table 2
Treatment Comparisons
Shade Change from Baseline at Months 1-3
CHANGE FROM BASELINE
N
ADJ.
(S.E.)
MEAN
ADJUSTED
MEAN CHANGE
(P-VALUE )
95%
C. I.
ADJUSTED
MEAN
TREATMENT
DIFFERENCE
(S.E.)
Strip
Group
26
8.13(0.397)
-4.05
(<0.001)
(-4.83,3.27)
-3.15
(0.852)
<0.001
Tray
Group
9
11.28(0.696) -0.9 (0.101)
Strip
Group
26
5.49(0.417)
-6.61
(<0.001)
(-7.43,5.79)
-2.64
(0.991)
0.010
Tray
Group
7
8.13(0.833)
-3.98
(<0.001)
(-5.61,2.34)
Strip
Group
26
3.52 (0.267)
-8.59
(<0.001)
(-9.11,8.07)
-1.26
(0.634)
0.048
Tray
Group
7
4.77 (0.533)
-7.33
(<0.001)
(-8.38,6.29)
Strip
Group
24
2.37 (0.309)
-9.84
(<.0001)
(-10.45,9.24)
-0.41
(0.713)
0.5484
Tray
Group
7
2.78 (0.592)
-9.43
(<.0001)
(-10.59,8.27)
Strip
Group
23
2.04 (0.262)
-10.35
(<.0001)
(-10.86,9.83)
-0.31
(0.593)
0.5876
Tray
Group
7
2.35 (0.49)
-10.04
(<.0001)
(-11,-9.08)
Strip
Group
23
1.71
(0.285)
-10.67
(<.0001)
(-11.23,10.12)
-0.18
(0.645)
0.7764
Tray
Group
7
1.89
(0.532)
-10.5
(<.0001)
(-11.54,9.45)
PVALUE
Month 1
(-2.27,0.46)
Month 2
Month 3
Month 4
Month 5
Month 6
102
Table 3
Treatment Comparisons
Percent of Subjects Who Reached Minimum Shade at Months 3-6
Subjects who Reached B1/B1-
Treatment Difference
N
# (%) SUBJECTS
P-VALUE
ADJUSTED
MEAN
TREATMENT
DIFFERENCE
(S.E.)
P-VALUE
Strip Group
26
2 (7.7%)
1.00
-1.26 (0.61)
0.039
Tray Group
7
0 (0%)
Strip Group
24
11 (45.8%)
0.202
-0.63 (0.96)
0.511
Tray Group
7
1 (14.3%)
Strip Group
23
12 (52.2%)
0.103
-0.60 (0.85)
0.481
Tray Group
7
1 (14.3%)
Strip Group
23
15 (65.2%)
0.394
-0.55 (1.25)
0.657
Tray Group
7
3 (42.9)
Month 3
Month 4
Month 5
Month 6
103
Table 4
OCCURRENCE OF ORAL IRRITATION AND TOOTH SENSITIVITY
STRIP
(n =30)a
AE SOURCE/AE CLASSIFICATION
GROUP TRAY
(n =10)a
GROUP OVERALL
(n =40)a
No.
Subj.
%
Subj.
No.
Subj.
%
Subj.
No.
Subj.
%
Subj.
13
14
43.3
46.7
3
4
30
40
16
18
40.0
45.0
0
0
0
0
0
0
Reported
Oral Discomfort
Tooth Sensitivity
Observed
Oral Irritation
Figure 1
104
Figure 2
105
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1. Arens D. The role of bleaching in esthetics. Dent Clin North Am 1989; 33:319-36
2. Swachman H, Fekete E, Kulezychi L, Foley T. The effect of long-term antibiotic therapy in
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3. Cohen S, Parkins FM. Bleaching tetracycline-stained vital teeth. Oral Surg 1970; 29:465
4. Christensen GJ: Bleaching vital tetracycline stained teeth. Quintessence Int.1978 Jun: 9(6):
13-9
5. Mello HS. The mechanism of tetracycline staining in primary and permanent teeth. J Dent
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6. Moffitt JM, Cooley RO, Olsen NH, et al. Prediction of tetracycline-induced tooth
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7. Mull MM. The tetracycline and the teeth. Dent Abstr 1967; 12:346-350
8. Haywood VB, Leonard RH. Six-and 12-month color stability after 6 months bleaching
tetracycline teeth [abstract 2891]. J Dent Res 1996; 75(special issue): 379
9. Kugel G, Aboushala A, Zhou X, Gerlach RW. Daily use of strips on tetracycline-stained
teeth: comparative results after 2 months. Comp of Cont Edu in Dent. Jan 2002; 23 (1A): 2934
10. Haywood VB, Heymann HO:Nightguard vital bleaching . Quintessence Int 20(3):173176,1989.
Kugel G. Nontray whitening. Compend Contin Educ Dent 2000;6:524-528.
11. Gerlach RW. Whitening paradigms 1 year later: Introduction of a novel
professional tooth-bleaching system. Compend Contin Educ Dent 2002;23:4-8.
12. Siew C. American Dental Association. ADA Guidelines for the acceptance of
tooth-whitening products. Compend Contin Educ Dent. Supplem (28): S44-7, 2000
Jun.
13. Haywood VB, Leonard RH, Dickinson GL. Efficacy of six months of nightguard vital
bleaching of tetracycline-stained teeth. J Esthet Dent. 1997;9:13-9.
14. Matis BA, Cochran MA, Eckert G, Carlson TJ. The efficacy and safety of a 10%
carbamide peroxide bleaching gel. Quintessence Int. 1998;29:555-63.
15. Gerlach RW, Gibb RD, Sagel PA. A randomized clinical trial comparing a novel 5.3%
hydrogen peroxide bleaching strip to 10%, 15% and 20% carbamide peroxide tray-based
bleaching systems. Compend Contin Educ Dent 2000;21:S22-S28.
16. Matis BA. Tray whitening: What the evidence shows. Compend Contin Educ Dent
2003;24:354-362.
17. Haywood VB. Frequently asked questions about bleaching. Compend Contin Educ Dent
2003;24:324-338.
18. Boksman L, Jordan RE. Conservative treatment of the stained dentition: vital bleaching.
Aust Dent J 1983;28:67-72.
19. Tobin, J. Estimation of Relationships for Limited Dependent Variables. Econometrica,
1958;26, 24 -36.
20. Green, W.H. Econometric Analysis, 2nd Edition, New York: Cambridge University Press,
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21. Leonard RH. Long-term treatment results with nightguard vital bleaching. Compend
Contin Educ Dent. 2003;24:364-74.
22. Leonard RH Jr, Haywood VB, Caplan DJ, Tart ND. Nightguard vital bleaching of
tetracycline-stained teeth: 90 months post treatment. J Esthet Restor Dent. 2003;15:142-52
23. Matis BA, Wang Y, Jiang T, Eckert GJ. Extended at-home bleaching of tetracyclinestained teeth with different concentrations of carbamide peroxide. Quintessence Int.
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24. Gerlach RW. Zhou X. Comparative clinical efficacy of two professional bleaching
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1. Li Y, Lee SS, Cartwright SL, Wilson AC. Comparison of clinical efficacy and safety of
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107
Chapter 8
Paint on delivery systems
A Clinical Comparison of Two Paint on Whitening Systems
INTRODUCTION
The use of peroxide to whiten teeth dates back over 100 years. The advent of patient-applied
kits, bleaching has become both common and popular, and use of peroxide is now generally
recognized as a safe and effective method for tooth whitening1-3. There are a variety of
indications for bleaching single or multiple teeth, including staining from chromagenic foods or
other sources, dental fluorosis, tetracycline staining and devital discolored teeth4-7. Delivery is
via in-office, at-home regimens, such as polyethylene strips and paint-on, or combination
regimens with or without professional supervision8-9.
Easy availability of over the counter whitening products has made whitening of teeth more
popular amongst people of all ages. There are different types of over the counter products like
whitening dentifrices, tray based, whitening strips and the recently introduced brush
applications.
Over the counter bleaching kit requires the consumer to use either a prefabricated tray or
fabricate their own semi-molded tray then fill it with supplied bleaching agents. These types are
less than ideal because the trays are not custom fitted and the formulation is not sophisticated
as those dispensed by the dentist.10
Whitening toothpastes contain mild abrasives to remove surface stains. The peroxide content in
the toothpastes are very low ( 1% or less ), also the exposures of the toothpastes on the tooth is
minimal hence any whitening minimal.11
108
Whitening Strips is an alternative to rigid tray system for vital tooth whitening. The strip
technology uses same peroxide chemistry used in tray systems. The main drawback is that they
are limited to the anterior teeth and cannot be easily adapted to the malposed teeth.
The latest inclusion to OTC products is a Brush technique. This technique is non-tray based
paint on application. These products include a 19% sodium percarbonate film (5.3% hydrogen
peroxide) along with an 18% carbamide peroxide paint-on gel. The advantages to the paint- on
products is ease of use as well as the elimination of the need for a tray. These systems also
limit gingival exposure. There is little data on efficacy of these products.
Study Objectives
The objective of this trial was to compare the safety and whitening efficacy of an experimental
liquid strip (four weeks of use) to Colgate Simply White (three weeks of use).
Study Design
This was a randomized, controlled, double-blind, parallel, single-center study. Fifty (50)
generally healthy subjects who desired to have their teeth whitened were enrolled in the study.
Subjects who qualified for the study based on the results of their Baseline visit were randomly
assigned to one of two treatment groups. The first product use was supervised at the Product
Distribution visit. All product use followed the labeled use instructions. Digital imaging and oral
tissue examinations were conducted at Baseline, Week 2, Week 3, and Week 4. Subjects
assigned to Simply White discontinued product use after the Week 3 visit and returned one
week later for digital imaging and oral tissue examinations. Subjects assigned to the
experimental product continued product use for all four weeks of the study. During the entire
109
study period (treatment and post-treatment), subjects brushed with Crest Cavity Protection
dentifrice and an extra-soft toothbrush.
.
Selection of Study Population
Fifty (50) generally healthy adults with a Vita Shade score of B2 or darker who met all study
entrance criteria were enrolled. Subjects who withdrew from the study were not replaced.
INCLUSION CRITERIA
To be included in this study, each subject must have:
a. presented with a Vita Shade score of B2 or darker on Teeth 8 and 9;
b. provided written informed consent prior to their participation and be given a copy of the
signed consent form;
c. been at least 18 years of age at the time of enrollment;
d. agreed not to participate in any other oral/dental product clinical studies during the course of
this study;
e. agreed to return for the scheduled visits and follow the study procedures; and
f.
agreed to refrain from the use of any non-study dentifrices and tooth whitening products for
the study duration.
EXCLUSION CRITERIA
The subjects were excluded from this study if they:
110
a. had dental crowns or clinically meaningful malocclusion involving the maxillary or
mandibular anterior dentition (also confirmed by Investigator at Baseline visit);
b. reported having teeth previously bleached by a professional treatment, over-the-counter
bleaching kit, or clinical trial test product;
c. presented with any pre-existing oral or medical condition that the examiner or Investigator
determined may have placed the subject at increased health risk from study participation;
d. had any dental care planned during the duration of the study that may have:

impacted the general health of the subject,

impacted the ability of the subject to bleach teeth according to the protocol,

required a dental prophylaxis, or

involved the anterior dentition;
e. were undergoing current treatment for gingivitis, periodontitis, or caries;
f.
were currently using a chlorhexidine mouth rinse or Listerine mouth rinse;
g. had teeth with clinically meaningful intrinsic staining due to tetracycline, fluorosis or
hypocalcification;
h. had self-reported dentinal sensitivity, or
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i.
had teeth that could not be imaged.
CONTINUANCE CRITERIA
Subjects may have been discontinued from the study or been excluded from the efficacy
analysis if they:
a. used a chlorhexidine mouth rinse and/or Listerine mouth rinse;
b. received a dental prophylaxis; or
c. used any tooth whitening products other than assigned study products.
Removal of Subjects from the Study
Subjects were encouraged to complete the full course of the study; however subjects may have
withdrawn from the study at any time or for any reason. The reason for withdrawal was
documented on the appropriate case report form (CRF). The Investigator may have removed
subjects from the study for medical reasons and where, in his judgment, there was significant
lack of compliance at any time.
Study Procedures
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There were 5 study visits. A table detailing the procedures performed at each visit is provided in
Table 1.
SCHEDULE OF EVENTS
Study No. 2002147
Table 1
Schedule of Events
PreTreatment
Treatment
Visit 2
Procedures
Visit 1
Product
Visit 3
Visit 4
Visit 5
Baseline
Distribution
Week 2
Week 3
Week 4
Informed Consent
X
Inclusion/Exclusion Criteria
X
Demographics
X
Balance & Assignment
X
Supervised Product
X
Application
Product Distribution
X
Product Return
X
Oral Status Interview
X
X
X
X
Oral Hard & Soft Tissue
X
X
X
X
X
X
X
Examination
Continuance Criteria
X
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Study No. 2002147
Table 1
Schedule of Events
PreTreatment
Treatment
Visit 2
Procedures
Digital Imaging
Visit 1
Product
Visit 3
Visit 4
Visit 5
Baseline
Distribution
Week 2
Week 3
Week 4
X
X
X
X
X
X
X
Adverse Events
Subject Accountability
X
BASELINE VISIT
Written informed consent was obtained from each subject following review of the study design
and test regimen. Demographic information and inclusion/exclusion criteria were obtained and
documented on the appropriate CRF. Each subject was given an oral status interview prior to
receiving an oral soft tissue (OST) examination that included a self-reported tooth sensitivity
assessment. Digital images of the facial anterior dentition were collected.
PRODUCT DISTRIBUTION/BALANCE & ASSIGNMENT VISIT
The b* and L* digital imaging scores obtained at the Baseline visit, along with age, were arrayed
to balance and assign subjects to treatment groups. Test product (kit boxes plus Crest) was
distributed and written instructions were reviewed. Subjects completed their first product use
under supervision.
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WEEK 2 VISIT
Approximately 2 weeks after beginning test product use, subjects returned to the clinical site.
Continuance criteria were assessed. An oral status interview and an oral exam were
conducted. Self-reported, clinical OST and tooth sensitivity abnormal findings not present at
Baseline were documented on the AE CRF. Digital images of the facial anterior dentition were
collected.
WEEK 3 VISIT
Approximately 3 weeks after beginning test product use, subjects returned to the clinical site.
Continuance criteria were assessed. An oral status interview and an oral tissue exam were
conducted. Self-reported, clinical OST and tooth sensitivity abnormal findings not present at
Baseline were documented on the AE CRF. Digital images of the facial anterior dentition were
collected. Subjects assigned to Simply White discontinued product use at this time (per
labeling), but continued to brush with the provided toothbrush and dentifrice.
WEEK 4 VISIT
Continuance criteria were assessed. An oral status interview and an OST exam were
conducted. Self-reported, clinical OST, and tooth sensitivity abnormal findings not present at
Baseline were documented on the AE CRF. Digital images of the facial anterior dentition were
collected. All test product was returned. Subjects were exited from the study
EFFICACY ASSESSMENTS
DIGITAL IMAGING CAMERA
The photographic system consisted of a HC2500 CCD high resolution digital camera
manufactured by Fuji. It was equipped with a Fujinon A8x12BMD, 1:2.8/12-96mm zoom lens
and a linear polarizer to permit cross-polarized light. Two 150-watt lights located on each side
of a CCD camera provided the lighting. The unit was connected to a personal computer which
115
recorded and analyzed the images. Prior to daily use, the system was calibrated to assure
proper operation. Additionally, a color standard was centered and imaged every hour, then was
removed prior to imaging subjects. Maxillary anterior facial surfaces were measured for tooth
color using the digital image technology. One color value (L* a* b*) was generated from the
complete surface of the measured teeth.
For each examination period, lighting in the exam room was background or ambient. Each
subject was asked to brush with water and an extra-soft toothbrush to dislodge any debris that
may have interfered with photography. The subject sat on a stool in front of a chin rest used to
hold the head still. The subject placed his/her chin on the chin rest, then positioned two plastic
retractors into the mouth to retract his/her lips and cheeks.
It was also acceptable for the subject to position the retractors, then place their chin on the chin
rest. The subject was instructed to use the retractors to retract his/her lips and cheeks (toward
their ears) as far as possible. The incisal edges of the front teeth were placed together and
centered in the camera. The chin rest may have been adjusted to bring the teeth into the plane
of focus and ensured the image was centered. Prior to exposure, the subject was instructed to
draw air through their teeth and to position their tongue away from the teeth so that the tongue
was not visible. By proper positioning of the camera, frontal images of each subject were taken
at each visit.
SAFETY ASSESSMENTS
In this study, an AE was defined as any negative oral cavity health effect, either reported by the
subject or noted by the Investigator. Serious adverse events (SAEs), which occurred during the
course of the study and were reported to or observed by the study Investigator/examiner, were
documented on the appropriate CRF. All SAEs were to be followed until resolution or until
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discharge from follow-up was warranted based on consultation between the Sponsor and the
Investigator.
Serious AEs were defined as one or more of the following: a) death, b) life-threatening, c)
required in-patient hospitalization, and d) resulted in persistent or significant disability. When
the Investigator was notified of an SAE, the Investigator must have promptly (within 24 hours)
notified Procter & Gamble (P&G, the CRA or the Medical Monitor) of the SAE, regardless of
causality. Within 5 working days, a written report describing the circumstances of the event
must have been submitted to P&G.
ORAL SOFT TISSUE (OST) EXAMINATION
Assessment of the OST was conducted via a visual examination of the oral cavity and perioral
area utilizing a standard dental light, dental mirror, and gauze. The structures examined
included the gingiva (free and attached), hard and soft palate, oropharynx/uvula, buccal
mucosa, tongue, floor of the mouth, labial mucosa, mucobuccal/mucolabial folds, lips, and
perioral area. All abnormal OST findings noted after test product assignment which were not
documented at Baseline, or were present at Baseline but had worsened during test product
usage, were recorded as AEs on the AE CRF.
TREATMENTS
Method of Assigning Subjects to Treatment Groups
After the Baseline visit, digital images were processed and subjects were randomly assigned in
approximately equal numbers to one of the two treatment groups. The randomization balanced
for Baseline b* and L* scores, as well as age. Subjects who resided in the same household
were assigned to identical marketed products. A statistician that was not a member of the
project team carried out the assignment procedure.
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TREATMENTS ADMINISTERED
Experimental Whitening Product
Subjects were instructed to follow their customary brushing regimen for the study duration using
the Crest Cavity Protection dentifrice and toothbrush provided. Prior to using the test product,
subjects were instructed to brush and dry their teeth. Subjects applied the liquid strip to the
facial surfaces of the maxillary anterior teeth once daily just prior to bedtime. Subjects were
instructed not to eat, drink, or smoke for 90 minutes following treatment application. The test
product was removed each morning by thoroughly brushing the teeth. Subjects were supplied
with written instructions and shown pictures on how to apply the product. The first product use
was completed under supervision at the Product Distribution visit. All other uses were
unsupervised at-home.
Colgate Simply White
Subjects followed the manufacturer directions for product use, and followed their customary
brushing regimen for the study duration using Crest Cavity Protection dentifrice and the
toothbrush provided. Prior to using the test product, subjects were instructed to brush and dry
their teeth. Subjects applied the whitening product to the facial surfaces of the maxillary anterior
teeth twice per day. Subjects were instructed not to eat or drink for 30 minutes following
treatment application. Subjects were supplied with the marketed instructions for use and shown
pictures on how to apply the product. The first product use is completed under supervision at
the Product Distribution visit. All other uses are unsupervised at-home.
IDENTITY OF INVESTIGATIONAL PRODUCTS

Experimental tooth whitener (19.0% sodium percarbonate, equivalent to 5.3% hydrogen
peroxide), manufactured by The Procter & Gamble Company. Packaged in individual
sachets / stick packs.
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
Colgate Simply White (commercial product)
Experimental Whitening Product
Each kit contained a four-week supply of single unit doses (sachets), 20 micro brushes for
product application, one tube of toothpaste (Cavity Protection Crest, The Procter & Gamble Co.,
Cincinnati, OH, USA) one extra-soft toothbrush (Crest Complete, The Procter & Gamble Co.,
Cincinnati, OH, USA), and one instruction sheet. The sachets were labeled with study number,
product number, applicable caution and warning statements, usage directions and other
information as dictated by internal regulatory requirements and clinical standard operating
procedures (SOPs).
Colgate Simply White
Product was supplied in subject kit boxes. Each kit contained one 0.34 oz polypropylene bottle
with applicator, one tube of toothpaste (Cavity Protection Crest, The Procter & Gamble Co.,
Cincinnati, OH, USA) one extra-soft toothbrush (Crest Complete, The Procter & Gamble Co.,
Cincinnati, OH, USA), and one instruction sheet. The kits were labeled with study number,
product number, applicable caution and warning statements, labeled usage directions and other
information as required by internal regulatory and clinical SOPs.
Supplemental product was provided to the Investigator if additional product was needed, and
was dispensed only after consulting with the Sponsor for correct treatment group identification.
The shipping containers were labeled with the "ship to" clinical site address and a "content
statement" listing study number and subject numbers contained within.
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BLINDING
This was a double-blind study. Product use was conducted in an area where the examiner was
not present. Subjects were instructed not to discuss product appearance or physical qualities
with the examiner.
TREATMENT COMPLIANCE
Subjects received verbal and written instructions on dentifrice usage. Subjects used their
product for the first time on site under supervision as part of the instructions. Subjects were
queried regarding compliance at each visit.
STATISTICAL ANALYSIS PLANS
The primary assessment compared the treatment groups for yellowness reduction (b*) at the
end-of-treatment visit. The secondary assessment compared the treatment groups for
yellowness reduction (b*) at the Week 2 visit. The tertiary assessment compared the
treatment groups for yellowness reduction (b*) at the end-of-study visit. The mean whitening
benefit for each treatment group was assessed at the post-baseline visits. The safety profile of
each treatment group was characterized.
Operational Trial Hypotheses
Tooth color was assessed by the digital imaging measurements b* (yellow – blue), L*
(lightness), and a* (red – green). For a given post-baseline visit: b* = b*visit - b*baseline, L* =
L*visit - L*baseline, a* = a*visit - a*baseline, and E* = (L*2 + a*2 + b*2) ½. In the case of tooth
color, whitening benefit resulted primarily from negative b* (yellowness reduction).
Additionally, positive L* (increasing lightness) and negative a* (redness reduction) may have
been observed. Changes in b*, L*, and a* resulted in increased E* (overall color change).
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An additional color quantity was computed from the L*a*b* color values for each subject and
visit: W* = (b*visit2 + a*visit2 + (L*visit - 100)2) ½ which represented the distance to pure white for a
given visit. One may have defined W* = (b*visit2 + a*visit2 + (L*visit - 100)2) ½ – (b*baseline2 +
a*baseline2 + (L*baseline - 100)2) ½ as the distance to pure white at a given visit minus the distance to
pure white at Baseline. In the equations above, pure whiteness was achieved when b* = 0, a* =
0, and L* = 100.
Primary Hypotheses
The following hypothesis was tested at the end-of-treatment visit.
Null:
The mean level of b* in the experimental group is equal to the mean level of b*
in the Simply White group.
Alternative: The mean level of b* in the experimental is not equal to the mean level of b* in
the Simply White group.
Secondary Hypotheses
The following hypothesis was tested at the Week 2 visit.
Null:
The mean level of b* in the experimental group is equal to the mean level of b*
in the Simply White group.
Alternative: The mean level of b* in the experimental is not equal to the mean level of b* in
the Simply White group.
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Tertiary Hypotheses
The following hypothesis was tested at the end-of-study visit.
Null:
The mean level of b* in the experimental group is equal to the mean level of b*
in the Simply White group.
Alternative: The mean level of b* in the experimental is not equal to the mean level of b* in
the Simply White group.
The following hypothesis was tested for each treatment group and post-baseline visit.
Null:
The mean level of b* is equal to zero.
Alternative: The mean level of b* is not equal to zero.
The hypotheses above were investigated for other color parameters as well.
Efficacy Analysis Plans
Summary statistics (e.g., means, standard deviations, frequencies, etc.) of the demographic
characteristics, b*, L*, a*, W*, and E* were calculated for each treatment group and visit. The
treatment groups were compared using analysis of covariance (ANCOVA) methods. The
response was color change from Baseline and the covariate was the color at Baseline. Age
was used as a covariate. Treatment comparisons were tested at the 0.05 level of significance.
Whitening benefit at each post-baseline visit was investigated using the mean color change
from Baseline within each treatment group and then performing one-sample t-tests.
Comparisons to Baseline were tested using a two-sided 0.05 level of significance.
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Safety Analysis Plans
The safety data were summarized with respect to tooth sensitivity and oral irritation. Following
the end-of-study visit, all AEs, including OST-related AEs and dentinal hypersensitivity AEs
were summarized overall and by treatment group. The safety data were also summarized
through the Week 2 visit.
POWER AND SAMPLE SIZE CONSIDERATIONS
At least 23 subjects per treatment group completing the study ensured at least 80% power to
detect a difference of 0.7 b* units between the treatment groups with a common standard
deviation of 0.7, in two-sided testing at a 0.05 significance level. A target of up to 25 subjects
was recruited per group (total of up to 50).
CHANGES TO THE ANALYSIS PLANS
All planned analyses were performed. In addition, efficacy comparisons were made between
Week 2 for the Experimental Film group and Week 3 for the Colgate Simply White group. Also,
the treatment groups were compared at the Week 3 visit as well. Safety data was also
summarized through the Week 2 visit of the study.
RESULTS
DISPOSITION OF SUBJECTS
Fifty-one subjects were screened, however, Subject 3021 was dropped from the study at
Baseline due to investigator recommendation. Fifty subjects were randomized to treatment, and
47 subjects received product. Three subjects failed to present for product distribution visit:
Subject 3007 voluntarily withdrew from the study, Subjects 3013 and 3041 were lost to follow-
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up. Thirty-nine subjects completed the study. Eight subjects 3024, 3025, 3027, 3032, 3033,
3045, 3057, 3016 were lost to follow-up (Table 3).
DATA SETS ANALYZED
Demographic, digital imaging and adverse event data were all analyzed for this study. Three
subjects failed to present for the product distribution visit: Subject 3007 voluntarily withdrew
from the study, Subjects 3013 and 3041 were lost to follow-up. In the Colgate Simply White
group, one subject (3045) was lost follow-up starting at the Week 2 visit and six subjects (3024,
3025, 3027, 3032, 3033, and 3057) were lost to follow-up at the Week 4 visit, two subjects
(3002 and 3015) each missed one visit. In the Experimental Film group, one subject (3016) was
lost follow-up starting at the Week 2 visit, two subjects (3008 and 3022) each missed one visit
(Table 3).
DEMOGRAPHIC AND BASELINE CHARACTERISTICS
Subjects ranged in age from 21 to 70 years with an average of 35 years. Sixty-four percent of
the subjects were female. Twenty-eight subjects (59.6%) were Caucasian, 12 subjects (25.5%)
were Black, 3 subjects (6.4%) were Asian, 2 subjects (4.3%) were Asian and 2 subjects (4.3%)
were Multi-racial. Cigarette and cigar smokers accounted for 10.6% of the subjects. Coffee,
tea, and dark cola drinkers accounted for 89.4% of the subjects with a median of 2 drinks per
day. Treatment groups were relatively balanced in demographic characteristics and behavioral
parameters (Table 4-5).
Efficacy Results
PRIMARY EFFICACY
The end-of-treatment comparison compared the Experimental Film group at Week 4 relative to
the Colgate Simply White group at Week 3. At the end-of-treatment visit, the Experimental Film
group provided more than 7.9 times greater reduction in yellowness (b*) when compared to the
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Colgate Simply White group with estimated means and standard errors of –0.782 ± 0.137 and –
0.098 ± 0.131, respectively. The treatment comparison for b* was statistically significant (pvalue = 0.0009 from Table 16).
SECONDARY EFFICACY
At Week 2 visit, the Experimental Film group provided more than 3.0 times greater reduction in
yellowness (b*) when compared to the Colgate Simply White group with estimated means and
standard errors of –0.691 ± 0.124 and –0.230 ± 0.116, respectively. The treatment comparison
for b* was statistically significant (p-value = 0.0109 from Table 11).
TERTIARY EFFICACY
At the end-of-study visit (Week 4), the Experimental Film group provided more than 4.4 times
greater reduction in yellowness (b*) when compared to the Colgate Simply White group with
estimated means and standard errors of –0.788 ± 0.140 and –0.177 ± 0.152, respectively. The
treatment comparison for b* was statistically significant (p-value = 0.006 from Table 11).
For the whitening benefit measured by mean change in b* (yellowness) from Baseline, the
Experimental Film group was effective at each post-baseline visit (p-values  0.0003 from Table
6), while the Colgate Simply White group was only statistically significant at the Week 2 visit (pvalue = 0.0305 from Table 6).
ADDITIONAL EFFICACY
Summary statistics were calculated for b*, L*, a*, W* and E* (Tables 6-10). The treatment
groups were well balanced on b* (yellowness), L* (lightness), and a* (redness) at Baseline.
Figure 1 displays the adjusted means of b* for each treatment group at each visit. Figure 2
displays the adjusted means of L* for each treatment group at each visit.
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END-OF-TREATMENT
(Experimental Film at Week 4 versus Colgate Simply White at Week 3)
At the end-of-treatment visit, the Experimental Film group provided more than 7.3 times greater
improvement in lightness (L*) when compared to the Colgate Simply White group with
estimated means and standard errors of 1.061± 0.124 and 0.145 ± 0.118, respectively. The
treatment comparison for L* was statistically significant (p-value < 0.0001 from Table 16). The
Experimental Film group provided more than 39 times greater improvement in redness (a*)
when compared to the Colgate Simply White group with estimated means and standard errors
of –0.394 ± 0.073 and –0.010 ± 0.070, respectively. The treatment comparison for a* was
statistically significant (p-value = 0.0005 from Table 16). The Experimental Film group provided
more than 8 times greater improvement in composite whiteness (W*) when compared to the
Colgate Simply White group with estimated means and standard errors of –1.377 ± 0.149 and
–0.172 ± 0.142, respectively. The treatment comparison for W* was statistically significant (pvalue < 0.0001 from Table 16). The Experimental Film group provided more than 2.3 times
greater overall color change (E*) when compared to the Colgate Simply White group with
estimated means and standard errors of 1.526 ± 0.137 and 0.670 ± 0.131, respectively. The
treatment comparison for E* was statistically significant (p-value < 0.0001 from Table 16).
ADDITIONAL TREATMENT COMPARISONS
(Experimental Film at Week 2 versus Colgate Simply White at Week 3)
The Experimental Film group at Week 2 provided more than 6.3 times greater reduction in
yellowness (b*) when compared to the Colgate Simply White group at Week 3 with estimated
means and standard errors of –0.691 ± 0.122 and –0.108 ± 0.114, respectively. The treatment
comparison for b* was statistically significant (p-value = 0.0014 from Table 17). The
Experimental Film group at Week 2 provided more than 4.5 times greater improvement in
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lightness (L*) when compared to the Colgate Simply White group at Week 3 with estimated
means and standard errors of 0.690 ± 0.114 and 0.152 ± 0.106, respectively. The treatment
comparison for L* was statistically significant (p-value = 0.0015 from Table 17). The
Experimental Film group at Week 2 provided more than 29.9 times greater improvement in
redness (a*) when compared to the Colgate Simply White group at Week 3 with estimated
means and standard errors of –0.419 ± 0.067 and –0.014 ± 0.062, respectively. The treatment
comparison for a* was statistically significant (p-value < 0.0001 from Table 17). The
Experimental Film group provided more than 5.5 times greater improvement in composite
whiteness (W*) when compared to the Colgate Simply White group with estimated means and
standard errors of –1.028 ± 0.138 and –0.185 ± 0.129, respectively. The treatment comparison
for W* was statistically significant (p-value < 0.0001 from Table 17). The Experimental Film
group provided more than 1.7 times greater overall color change (E*) when compared to the
Colgate Simply White group with estimated means and standard errors of 1.183 ± 0.114 and
0.683 ± 0.106, respectively. The treatment comparison for E* was statistically significant (pvalue = 0.0032 from Table 17).
Week 2 Comparisons
At the Week 2 visit, only Experimental Film group was effective in whitening teeth as measured
by mean change in L* (lightness) from Baseline (p-value < 0.0001 from Table 7). The
Experimental Film group provided more than 13 times greater improvement in lightness (L*)
when compared to the Colgate Simply White group with estimated means and standard errors
of 0.693 ± 0.132 and 0.053 ± 0.123, respectively. The treatment comparison for L* was
statistically significant (p-value = 0.0012 from Table 12). Both treatments were effective in
whitening teeth as measured by mean change in a* (redness) from Baseline: the Experimental
Film group had a p-value < 0.0001 and the Colgate Simply White group had a p-value equal to
0.0163 (Table 8). The Experimental Film group provided more than 3.4 times greater
improvement in redness (a*) when compared to the Colgate Simply White group with
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estimated means and standard errors of –0.430 ± 0.062 and –0.124 ± 0.058, respectively. The
treatment comparison for a* was statistically significant (p-value = 0.0010 from Table 13).
Only the Experimental Film group was effective in whitening teeth as measured by mean
change in W* (composite whiteness) from Baseline with p-value < 0.0001 (Table 9). The
Experimental Film provided more than 5.3 times greater improvement in composite whiteness
(W*) when compared to the Colgate Simply White group with estimated means and standard
errors of –1.034 ± 0.148 and –0.193 ± 0.138, respectively. The treatment comparison for W*
was statistically significant (p-value = 0.0002 from Table 14). Both treatments were effective at
increasing overall color change (E*) with p-values < 0.0001 (Table 10). The Experimental Film
group provided more than 1.5 times greater overall color change (E*) when compared to the
Colgate Simply White group with estimated means and standard errors of 1.199 ± 0.120 and
0.773 ± 0.112, respectively. The treatment comparison for E* was statistically significant (pvalue = 0.0154 from Table 15).
Week 3 Comparisons
At the Week 3 visit, the Experimental Film group provided more than 6.3 times greater reduction
in yellowness (b*) when compared to the Colgate Simply White group with estimated means
and standard errors of –0.705 ± 0.129 and –0.111 ± 0.123, respectively. The treatment
comparison for b* was statistically significant (p-value = 0.0021 from Table 11). Only the
Experimental Film group was effective in whitening teeth as measured by mean change in L*
(lightness) from Baseline (p-value < 0.0001 from Table 7). The Experimental Film group
provided more than 7 times greater improvement in lightness (L*) when compared to the
Colgate Simply White group with estimated means and standard errors of 1.071± 0.137 and
0.149 ± 0.131, respectively. The treatment comparison for L* was statistically significant (pvalue < 0.0001 from Table 12). Only the Experimental Film group effective in whitening teeth
as measured by mean change in a* (redness) from Baseline (p-value = 0.0025 from Table 8).
The Experimental Film provided more than 15.7 times greater improvement in redness (a*)
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when compared to the Colgate Simply White group with estimated means and standard errors
of –0.268 ± 0.069 and –0.017 ± 0.066, respectively. The treatment comparison for a* was
statistically significant (p-value = 0.0126 from Table 13). Only the Experimental Film group was
effective in whitening teeth as measured by mean change in W* (composite whiteness) from
Baseline with p-value < 0.0001 (Table 9). The Experimental Film group provided more than 6.9
times greater improvement in composite whiteness (W*) when compared to the Colgate
Simply White group with estimated means and standard errors of –1.313 ± 0.159 and –0.188 ±
0.152, respectively. The treatment comparison for W* was statistically significant (p-value <
0.0001 from Table 14). Both treatments were effective at increasing overall color change (E*)
with p-values < 0.0001 (Table 10). The Experimental Film provided more than 1.9 times greater
overall color change (E*) when compared to the Colgate Simply White group with estimated
means and standard errors of 1.464 ± 0.136 and 0.692 ± 0.129, respectively. The treatment
comparison for E* was statistically significant (p-value = 0.0002 from Table 15).
End-of-Study (Week 4) Comparisons
At the Week 4 visit, only the Experimental Film group was effective in whitening teeth as
measured by mean change in L* (lightness) from Baseline (p-value < 0.0001 from Table 7).
The Experimental Film group provided more than 4 times greater improvement in lightness (L*)
when compared to the Colgate Simply White group with estimated means and standard errors
of 1.065± 0.135 and 0.263 ± 0.146, respectively. The treatment comparison for L* was
statistically significant (p-value = 0.0003 from Table 12). Only the Experimental Film group
effective in whitening teeth as measured by mean change in a* (redness) from Baseline (pvalue = 0.0003 from Table 8). The Experimental Film group provided more than 3.8 times
greater improvement in redness (a*) when compared to the Colgate Simply White group with
estimated means and standard errors of –0.397 ± 0.072 and –0.104 ± 0.078, respectively. The
treatment comparison for a* was statistically significant (p-value = 0.0099 from Table 13).
Both treatments were effective in whitening teeth as measured by mean change in W*
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(composite whiteness) from Baseline with p-values ≤ 0.0029 (Table 9). The Experimental Film
group provided more than 4.2 times greater improvement in composite whiteness (W*) when
compared to the Colgate Simply White group with estimated means and standard errors of
–1.385 ± 0.146 and –0.325 ± 0.158, respectively. The treatment comparison for W* was
statistically significant (p-value < 0.0001 from Table 14). Both treatments were effective at
increasing overall color change (E*) with p-values < 0.0001 (Table 10). The Experimental Film
group provided more than 1.9 times greater overall color change (E*) when compared to the
Colgate Simply White group with estimated means and standard errors of 1.534 ± 0.147 and
0.788 ± 0.160, respectively. The treatment comparison for E* was statistically significant (pvalue = 0.0020 from Table 15).
SAFETY RESULTS
For Adverse Events Through Week 4 (End-of-Study)
Only the Experimental Film group had reported or observed tooth sensitivity and oral irritation.
Eight subjects (36.4%) reported oral irritation and four subjects (18.2%) reported tooth
sensitivity. Two subjects (9.1%) had both tooth sensitivity and oral irritation (Table 18.1).
Overall, there were a total of 14 adverse events involving 11 different study subjects: Ten
subjects in the Experimental Film group and one subject in the Colgate Simply White group
(Table 19.1). By type, the most frequently reported AEs were gingivitis and hyperesthesia
which accounted for 50% and 36%, respectively, of all events (Table 18).
One hundred percent of all events were “mild” in severity. No subjects discontinued treatment
early “for cause” – that is – due to a treatment-related adverse events (Table 3).
130
For Adverse Events Beginning On or Before Week 2
Only the Experimental Film group had reported or observed tooth sensitivity and oral irritation.
Two subjects (9.1%) reported oral irritation and two subjects reported tooth sensitivity. No
subjects reported both tooth sensitivity and oral irritation (Table 18.2). Overall, there were a
total of 5 adverse events involving 5 different study subjects who were all in the Experimental
Film group. One hundred percent of all events were “mild” in severity (Table 19.2).
CONCLUSIONS

The Experimental Film provided significant whitening improvement from Baseline as
measured by all color parameters at all post-baseline visits.

In general, the Colgate Simply White did not differ statistically from Baseline with the
exception of b* at the Week 2 visit.

The Experimental Film provided significant whitening improvement relative to Colgate
Simply White for all comparisons of interest and all color parameters. Whitening benefit
for the Experimental Film group improved slightly after 2 weeks of treatment, in contrast,
whitening benefit for the Colgate Simply White relapsed by Week 3 and rebounded for
subjects completing the study at 1 week post-treatment (Week 4).

Both products were generally well tolerated overall.
131
Tables and Figures
TABLE 1
SUBJECT DISPOSITION
NUMBER OF SUBJECTS ENROLLED AT EACH VISITa,b
VISIT
COLGATE SIMPLY WHITE
EXPERIMENTAL FILM
OVERALL
Baseline
25
25
50
Week 2
25
22
47
Week 3
25
22
47
Week 4
25
22
47
a
See Appendices 2.1 for data listing and evaluability memo for details.
b
Randomization to treatment occurred after the Baseline visit and prior to product distribution.
c
Fifty-one subjects were screened, however, Subject 3021 was dropped from the study at Baseline
due to investigator recommendation. Fifty subjects were enrolled and randomized to treatment,
and 47 subjects received product.
132
TABLE 2
SUMMARY OF EVALUABLE SUBJECT POPULATIONa
EVALUABLE
VISIT/
TREATMENT GROUP
NO.
SUBJ.
NO.
SUBJ.
SUBJ.
Colgate Simply White
25
25
Experimental Film
22
Overall
NON-EVALUABLE
%
NO.
SUBJ.
SUBJ.b
100.0
0
0.0
22
100.0
0
0.0
47
47
100.0
0
0.0
Colgate Simply White
25
23
92.0
2
8.0
Experimental Film
22
20
90.9
2
9.1
Overall
47
43
91.5
4
8.5
Colgate Simply White
25
23
92.0
2
8.0
Experimental Film
22
21
95.5
1
4.5
Overall
47
44
93.6
3
6.4
Colgate Simply White
25
18
72.0
7
28.0
Experimental Film
22
21
95.5
1
4.5
Overall
47
39
83.0
8
17.0
b
%
BASELINE
WEEK 2
WEEK 3
WEEK 4
a
See Appendices 3.1 and 4.1 for the statistical analysis program and output, respectively.
b
Percent of subjects evaluable or non-evaluable out of the number of subjects treated.
133
TABLE 3
LISTING OF SUBJECTS EXCLUDED FROM EVALUABLE POPULATIONa,b
TREATMENT/
SUBJECT NO.
COLGATE SIMPLY WHITE
3002
3015
3024
3025
3027
3032
3033
3045
3057
EXPERIMENTAL FILM
3008
3016
3022
NON-EVALUABLE
VISIT(S)c
REASON(S)
Week 3
Week 2
Week 4
Week 4
Week 4
Week 4
Week 4
Week 2+
Week 4
Missed Visit
Missed Visit
Lost to Follow-up
Lost to Follow-up
Lost to Follow-up
Lost to Follow-up
Lost to Follow-up
Lost to Follow-up
Lost to Follow-up
Week 3
Week 2+
Week 2
Missed Visit
Lost to Follow-up
Missed Visit
a
See Appendix 2.1 for the data listing and evaluability memo for details.
b
Three subjects failed to present for product distribution visit: Subject 3007 voluntarily withdrew
from the study, Subjects 3013 and 3041 were lost to follow-up.
c
“+” indicates that the subject was excluded from the evaluable population at the indicated visit
and all subsequent visits.
134
TABLE 4
BASELINE DEMOGRAPHIC CHARACTERISTICSa,b
ALL SUBJECTS TREATED
BASELINE
CHARACTERISTIC/
STATISTIC
AGE (YEARS)
Mean (SD)
Minimum-Maximum
COLGATE
SIMPLY WHITE
(n = 25)c
EXPERIMENTAL
FILM
(n = 22)c
OVERALL
(n = 47)c
TWOSIDED
p-VALUE
36.9 (13.02)
21 - 65
32.6 (11.72)
22 - 70
34.9 (12.48)
21 - 70
0.2446 f
15 (60.0%)
10 (40.0%)
15 (68.2%)
7 (31.8%)
30 (63.8%)
17 (36.2%)
0.7617 g
1 (4.0%)
7 (28.0%)
15 (60.0%)
1 (4.0%)
1 (4.0%)
2 (9.1%)
5 (22.7%)
13 (59.1%)
1 (4.5%)
1 (4.5%)
3 (6.4%)
12 (25.5%)
28 (59.6%)
2 (4.3%)
2 (4.3%)
0.9463 g
22 (88.0%)
3 (12.0%)
20 (90.9%)
2 (9.1%)
42 (89.4%)
5 (10.6%)
1.0000 g
2 (8.0%)
23 (92.0%)
3 (13.6%)
19 (86.4%)
5 (10.6%)
42 (89.4%)
0.6536 g
2.0
0-8
2.0
0 - 14
2.0
0 - 14
0.7502 h
SEX
Female d
Male d
RACE
Asian d
Black d
Caucasian d
Hispanic d
Multi - racial d
SMOKER
No d
Yes d
COFFEE/TEA/COLA
DRINKERe
No d
Yes d
NUMBER OF DRINKS PER
DAY
Median
Minimum-Maximum
a
See Appendices 2.1, 3.2, and 4.2 for the data listing, statistical analysis program, and output, respectively.
b
Demographics were collected at the baseline visit.
c
n = number of treated subjects in each treatment group and overall.
d
Number and percent of subjects in each category.
e
A drink consists of a cup for coffee or tea or a 12 ounce can of dark cola.
f
Two-sided p-value for the treatment comparison from a two-sample t-test.
g
Two-sided p-value for the treatment comparison from Fisher's Exact test.
h
Two-sided p-value for the treatment comparison from an exact Wilcoxon rank-sum test.
135
TABLE 5
DESCRIPTIVE SUMMARYa
BASELINE COLOR VALUES
ALL SUBJECTS TREATED
COLOR VALUE /
TREATMENT
N
MINIMUM
MEDIAN
MAXIMUM
Colgate Simply White
25
13.79
17.57
21.58
Experimental Film
22
15.27
17.63
20.64
Colgate Simply White
25
66.94
73.68
77.43
Experimental Film
22
68.10
73.91
78.73
25
5.30
6.70
9.57
6.78 (0.919)
22
4.88
6.61
7.79
6.52 (0.814)
25
27.58
32.18
40.25
22
26.95
32.67
37.60
MEAN (SD)
P-VALUEb
b*
17.89
(2.059)
17.67
(1.598)
0.6825
L*
a*
Colgate Simply
White
Experimental Film
W*
Colgate Simply
White
Experimental Film
73.14
(2.932)
73.67
(2.382)
33.01
(3.417)
32.42
(2.406)
a
See Appendices 2.1, 3.3, and 4.3 for the data listing, statistical analysis program, and output, respectively.
b
Two-sided p-value for the treatment comparison from a two-sample t-test.
136
0.5026
0.3052
0.5017
TABLE 6
DESCRIPTIVE SUMMARYa
b*
EVALUABLE SUBJECTS
CHANGE FROM BASELINE
COLOR VALUE /
TREATMENT
PVALU
MEAN
(SD)
MINI
MUM
MEDIA
MAXI
N
MUM
MEAN
(SD)
23
17.69
(2.097)
-0.370
0.67
2
-0.257
(0.532)
0.030
5
20
17.14
(1.484)
1.21
4
1.93
5
-0.529
0.11
7
-0.660
(0.592)
<
0.000
1
23
17.84
(2.094)
-0.270
0.86
0
-0.135
(0.516)
0.221
1
21
16.95
(1.466)
1.15
3
2.17
4
-0.636
0.77
5
-0.677
(0.682)
0.000
2
18
17.93
(2.006)
-0.260
0.68
5
-0.232
(0.587)
0.111
5
21
17.03
(1.422)
1.30
3
2.07
4
-0.771
0.72
7
-0.741
(0.765)
0.000
3
N
Eb
WEEK 2
Colgate
Simply White
Experimental
Film
WEEK 3
Colgate
Simply White
Experimental
Film
WEEK 4
Colgate
Simply White
Experimental
Film
a
See Appendices 2.1, 3.4, and 4.4 for the data listing, statistical analysis program, and output,
respectively.
b
Two-sided p-value for the mean color change from screening using the one-sample t-test.
137
TABLE 7
DESCRIPTIVE SUMMARYa
L*
EVALUABLE SUBJECTS
CHANGE FROM BASELINE
COLOR VALUE /
TREATMENT
N
MEAN
(SD)
MINIMU
MAXIMU
M
MEDIAN
M
73.14
(3.142)
74.19
(2.124)
-1.242
0.058
0.864
-0.126
0.869
1.554
73.15
(3.145)
74.65
(2.430)
-0.886
0.137
1.071
-0.172
1.149
3.019
73.74
(3.286)
74.49
(2.111)
-1.291
0.420
1.081
0.160
0.903
2.463
MEAN
(SD)
PVALUEb
WEEK 2
Colgate Simply
White
Experimental
Film
WEEK 3
Colgate Simply
White
Experimental
Film
WEEK 4
23
20
23
21
Colgate Simply
White
18
Experimental
Film
21
0.046
(0.600)
0.702
(0.534)
0.7189
0.141
(0.452)
1.079
(0.745)
0.1477
0.264
(0.550)
1.064
(0.638)
0.0575
<
0.0001
<
0.0001
<
0.0001
a
See Appendices 2.1, 3.4, and 4.4 for the data listing, statistical analysis program, and output, respectively.
b
Two-sided p-value for the mean color change from screening using the one-sample t-test.
138
TABLE 8
DESCRIPTIVE SUMMARYa
a*
EVALUABLE SUBJECTS
CHANGE FROM BASELINE
COLOR VALUE /
TREATMENT
MINIMU
P-
MAXIMU
N
MEAN (SD)
M
MEDIAN
M
MEAN (SD)
VALUEb
23
6.71
(0.846)
6.15
(0.786)
-0.943
-0.084
0.356
0.0163
-0.871
-0.472
0.125
-0.151
(0.279)
-0.398
(0.310)
6.82
(0.913)
6.25
(0.790)
-0.715
-0.062
0.558
0.6119
-0.666
-0.315
0.533
-0.031
(0.293)
-0.252
(0.333)
6.80
(0.926)
6.18
(0.790)
-1.026
-0.094
0.287
0.0836
-1.132
-0.428
0.290
-0.136
(0.314)
-0.370
(0.382)
WEEK 2
Colgate
White
Simply
Experimental
Film
WEEK 3
Colgate
White
Simply
Experimental
Film
WEEK 4
Colgate
White
Simply
Experimental
Film
20
23
21
18
21
a
See Appendices 2.1, 3.4, and 4.4 for the data listing, statistical analysis program, and output, respectively.
b
Two-sided p-value for the mean color change from screening using the one-sample t-test.
139
<
0.0001
0.0025
0.0003
TABLE 9
DESCRIPTIVE SUMMARYa
W*
EVALUABLE SUBJECTS
CHANGE FROM BASELINE
COLOR VALUE /
TREATMENT
MINIMU
P-
MAXIMU
N
MEAN (SD)
M
MEDIAN
M
MEAN (SD)
VALUEb
23
32.88
(3.638)
31.64
(2.060)
-1.234
-0.270
0.927
0.0992
-2.280
-0.833
-0.128
-0.212
(0.591)
-1.012
(0.694)
32.98
(3.637)
31.18
(2.447)
-1.145
-0.227
0.744
0.0724
-3.530
-1.232
-0.026
-0.199
(0.505)
-1.302
(0.879)
32.54
(3.737)
31.33
(2.077)
-1.471
-0.384
0.351
0.0029
-2.704
-1.221
-0.090
-0.367
(0.449)
-1.348
(0.825)
WEEK 2
Colgate
White
Simply
Experimental Film
20
<
0.0001
WEEK 3
Colgate
White
Simply
Experimental Film
23
21
<
0.0001
WEEK 4
Colgate
White
Simply
Experimental Film
18
21
a
See Appendices 2.1, 3.4, and 4.4 for the data listing, statistical analysis program, and output, respectively.
b
Two-sided p-value for the mean color change from screening using the one-sample t-test.
140
<
0.0001
TABLE 10
DESCRIPTIVE SUMMARYa
E*
EVALUABLE SUBJECTS
CHANGE FROM BASELINE
COLOR VALUE /
TREATMENT
N
MINIMUM
MEDIAN
MAXIMUM
MEAN (SD)
P-VALUEb
23
0.107
0.759
1.706
< 0.0001
20
0.238
1.099
2.371
0.796
(0.392)
1.172
(0.656)
23
0.168
0.672
1.247
< 0.0001
21
0.342
1.353
3.534
0.693
(0.309)
1.463
(0.809)
18
0.358
0.688
2.102
< 0.0001
21
0.271
1.272
2.815
0.827
(0.415)
1.501
(0.825)
WEEK 2
Colgate Simply White
Experimental Film
< 0.0001
WEEK 3
Colgate Simply White
Experimental Film
< 0.0001
WEEK 4
Colgate Simply White
Experimental Film
a
See Appendices 2.1, 3.4, and 4.4 for the data listing, statistical analysis program, and output, respectively.
b
Two-sided p-value for the mean color change from screening using the one-sample t-test.
141
< 0.0001
TABLE 11
TREATMENT COMPARISONS
ANALYSIS OF COVARIANCEa
MEAN b* ADJUSTED FOR BASELINE AND AGE
EVALUABLE SUBJECTS
TREATMENT COMPARISON
N
BASELINE
MEAN (SE)
ADJUSTED MEAN
CHANGE FROM
BASELINE (SE)b
TREATMENT
DIFFERENCE
(SE)
p-VALUEc
Colgate Simply White
23
17.948 (0.446)
-0.230 (0.116)
0.462 (0.173)
0.0109
Experimental Film
20
17.805 (0.356)
-0.691 (0.124)
Colgate Simply White
23
17.974 (0.443)
-0.111 (0.123)
0.594 (0.180)
0.0021
Experimental Film
21
17.629 (0.355)
-0.705 (0.129)
Colgate Simply White
18
18.161 (0.489)
-0.177 (0.152)
0.610 (0.209)
0.0060
Experimental Film
21
17.775 (0.340)
-0.788 (0.140)
VISIT/
TREATMENT GROUP
WEEK 2
WEEK 3
WEEK 4
a
See Appendices 2.1, 3.5, and 4.5 for the data listing, statistical analysis program, and output, respectively.
b
Means adjusted for baseline b* value and age.
c
Two-sided p-value for the treatment comparison of the difference in mean change of
142
b*.
TABLE 12
TREATMENT COMPARISONS
ANALYSIS OF COVARIANCEa
MEAN L* ADJUSTED FOR BASELINE AND AGE
EVALUABLE SUBJECTS
TREATMENT COMPARISON
N
BASELINE
MEAN (SE)
ADJUSTED MEAN
CHANGE FROM
BASELINE (SE)b
TREATMENT
DIFFERENCE
(SE)
p-VALUEc
Colgate Simply White
23
73.092 (0.638)
0.053 (0.123)
-0.640 (0.183)
0.0012
Experimental Film
20
73.490 (0.489)
0.693 (0.132)
Colgate Simply White
23
73.004 (0.627)
0.149 (0.131)
-0.922 (0.192)
< 0.0001
Experimental Film
21
73.566 (0.522)
1.071 (0.137)
Colgate Simply White
18
73.473 (0.711)
0.263 (0.146)
-0.802 (0.201)
0.0003
Experimental Film
21
73.428 (0.469)
1.065 (0.135)
VISIT/
TREATMENT GROUP
WEEK 2
WEEK 3
WEEK 4
a
See Appendices 2.1, 3.5, and 4.5 for the data listing, statistical analysis program, and output, respectively.
b
Means adjusted for baseline L* value and age.
c
Two-sided p-value for the treatment comparison of the difference in mean change of
143
L*.
TABLE 13
TREATMENT COMPARISONS
ANALYSIS OF COVARIANCEa
MEAN a* ADJUSTED FOR BASELINE AND AGE
EVALUABLE SUBJECTS
TREATMENT COMPARISON
N
BASELINE
MEAN (SE)
ADJUSTED MEAN
CHANGE FROM
BASELINE (SE)b
Colgate Simply White
23
6.865 (0.189)
-0.124 (0.058)
Experimental Film
20
6.552 (0.188)
-0.430 (0.062)
Colgate Simply White
23
6.847 (0.192)
-0.017 (0.066)
Experimental Film
21
6.506 (0.181)
-0.268 (0.069)
Colgate Simply White
18
6.940 (0.223)
-0.104 (0.078)
Experimental Film
21
6.553 (0.179)
-0.397 (0.072)
VISIT/
TREATMENT GROUP
TREATMENT
DIFFERENCE
(SE)
p-VALUEc
0.307 (0.086)
0.0010
0.251 (0.096)
0.0126
0.293 (0.108)
0.0099
WEEK 2
WEEK 3
WEEK 4
a
See Appendices 2.1, 3.5, and 4.5 for the data listing, statistical analysis program, and output, respectively.
b
Means adjusted for baseline a* value and age.
c
Two-sided p-value for the treatment comparison of the difference in mean change of
144
a*.
TABLE 14
TREATMENT COMPARISONS
ANALYSIS OF COVARIANCEa
MEAN W* ADJUSTED FOR BASELINE AND AGE
EVALUABLE SUBJECTS
TREATMENT COMPARISON
N
BASELINE
MEAN (SE)
ADJUSTED MEAN
CHANGE FROM
BASELINE (SE)b
Colgate Simply White
23
33.096 (0.741)
-0.193 (0.138)
Experimental Film
20
32.647 (0.486)
-1.034 (0.148)
Colgate Simply White
23
33.178 (0.730)
-0.188 (0.152)
Experimental Film
21
32.477 (0.535)
-1.313 (0.159)
Colgate Simply White
18
32.910 (0.842)
-0.325 (0.158)
Experimental Film
21
32.681 (0.463)
-1.385 (0.146)
VISIT/
TREATMENT GROUP
TREATMENT
DIFFERENCE
(SE)
p-VALUEc
0.841 (0.205)
0.0002
1.125 (0.222)
< 0.0001
1.060 (0.217)
< 0.0001
WEEK 2
WEEK 3
WEEK 4
a
See Appendices 2.1, 3.5, and 4.5 for the data listing, statistical analysis program, and output, respectively.
b
Means adjusted for baseline W* value and age.
c
Two-sided p-value for the treatment comparison of the difference in mean change of
145
W *.
TABLE 15
TREATMENT COMPARISONS
ANALYSIS OF COVARIANCEa
MEAN E* ADJUSTED FOR BASELINE AND AGE
EVALUABLE SUBJECTS
TREATMENT COMPARISON
VISIT/
TREATMENT GROUP
MEAN CHANGE
FROM BASELINE
N
(SE)
TREATMENT
DIFFERENCE (SE)
Colgate Simply White
23
0.773 (0.112)
-0.426 (0.168)
0.0154
Experimental Film
20
1.199 (0.120)
Colgate Simply White
23
0.692 (0.129)
-0.772 (0.190)
0.0002
Experimental Film
21
1.464 (0.136)
Colgate Simply White
18
0.788 (0.160)
-0.746 (0.222)
0.0020
Experimental Film
21
1.534 (0.147)
p-VALUEb
WEEK 2
WEEK 3
WEEK 4
a
See Appendices 2.1, 3.5, and 4.5 for the data listing, statistical analysis program, and output,
respectively.
b
Means adjusted for baseline b*, L*, and a* values as well as age.
c
Two-sided p-value for the treatment comparison of the difference in mean change of
146
E*.
TABLE 16
END-OF-TREATMENT COMPARISONS – ANALYSIS OF COVARIANCE a
EXPERIMENTAL FILM AT WEEK 4 VS COLGATE SIMPLY WHITE AT WEEK 3
ADJUSTED FOR BASELINE AND AGE
EVALUABLE SUBJECTS
TREATMENT COMPARISON
ADJUSTED MEAN
TREATMENT
CHANGE FROM
DIFFERENCE
VISIT/
BASELINE
BASELINE (SE)b
p-VALUEc
TREATMENT GROUP
N
MEAN (SE)
(SE)
b*
Colgate Simply White
23
17.974 (0.443)
-0.098 (0.131)
Experimental Film
21
17.775 (0.340)
-0.782 (0.137)
Colgate Simply White
23
73.004 (0.627)
0.145 (0.118)
Experimental Film
21
73.428 (0.469)
1.061 (0.124)
Colgate Simply White
23
6.847 (0.192)
-0.010 (0.070)
Experimental Film
21
6.553 (0.179)
-0.394 (0.073)
Colgate Simply White
23
33.178 (0.730)
-0.172 (0.142)
Experimental Film
21
32.681 (0.463)
-1.377 (0.149)
0.684 (0.191)
0.0009
-0.916 (0.173)
< 0.0001
0.384 (0.102)
0.0005
1.205 (0.208)
< 0.0001
-0.855 (0.193)
< 0.0001
L*
a*
W*
E*
Colgate Simply White
23
0.670 (0.131)
Experimental Film
21
1.526 (0.137)
a
See Appendices 2.1, 3.6, and 4.6 for the data listing, statistical analysis program, and output, respectively.
b
Means adjusted for baseline color and age.
c
Two-sided p-value for the treatment comparison of the difference in mean color change from baseline.
147
TABLE 17
ADDITIONAL TREATMENT COMPARISONS – ANALYSIS OF COVARIANCE a
EXPERIMENTAL FILM AT WEEK 2 VS COLGATE SIMPLY WHITE AT WEEK 3
ADJUSTED FOR BASELINE AND AGE
EVALUABLE SUBJECTS
TREATMENT COMPARISON
ADJUSTED MEAN
TREATMENT
CHANGE FROM
DIFFERENCE
VISIT/
BASELINE
BASELINE (SE)b
p-VALUEc
TREATMENT GROUP
N
MEAN (SE)
(SE)
b*
Colgate Simply White
23
17.974 (0.443)
-0.108 (0.114)
Experimental Film
20
17.805 (0.356)
-0.691 (0.122)
Colgate Simply White
23
73.004 (0.627)
0.152 (0.106)
Experimental Film
20
73.490 (0.489)
0.690 (0.114)
Colgate Simply White
23
6.847 (0.192)
-0.014 (0.062)
Experimental Film
20
6.552 (0.188)
-0.419 (0.067)
Colgate Simply White
23
33.178 (0.730)
-0.185 (0.129)
Experimental Film
20
32.647 (0.486)
-1.028 (0.138)
0.583 (0.170)
0.0014
-0.538 (0.157)
0.0015
0.405 (0.093)
< 0.0001
0.843 (0.192)
< 0.0001
-0.501 (0.159)
0.0032
L*
a*
W*
E*
Colgate Simply White
23
0.683 (0.106)
Experimental Film
20
1.183 (0.114)
a
See Appendices 2.1, 3.7, and 4.7 for the data listing, statistical analysis program, and output, respectively.
b
Means adjusted for baseline color and age.
c
Two-sided p-value for the treatment comparison of the difference in mean color change from baseline.
148
TABLE 18.1
POSSIBLE OR PROBABLE TREATMENT RELATED (BY WEEK 4)
ORAL IRRITATION OR TOOTH SENSITIVITYa
ALL SUBJECTS TREATED
COLGATE SIMPLY EXPERIMENTAL
WHITE
FILM
b
(n = 25)
(n = 22)b
OVERALL
(n = 47)b
NO. SUBJ. (%
SUBJ.)c
NO. SUBJ. (%
SUBJ.)c
NO. SUBJ. (%
SUBJ.)c
Oral Irritation
0 (0)
8 (36.4)
8 (17.0)
Tooth Sensitivity
0 (0)
4 (18.2)
4 (8.5)
0 (0)
2 (9.1)
2 (4.3)
0 (0)
10 (45.5)
10 (21.3)
0 (0)
1 (4.5)
1 (2.1)
Oral irritation
0 (0)
8 (36.4)
8 (17.0)
Tooth Sensitivity
0 (0)
4 (18.2)
4 (8.5)
0 (0)
2 (9.1)
2 (4.3)
0 (0)
10 (45.5)
10 (21.3)
AE
SOURCE/AE
CLASSIFICATION
SELF REPORTED
Oral Irritation and
Tooth Sensitivity
Oral Irritation or Tooth
Sensitivity
OBSERVED
Oral Irritation
EITHER OBSERVED
SELF REPORTED
OR
Oral irritation and
Tooth Sensitivity
Oral irritation or Tooth
Sensitivity
a
See Appendices 2.1, 3.8, and 4.8 for the data listing, statistical analysis program, and
output, respectively.
b
Number of subjects randomized in each group and overall.
c
Number (Percent) of randomized subjects with the indicated AE (out of the number reported
in each group).
149
TABLE 18.2
POSSIBLE OR PROBABLE TREATMENT RELATED (BY WEEK 2)
ORAL IRRITATION OR TOOTH SENSITIVITYa
ALL SUBJECTS TREATED
COLGATE SIMPLY
WHITE
(n = 25)b
EXPERIMENTAL
FILM
(n = 22)b
OVERALL
(n = 47)b
NO. SUBJ. (% SUBJ.)c
NO. SUBJ. (%
SUBJ.)c
NO. SUBJ. (%
SUBJ.)c
Oral Irritation
0 (0)
2 (9.1)
2 (4.3)
Tooth Sensitivity
0 (0)
2 (9.1)
2 (4.3)
0 (0)
0 (0)
0 (0)
0 (0)
4 (18.2)
4 (8.5)
0 (0)
1 (4.5)
1 (2.1)
Oral irritation
0 (0)
2 (9.1)
2 (4.3)
Tooth Sensitivity
0 (0)
2 (9.1)
2 (4.3)
0 (0)
0 (0)
0 (0)
0 (0)
4 (18.2)
4 (8.5)
AE SOURCE/AE CLASSIFICATION
SELF REPORTED
Oral Irritation and Tooth
Sensitivity
Oral Irritation or Tooth
Sensitivity
OBSERVED
Oral Irritation
EITHER OBSERVED
REPORTED
OR
Oral irritation and Tooth
Sensitivity
Oral irritation or Tooth
Sensitivity
SELF
a
See Appendices 2.1, 3.9, and 4.9 for the data listing, statistical analysis program, and output, respectively.
b
Number of subjects randomized in each group and overall.
c
Number (Percent) of randomized subjects with the indicated AE (out of the number reported in each group).
150
TABLE 19.1
SUMMARY OF ADVERSE EVENTSa (BY WEEK 4)
ALL SUBJECTS TREATED
COLGATE SIMPLY
WHITE
(n = 25)b
EXPERIMENTAL FILM
(n = 22)b
OVERALL
(n = 47)b
NO.
SUBJ.
(%
SUBJ.)c
NO. AES
(%
AES)d
NO.
SUBJ.
(%
SUBJ.)c
NO. AES
(%
AES)d
NO. SUBJ.
(%
SUBJ.)c
NO. AES
(% AES)d
Serious AEs
0(0)
0(0)
0(0)
0(0)
0(0)
0(0)
Mild AEs
1(4)
1(100)
10(45)
13(100)
11(23)
14(100)
Moderate AEs
0(0)
0(0)
0(0)
0(0)
0(0)
0(0)
Severe AEs
0(0)
0(0)
0(0)
0(0)
0(0)
0(0)
Not Related
0(0)
0(0)
0(0)
0(0)
0(0)
0(0)
Doubtful Related
1(4)
1(100)
1(5)
1(8)
2(4)
2(14)
Possibly Related
0(0)
0(0)
7(32)
8(62)
7(15)
8(57)
Probably Related
0(0)
0(0)
4(18)
4(31)
4(9)
4(29)
1(4)
1(100)
10(45)
13(100)
11(23)
14(100)
Total
Mean number of AEs per
subject (all subjects)
Mean number of AEs per
subject (only subjects with
AEs)
0.04
0.59
0.3
1
1.3
1.27
a
See Appendices 2.1, 3.10, and 4.10 for the data listing, statistical analysis program, and output, respectively.
b
n = number of subjects within the specified treatment group or overall.
c
Number (Percent) of subjects with the indicated AE category (out of the number of subjects in each group).
d
Number (Percent) of AEs reported within the category (out of the total number of AEs reported in each group).
151
TABLE 19.2
SUMMARY OF ADVERSE EVENTSa (BY WEEK 2)
ALL SUBJECTS TREATED
COLGATE SIMPLY
WHITE
(n = 25)b
EXPERIMENTAL FILM
(n = 22)b
OVERALL
(n = 47)b
NO. SUBJ.
(%
SUBJ.)c
NO. AES
(%
AES)d
NO.
SUBJ.
(%
SUBJ.)c
NO. AES
(%
AES)d
NO. SUBJ.
(%
SUBJ.)c
NO. AES
(% AES)d
Serious AEs
0(0)
0(0)
0(0)
0(0)
0(0)
0(0)
Mild AEs
0(0)
0(0)
5(23)
5(100)
5(11)
5(100)
Moderate AEs
0(0)
0(0)
0(0)
0(0)
0(0)
0(0)
Severe AEs
0(0)
0(0)
0(0)
0(0)
0(0)
0(0)
Not Related
0(0)
0(0)
0(0)
0(0)
0(0)
0(0)
Doubtful Related
0(0)
0(0)
1(5)
1(20)
1(2)
1(20)
Possibly Related
0(0)
0(0)
0(0)
0(0)
0(0)
0(0)
Probably Related
0(0)
0(0)
4(18)
4(80)
4(9)
4(80)
0(0)
0(0)
5(23)
5(100)
5(11)
5(100)
Total
Mean number of AEs per
subject (all subjects)
Mean number of AEs per
subject (only subjects with
AEs)
0
0.23
0.11
0
1
1
a
See Appendices 2.1, 3.11, and 4.11 for the data listing, statistical analysis program, and output, respectively.
b
n = number of subjects within the specified treatment group or overall.
c
Number (Percent) of subjects with the indicated AE category (out of the number of subjects in each group).
d
Number (Percent) of AEs reported within the category (out of the total number of AEs reported in each group).
152
TABLE 20
ADVERSE EVENTS IN DECREASING ORDER OF INCIDENCE
BY COSTART PREFERRED TERM AND TREATMENT GROUPa
ALL SUBJECTS TREATED
COSTART
PREFERRED TERM
COLGATE SIMPLY
WHITE
(n = 25)b
EXPERIMENTAL FILM
(n = 22)b
NO. SUBJ.
(% SUBJ.)c
NO. AES
(% AES)d
NO. SUBJ. NO. AES
(% SUBJ.)c (% AES)d
GINGIVITIS
1(4)
1(100)
6(27)
HYPERESTHESIA
0(0)
0(0)
CHEILITIS
0(0)
STOMATITIS
TOTAL
OVERALL
(n = 47)b
NO. SUBJ.
(% SUBJ.)c
NO. AES
(% AES)d
6(46)
7(15)
7(50)
5(23)
5(38)
5(11)
5(36)
0(0)
1(5)
1(8)
1(2)
1(7)
0(0)
0(0)
1(5)
1(8)
1(2)
1(7)
1(4)
1(100)
10(45)
13(100)
11(23)
14(100)
a
See Appendices 2.1, 3.12, and 4.12 for the data listing, statistical analysis program, and output, respectively.
b
n = number of subjects within the specified treatment group or overall.
c
Number (Percent) of subjects with the indicated AE category (out of the number of subjects in each group).
d
Number (Percent) of AEs reported within the category (out of the total number of AEs reported in each group).
153
TABLE 21
MILD ADVERSE EVENTS
BY COSTART PREFERRED TERM AND TREATMENT GROUPa
ALL SUBJECTS TREATED
COSTART
PREFERRED TERM
COLGATE SIMPLY
WHITE
(n = 25)b
EXPERIMENTAL FILM
(n = 22)b
NO. SUBJ.
(% SUBJ.)c
NO. AES
(% AES)d
NO. SUBJ. NO. AES
(% SUBJ.)c (% AES)d
GINGIVITIS
1(4)
1(100)
6(27)
HYPERESTHESIA
0(0)
0(0)
CHEILITIS
0(0)
STOMATITIS
TOTAL
OVERALL
(n = 47)b
NO. SUBJ.
(%
SUBJ.)c
NO. AES
(% AES)d
6(46)
7(15)
7(50)
5(23)
5(38)
5(11)
5(36)
0(0)
1(5)
1(8)
1(2)
1(7)
0(0)
0(0)
1(5)
1(8)
1(2)
1(7)
1(4)
1(100)
10(45)
13(100)
11(23)
14(100)
a
See Appendices 2.1, 3.12, and 4.12 for the data listing, statistical analysis program, and output, respectively.
b
n = number of subjects within the specified treatment group or overall .
c
Number (Percent) of subjects with the indicated AE category (out of the number of subjects in each group).
d
Number (Percent) of AEs reported within the category (out of the total number of AEs reported in each group).
154
TABLE 22
NOT OR DOUBTFUL TREATMENT RELATED ADVERSE EVENTS
BY COSTART PREFERRED TERM AND TREATMENT GROUP a
ALL EVALUABLE SUBJECTS
COSTART
PREFERRED TERM
COLGATE SIMPLY
WHITE
(n = 25)b
EXPERIMENTAL FILM
(n = 22)b
NO. SUBJ.
(% SUBJ.)c
NO. AES
(% AES)d
NO. SUBJ. NO. AES
(% SUBJ.)c (% AES)d
GINGIVITIS
1(4)
1(100)
0(0)
HYPERESTHESIA
0(0)
0(0)
TOTAL
1(4)
1(100)
OVERALL
(n = 47)b
NO. SUBJ.
(% SUBJ.)c
NO. AES
(% AES)d
0(0)
1(2)
1(7)
1(5)
1(8)
1(2)
1(7)
1(5)
1(8)
2(4)
2(14)
a
See Appendices 2.1, 3.12, and 4.12 for the data listing, statistical analysis program, and output, respectively.
b
n = number of subjects within the specified treatment group or overall.
c
Number (Percent) of subjects with the indicated AE category (out of the number of subjects in each group).
d
Number (Percent) of AEs reported within the category (out of the total number of AEs reported in each group).
155
TABLE 23
POSSIBLE OR PROBABLE TREATMENT RELATED ADVERSE EVENTS
BY COSTART PREFERRED TERM AND TREATMENT GROUPa
ALL SUBJECTS TREATED
COSTART
PREFERRED TERM
COLGATE SIMPLY
WHITE
(n = 25)b
EXPERIMENTAL FILM
(n = 22)b
NO. SUBJ.
(% SUBJ.)c
NO. AES
(% AES)d
NO. SUBJ. NO. AES
(% SUBJ.)c (% AES)d
GINGIVITIS
0(0)
0(0)
6(27)
HYPERESTHESIA
0(0)
0(0)
CHEILITIS
0(0)
STOMATITIS
TOTAL
OVERALL
(n = 47)b
NO. SUBJ.
(% SUBJ.)c
NO. AES
(% AES)d
6(46)
6(13)
6(43)
4(18)
4(31)
4(9)
4(29)
0(0)
1(5)
1(8)
1(2)
1(7)
0(0)
0(0)
1(5)
1(8)
1(2)
1(7)
0(0)
0(0)
10(45)
12(92)
10(21)
12(86)
a
See Appendices 2.1, 3.12, and 4.12 for the data listing, statistical analysis program, and output, respectively.
b
n = number of subjects within the specified treatment group or overall.
c
Number (Percent) of subjects with the indicated AE category (out of the number of subjects in each group).
d
Number (Percent) of AEs reported within the category (out of the total number of AEs reported in each group).
156
Yellowness
Improvement
(–b*) (–b*)
Figure 1:
Adjusted Mean
Yellowness Improvement
1
0 .8
0 .6
0 .4
0 .2
0
Week 2
Week 3
C o lg a te S im p ly W h ite
Week 4
E x p e r im e n ta l F ilm
Lightness
Improvement
(L*) (L*)
Figure 2:
Adjusted Mean
Lightness Improvement
1 .2
1
0 .8
0 .6
0 .4
0 .2
0
Week 2
Week 3
C o lg a te S im p ly W h ite
156
Week 4
E x p e r im e n ta l F ilm
REFERENCES
1. HaywoodVB, Heymann HO. Nightguard vital bleaching. Quintessence Int.
1989; 20:173-6
2. Goldstein RE.In-office bleaching: where we came from, where we are today. Jam Dent
Assoc1997;128:11S-15S
3. BurrellKH.ADA supports vital tooth bleaching –but look for the seal. J Am Dent
Assoc1997 128:3S-5S.
4. CrollTP, SasaIS.Carbemide peroxide of teeth with dentiogenisis imperfecta
discoloration: report of a case. Quintessence Int. 1995; 26:683-6
5. Haywood VB. Night guard bleaching to lighten a restored, nonvital discolored tooth.
Compend Continuing Education Dent 1998;19:810-3
6. Frazier KB. Nightguard bleaching to lighten a restored, nonvital discolored tooth.
Compend Contin Educ Dent 1998; 19:810-3
7. Small BW. The application and integration of at-home bleaching into private dental
practice. Compend Contin Educ Dent 1998;19:799-806
8. HaywoodVB, Robinson FG.Vital tooth bleaching with nightgaurd vital bleaching.
Curr.Opin CosmeticDent1997;4:45-52
9. KugelG,PerryRD, Hoang E,Scherer W.Effective tooth bleaching in 5days: using a
combined in office and at home bleaching system . Comp contin Educ Dent
1997 ;18:378-83
10. Kugel G Over the counter tooth whitening Systems Compendium April 2003; 24;4A
376-82
11. Donly KJ, DonlyAS, BaharlooL, et al. Tooth whitening in children, Compend Contin
Edu Dent. 2002; 3:22-27.
157
Chapter 9
Maintenance of Whitening
Clinical Study to Evaluate the Maintenance of Whitening after Bleaching Treatment
Abstract
A randomized, parallel, examiner-blind clinical study was conducted to examine the ability of 2
toothbrushes to maintain teeth whitening after at-home bleaching. Forty subjects used a 15%
carbamide peroxide tray bleaching system at home for 2 weeks per the manufacturer’s instructions
and then were randomly assigned to use either the Sonicare® Advance power toothbrush or a
manual toothbrush as part of their home oral hygiene routine for 6 months. The color of the labial
surfaces of the subjects’ maxillary anterior dentition was assessed before bleaching and
immediately, 2 months, 3 months, and 6 months after bleaching. Color was assessed by
comparison with Vita® Classical shade tabs and by digital image analysis in the CIE L*a*b* color
space. Both groups demonstrated a rebound effect at the 2-month visit and beyond, with mean Vita
shade scores significantly higher than immediately after bleaching. At the 6-month evaluation, there
was a significant difference in the amount of rebound in each group. Specifically, the rebound of the
Sonicare brush group was on average 1.12 Vita shades less than that of the manual brush group.
The 6-month difference was confirmed through digital image analysis, with the Sonicare brush
group 4.8 L* units lighter, corresponding to 2 Vita shades, and 2.1 b* units less yellow than the
manual brush group. This clinical trial demonstrates that the Sonicare Advance toothbrush better
maintains whitening after bleaching treatment than a manual toothbrush.
158
Learning Objectives
After reading this article, the reader should be able to:

Understand maintenance of whitening after bleaching using an electric toothbrush.

To demonstrate that significant rebound can occur post bleaching.

To demonstrate the use of digital photography in determining L* a* b* values
The use of peroxide to whiten teeth has a lengthy history dating to the early 20th century. With the
advent of patient-applied kits, bleaching has become both common and popular, and use of
peroxide is now generally recognized as a safe and effective method for tooth whitening.1-3 There
are a variety of indications for bleaching single or multiple teeth, including staining from
chromogenic foods, dental fluorosis, tetracycline staining, and devital discolored teeth.4-7 Up to 90%
of U.S. dental practices offer vital tooth bleaching, and in some dental practices, up to one-fifth of
patients undergo bleaching.8-9
Concentrations of up to 35% peroxide are used alone or in combination with various agents for
tooth bleaching. Delivery is via in-office, at-home, or combination regimens, with or without
professional supervision.10,11 Of these, bleaching is most commonly accomplished at home over a
period of a few weeks.12 Treatment duration may vary based on the degree of staining because
whitening is reported to be a product of peroxide concentration and contact time.13 For some
difficult stains like tetracycline, daily bleaching for up to 6 months may be indicated.14
Treatment is generally effective, with 90% or more of clinical trial subjects experiencing initial
whitening.15,16 The efficacy of a bleaching treatment may be established through first or second
person observation or various technical methods. Clinical trials most commonly include the use of a
shade guide, colorimeter, or computer digitization to measure color change over time.17,18 In these
studies, efficacy is commonly monitored for 6 months.13,16 While there may be some shade
deterioration over time, most patients experience a whitening effect that may persist, to at least
159
some degree, 3 years or more after initial treatment.13,15 In addition to the cosmetic benefits,
bleaching is believed to contribute to various intangibles, including heightened patient involvement
and increased interest in dentistry and oral health.7,8
Some patients who have undergone bleaching are concerned with the stability of their newly
bleached teeth. Practitioners often have no real answer for the patient concerning the stability of
bleached dentition. Rebound, the re-coloring of bleached teeth, is assumed to be a multifactor
process. The factors may include the structure and composition of an individual’s dentin and
enamel, the types of food and drink he or she consumes, and the oral hygiene routine. In the
current study, we examined the impact of the oral hygiene routine. Specifically, we assessed the
ability of the Sonicare® Advance powered toothbrusha to prevent rebound compared with a
standard manual toothbrush.
The Sonicare Advance toothbrush operates with high-frequency bristle movement (260 Hz; 31,000
brush strokes per minute). In addition to cleaning by direct bristle contact, the Sonicare Advance
generates significant fluid activity, which has been hypothesized as the reason for the brush’s ability
to clean beyond the reach of the bristles as demonstrated in several laboratory studies.19-22 The
Sonicare Advance also has been shown to remove stains in clinical and laboratory studies,
removing more stain in vivo than a manual toothbrush.23, 24 A study of the brush’s ability to inhibit
rebound after bleaching, a natural extension of this earlier work, was the focus of the current study.
Methods and Materials
Population Selection
Potential subjects were screened and enrolled in this clinical trial at Tufts University, Boston,
Massachusetts, after meeting the inclusion/exclusion criteria. At screening, written informed
consent was obtained from each subject after review of the study design and test regimen. Using
the Vita® Classical shade guideb, Vita shade scores were recorded for each subject on labial
160
surfaces of the maxillary anterior teeth. Subjects with individual tooth scores of A2 or darker were
eligible for enrollment. Dentinal sensitivity, use of tobacco products, the presence of tetracycline
stain, dental fluorosis, atypical nonuniform stain, fixed orthodontic appliances, and large intake of
stain-inducing beverages were all reasons for exclusion. Subjects who qualified and agreed to
participate were enrolled in the study. At the postbleaching evaluation, subjects exhibiting a
decrease of at least 2 Vita shades were allowed to continue in the study; all subjects met this
requirement.
STUDY DESIGN
This was an examiner blind, parallel-group, 6-month study with clinical evaluations both before
(prebleaching baseline) and after (postbleaching baseline) a two-week bleaching treatment and at
one, 2, 3, and 6 months after the end of bleaching. At each visit, oral soft and hard tissues were
examined, subjects were questioned about presence or absence of tooth hypersensitivity to
thermal, air, or other such stimuli, and a Vita shade assessment of the labial surfaces of the anterior
maxillary teeth was recorded. A subset of 14 subjects, 7 per treatment group, was randomly
selected for digital image analysis. For subjects in this subset, digital images of the maxillary
anterior teeth also were captured at each visit.
At the screening appointment, impressions of the maxillary teeth were taken and used to fabricate
the bleaching trays. The trays were distributed at the first study visit, baseline prebleaching, along
with a standard home bleaching system of 15% carbamide peroxide (Opalescencec). All subjects
were given a standard manual toothbrush (Crest® Extra Softd) and sodium fluoride dentifrice (Crest
Cavity Protectiond) for use during the bleaching period. Subjects received oral and written
instructions on the bleaching system’s recommended use and the Bass brushing technique.25
Subjects were asked to use the bleaching trays twice per day for 60 minutes at each use and to
brush with the manual toothbrush twice per day for 2 minutes at each brushing. At the
postbleaching baseline appointment 2 weeks later, bleaching trays were collected and study
161
toothbrushes were distributed according to a stratified randomization designed to foster similar
shade distributions at prebleaching baseline (low / medium / high Vita shade score means) in each
brush group. Subjects exhibiting a mean Vita shade score improvement of at least 2.0 were
permitted to continue in the study. Subjects in one group were asked to continue using the manual
toothbrush as previously instructed. Subjects in the other group were given a Sonicare Advance
toothbrush, instructed in its use according to the manufacturer’s instructions, and asked to use the
toothbrush with the same study dentifrice twice daily for 2 minutes at each brushing.
EFFICACY ASSESSMENTS
Vita Shade Guide Assessment Assessments of tooth color with the Vita Classical shade guide
included the maxillary incisors. The Vita shade guide is a standard scale of multiple tooth-shaped
tabs, each having a different color. Commonly used in dentistry to match artificial crowns to the
natural dentition, the Vita shade guide has been successfully applied in clinical studies to assess
the efficacy of tooth whitening products.4,7-9
All examinations were performed under color balanced lighting conditions using diffused lighting,
with color temperature approximately 5500 K. To reduce variation, all examinations were performed
in the same operatory—and thus under the same lighting conditions—whenever possible. The
operatory colors were neutral, and both the evaluator and subject were instructed to avoid wearing
bright clothing. A blue bib was draped over all subjects, and they were instructed to remove jewelry,
eyeglasses, lipstick, and anything else that could interfere with shade selection. Without drying the
teeth, the evaluators judged tooth color by selecting the closest shade tab on the guide. Between
individual observations, the evaluators looked at a light blue card for a few seconds. Assessment of
brushing treatment efficacy was performed by a rank ordering of shade tabs arranged from dark to
light according to the rank ordering suggested by the manufacturer (Table 1).
To ensure maximum integrity of the data, only 2 evaluators performed Vita shade assessments in
the study. Before the screening visit, the clinical evaluators examined a subset of subjects for tooth
162
color using the Vita shade guide to establish intra-evaluator repeatability. Intra-examiner kappa
statistics at 3 months were 1.00 (95% confidence interval (CI): 0.73, 1.00) and 0.88 (95% CI: 0.62,
1.00) for the examiners, and the inter-examiner kappa for the 2 examiners was 0.88.
DIGITAL IMAGING
Using existing technologies of digital photography and photographic analysis software used in the
printing industry, it is possible to assess the color of teeth that currently cannot be matched by
existing shade guides, making it possible to assess differences as small as one-eighth of a Vita
shade.26 In recent years the CIE L*a*b* color space has been accepted as the benchmark for
assessing color.27 This space covers the entire range of color seen by the human eye. The L*a*b*
color model consists of a luminance component, L* (black to white), and 2 chromatic components,
a* (green to red) and b* (blue to yellow). Figure 1 presents the CIE L*a*b* scale as a 3-dimensional
visualization. The subjects’ baseline post bleaching and 6-month rebound images were
photographed using the same standard digital camera under lighting conditions identical to those
used during the Vita shade assessments. Subjects were positioned with the central incisal edge 9
inches from the lens of the camera, which was mounted on an axis perpendicular to the facial
surface of the central incisors. Patients were presented edge-to-edge with retractors and were
asked to touch the tip of their tongue to their soft palate. This allowed light to readily pass through
the tooth surface and reduce reflectance from the tongue. The camera’s flash unit was used to
ensure the consistency of light source and an ultraviolet filter was used on the camera to reduce
glossing, which may occur with flash usage, thereby reducing the likelihood of hot spots and
increasing the consistency of color accuracy between images. The camera was plugged into a 120volt power source to ensure a constant flash intensity between images. Vita Classical and 3D
Master shade guides were photographed as well, providing controls to ensure maintenance of
163
photographic settings and quality and to establish a guideline for comparison between the L*a*b*
and Vita shade guide subject data collected.
Adobe Photoshop softwaree was used to generate the L*a*b* scores. To ensure accuracy, 9
locations were sampled on each of the central incisors, lateral incisors and canines of the maxillary
arch, and L*a*b* scores were generated at these points. These data were then averaged to find a
mean color and standard deviation of color on each tooth. A Gaussian blur filter set at 13 units,
which averages color over an entire photo, was then applied to the original digital image. Using this
filtering technique, 4 sampling locations were identified as optimal—the incisal-middle third and the
middle-middle third of the maxillary left central and lateral incisors—because they provided the
same information obtained from sampling the 9 locations without a filter. This allowed for faster
sampling and decreased variability in the data by moderating the color extremes.
Efficacy of the brushing treatment was made by comparison of L*a*b* scores derived from images
captured at the first post bleaching clinical visit (post bleaching baseline) and 3 and 6 months
thereafter. L* and b* are the 2 components of L*a*b* scores most recognized as being influenced
by bleaching treatment, with an increase in L* indicating lightening and a decrease in b* indicating
decreasing yellow and thus decreasing stain.
STATISTICAL ANALYSIS
The primary analysis used linear mixed effect models appropriate for a repeated measures design.
This type of analysis supports the use of incomplete cases and allows for the testing of overall
differences between brushes, overall change over time, and differences in brushes over time. The
primary Vita shade analysis focused on comparing mean Vita shade scores between treatment
groups over time. Secondary Vita shade analysis included comparisons between mean Vita shade
scores of individual teeth over time. The luminance component of the L*a*b* scores generated from
the digital images collected on the subset of 14 subjects was analyzed with 2-sample Student t-
164
tests, comparing differences in L* and b* (post bleaching baseline to 6 months post bleaching)
between groups.
RESULTS
A total of 43 subjects 18 years of age or older and in good health were enrolled in the study. At the
pre-bleaching baseline examination, the groups were comparable in terms of Vita shade scores and
age (Tables 2 and 3). Three subjects did not return after the bleaching treatment and were dropped
from the study, making the total sample size 40. The study sample was composed of 23 women
and 17 men. Thirty-one subjects, 18 from the Sonicare group and 13 from the manual toothbrush
group, returned for all clinical evaluations over the course of the 6-month study. Twelve subjects, 3
from the Sonicare group and 9 from the manual toothbrush group, missed at least 1 visit over the
course of the 6-month study. The mean Vita shade scores over time overall and by individual tooth
are presented in FiFigure 2 and Figure 3, respectively.
After completion of the bleaching treatment, the average shade score in the manual toothbrush
group was approximately 1.3 Vita shades lower than that of the Sonicare group. Clearly the 2
groups responded differently to the bleaching treatment, though both were using the same
dentifrice and manual toothbrush during the bleaching process. To assess the statistical
significance of the observed difference, a 2-sample Student t-test was used to test the null
hypothesis of no difference in mean Vita score between groups after bleaching. Because the result
was not statistically significant (P = .06), the null hypothesis of no difference in mean post bleaching
shade scores between brush groups was accepted.
Results of the linear mixed effects model using the complete case data indicate a statistically
significant effect per visit. With the exception of the 1-month evaluation, all visits were found to have
significantly different mean Vita scores (1 month P = .14; 2 months P < .001; 3 months P = .013; 6
165
months P < .001), relative to the first post bleaching exam. That is, for both brush groups at the 2month visit and beyond, mean Vita shade scores were significantly higher (darker) than
immediately after bleaching. This indicates a rebound effect after 2 months. No statistically
significant effect between groups, or brush type, was found (P = .07). This is not surprising because
the groups were designed to have similar shade levels and this tests the combined group averages
across all visits.
To determine if rebound was affected over time by brush type, the interaction of brush type and visit
was tested. A statistically significant difference was found at the 6-month evaluation (P = .04),
indicating that the brush groups rebounded differently after 6 months of brushing. On average, the
manual brush group rebound was 1.12 Vita shades greater than that of the Sonicare brush group.
The 2-sample Student t-test assessing the mean change in luminance L* between brush groups
(post bleaching baseline to 6 months post bleaching) returned a statistically significant result (P <
.001), indicating teeth darkened with the use of the manual toothbrush compared with the use of the
Sonicare toothbrush. The difference was estimated at –4.8 (95% CI: –6.5, –3.1); that is, after 6
months of toothbrush use, the manual toothbrush group mean was 4.8 L* units darker than the
Sonicare toothbrush group mean. This difference in luminance was equivalent to 2 Vita Classical
shades. The mean change in the blue-yellow axis b* also was assessed with a 2-sample Student ttest (post bleaching baseline to 6 months post bleaching). Again, the Sonicare toothbrush group
showed a statistically significant difference from the manual toothbrush group (P < .001), indicating
less of the yellow component for the Sonicare toothbrush group. The difference between groups
was estimated at 2.1 b* units (95% CI: 0.9 to 3.2). (Table 4)
Three subjects showed signs of gingival sensitivity associated with the bleaching treatment; all
subsequently resolved with the completion of the bleaching treatment. Both brushes had excellent
safety records with no adverse events or abnormal intraoral exams reported after bleaching.
166
Photographs representing the type of changes observed in each group are presented in Figure 4
and Figure 5.
DISCUSSION
The analyses of the digital images and the Vita shade data both show the Sonicare toothbrush to
be superior to a manual toothbrush at maintaining whitening 6 months after bleaching. While this is
the first study examining the effect of Sonicare on maintaining whitening, there are other data on
the effect of a manual toothbrush. Matis and colleagues,28 for example, report an increase of 5.2 L*
units and 2.9 shade guide units only 6 weeks after a 2-week bleaching regimen using 15%
carbamide peroxide. Our results show a more modest but still measurable rebound effect for
manual brushing.
The estimated 6-month Vita shade difference between groups was larger in the digital analysis (2
Vita shades) than in the Vita shade analysis (1.12 Vita shades). This difference in estimates may be
the result of the varying precision and accuracy of the 2 efficacy measures. We additionally note
that the ordering of the Vita Classical shade guide does not follow the order suggested by digital
image analysis of the shade tabs. In particular, ranking the tabs by decreasing luminance L*, that is
the pure value axis of the L*a*b* color sphere, suggests not only that the color tabs are incorrectly
ordered but also that the color change between tabs is nonlinear (Figure 6). Similar observations
have been reported by O’Brien and colleagues29 and Paravina and colleagues.30 These factors also
may contribute to the difference in estimates between the 2 efficacy measures.
The choice of randomization based on pre-bleaching mean Vita scores was made after considering
the alternative of basing the randomization on the post bleaching mean Vita scores. The use of the
former generated treatment groups with similar color shade distribution before bleaching. It was
167
believed that the method would produce groups with similar rebound patterns because the 2 groups
were comparable before bleaching. The latter method would have produced comparable groupings
after bleaching, but would have ignored the initial, pre-bleaching color distributions. This could have
lead to groups with different rebound responses if their initial shade colors were very different.
CONCLUSIONS
The demand for tooth bleaching products and their use by professionals and patients is increasing
every day. Treatment options include in-office bleaching, take-home bleaching, or a combination of
the 2, with or without professional supervision. The take-home system is the most convenient for
patients and professionals alike and proves to be very effective over a period of a few weeks.
Studies have shown that there is some shade rebound over time. The clinician should keep in mind
that the patient’s eating and drinking habits are likely to affect rebound as extrinsic staining can be
caused by the use of coffee, tea, tobacco, red wine, and red grapes. The patients’ main concern
after a successful bleaching treatment remains maintaining the bleached color over a period of
time. In the current study the Sonicare Advance toothbrush was proven more effective than a
manual toothbrush in maintaining the color of bleached teeth for 6 months. This finding, added to
the established record of safety, superior plaque removal, and gingivitis reduction31-33 and extrinsic
stain removal for this device, make Sonicare an excellent choice for patients interested in overall
oral health and specifically tooth whitening maintenance.
168
Table 2—Ranking and Scoring of Vita Classical Shades
Shade
Score
B1–
1
B1
2
A1
3
B2
4
D2
5
A2
6
C1
7
C2
8
D4
9
A3
10
D3
11
B3
12
A3.5
13
B4
14
C3
15
A4
16
C4
17
Lightest
Darkest
169
Table 3—Number of Subjects per Group by Visit
Manual
Sonicare
Screening
22
21
Baseline prebleaching
22
21
Baseline postbleaching
19
21
1 Month
18
19
2 Months
17
19
3 Months
14
18
6 Months
13
18
170
Table 4—Study Demographics (Age)
Statistic
Manual
Sonicare
Minimum
20
21
1st quartile
26
27
Mean
34.0
Median
29
32
3rd quartile
44
46
Maximum
51
66
N
22
21
Missing
1
0
Standard deviation
10.6
36.7
13.3
Table 5—L*a*b* Mean Differences (postbleaching baseline to 6 months)
Difference in Mean (SD)
L*
a*
b*
Manual
Sonicare
Manual
Sonicare
Manual
Sonicare
–3.3 (3.5)
1.5 (2.9)
0.9 (1.5)
0.3 (1.4)
2.3 (2.6)
0.2 (1.6)
Figures
171
Figure 1—CIE L*a*b* Color Space
172
Mean Vita Scores
All Teeth
6
4
5
Fi
3
Mean (All Teeth) Vita Score
7
8
Manual
Sonicare
0
5
10
# Weeks Post-Bleaching
Figure 2—Overall mean Vita scores over time.
173
15
20
25
Mean Vita Scores
Tooth 8
8
5
10
15
20
7
6
5
0
5
10
15
# Weeks Post-Bleaching
# Weeks Post-Bleaching
Mean Vita Scores
Tooth 9
Mean Vita Scores
Tooth 10
25
8
20
0
5
10
15
20
25
4
5
6
7
Manual
Sonicare
3
Mean (Tooth 10) Vita Score
4
5
6
7
Manual
Sonicare
3
Mean (Tooth 9) Vita Score
4
25
8
0
Manual
Sonicare
3
Mean (Tooth 8) Vita Score
4
5
6
7
Manual
Sonicare
3
Mean (Tooth 7) Vita Score
8
Mean Vita Scores
Tooth 7
0
# Weeks Post-Bleaching
5
10
15
# Weeks Post-Bleaching
Figure 3—Mean Vita scores by tooth over time.
(a)
(b)
174
20
25
(c)
Figure 4—Images of a representative subject from the manual toothbrush group (a) at
screening, (b) at post bleaching baseline, (c) at 6 months after the end of bleaching.
175
(a)
(b)
(c)
Figure 5—Images of a representative subject from the Sonicare toothbrush group (a) at
screening, (b) at post bleaching baseline, (c) at 6 months after the end of bleaching.
176
80
Luminance L*
70
60
50
4
C
3
A4
C
5
B4
A3
.
3
B3
D
2
1
4
A3
D
C
C
B2
D
2
A2
B1
A1
40
Vita Classical shades in manufacturer's order
Figure 6—Luminance component of CIE L*a*b* color (middle-middle third of tab) vs
manufacturer’s order for Vita Classical shade tabs.
Acknowledgments
This work was supported by Philips Oral Healthcare, Inc.PRODUCT REFERENCES
Philips Oral Healthcare, Inc, Snoqualmie, WA 98065; (800) 676-SONIC
b
Vita Zahnfabrik, Bad Säckingen, Germany; distributed in the USA by Vident, Brea, CA 92621;
(800) 828-3839
c
Ultradent Products, Inc, South Jordan, UT 84095; (800) 496-8337
d
The Procter & Gamble Company, Cincinnati, OH 45202; (800) 492-7378
e
Adobe Systems, Inc, San Jose, CA 95110; (800) 833-6687
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177
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11. Kugel G, Perry RD, Hoang E, Scherer W. Effective tooth bleaching in 5 days: using a combined
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12. Li Y. Toxicological considerations of tooth bleaching using peroxide-containing agents. J Am
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13. Leonard RH Jr. Efficacy, longevity, side effects, and patient perceptions of nightguard vital
bleaching. Compend Contin Educ Dent. 1998;19:766-774.
14. Haywood VB, Leonard RH, Dickinson GL. Efficacy of six months of nightguard vital bleaching
of tetracycline-stained teeth. J Esthet Dent. 1997;9: 13-19.
15. Haywood VB, Leonard RH, Nelson CF, Brunson WD. Effectiveness, side effects and long-term
status of nightguard vital bleaching. J Am Dent Assoc. 1994;125:1219-1226.
16. Matis BA, Cochran MA, Eckert G, Carlson TJ. The efficacy and safety of a 10% carbamide
peroxide bleaching gel. Quintessence Int. 1998;29:555-563.
17. Haywood VB. Historical development of whiteners: clinical safety and efficacy. Dent Update.
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18. Gegauff AG, Rosenstiel SF, Langhout KJ, Johnston WM. Evaluating tooth color change from
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19. Stanford CM, Srikantha R, Wu CD. Efficacy of the Sonicare® toothbrush fluid dynamic action on
removal of human supragingival plaque. J Clin Dent. 1997;8(1 Spec No):10-14.
20. Stanford CM, Srikantha R, Kirchner HL, Wu CD. Removal of supragingival plaque in an
intraoral model by use of the Sonicare® toothbrush. J Int Acad Periodontol. 2000;2:115-119.
21. Wu-Yuan CD, Anderson RD, McInnes C. Ability of the Sonicare® electronic toothbrush to
generate dynamic fluid activity that removes bacteria. J Clin Dent. 1994;5:89-93.
22. Hope CK, Petrie A, Wilson M. In vitro assessment of the plaque-removing ability of
hydrodynamic shear forces produced beyond the bristles by two electric toothbrushes. J
Periodontol. In press.
23. McInnes C, Johnson B, Emling RC, Yankell SL. Clinical and computer-assisted evaluations of
the stain removal ability of the Sonicare® electronic toothbrush. J Clin Dent. 1994;5:13-18.
24. Zammitti S, Habib C, Kugel G. Use of environmental scanning electron microscopy to evaluate
dental stain removal. J Clin Dent. 1997;8(1 Spec No):20-25.
25. Bass CC. An effective method of personal oral hygiene; part II. J La State Med Soc.
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26. Anderson C, Kugel G. Rebound evaluation of tetracycline stained subjects treated with a 6.5%
hydrogen peroxide gel; quantitative assessment by standard digital photography [abstract]. J Dent
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28. Matis BA, Mousa HN, Cochran MA, Eckert GJ. Clinical evaluation of bleaching agents of
different concentrations. Quintessence Int. 2000;31:303-310.
29. O'Brien WJ, Groh CL, Boenke KM. A new, small-color-difference equation for dental shades. J
Dent Res. 1990;69:1762-1764.
30. Paravina RD, Powers JM, Fay RM. Dental color standards: shade tab arrangement. J Esthet
Restor Dent. 2001;13:254-263.
31. Tritten CB, Armitage GC. Comparison of a sonic and a manual toothbrush for efficacy in
supragingival plaque removal and reduction of gingivitis. J Clin Periodontol. 1996;23:641-648.
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Chapter 10
Intrapulpal Temperatures with Light Activated Whitening
Effects of a Light Activated Bleaching System on Pulp Chamber
Temperature in Vitro
179
ABSTRACT
Several new techniques and materials for in-office bleaching have been introduced recently. The
aim of this in vitro study was to measure the temperature increase in pulp chamber produced by
Zoom light and to investigate the influence of this light in conjunction with the application of
bleaching gel on temperature rise. Ten extracted caries-free, unrestored human maxillary anterior
teeth were used for the study. Each tooth was exposed three times in both groups (n=30 per
group). The root of each tooth was cut about approximately 2-3mm apically to the CEJ and the
apical orifice of the root canal was enlarged. The remaining pulp tissue was removed and the empty
pulp chamber was filled with a heat sink compound which replaced the pulp tissue as a heat
conducting medium. A thin K-type thermocouple was inserted to the pulp chamber through the cut
root area. The root surfaces of the tooth were partially submerged in a water bath during the testing
procedure at 37.5oC . In the first group, whitening gel, 25% hydrogen peroxide was applied to the
buccal surfaces of teeth, approximately 1-2mm thick. Then the light was positioned at ~2.50 inches.
The material was applied according to manfacturers instrutions. In the second group, the same
teeth were exposed with the Zoom light without application of bleaching gel.
The temperature at
the pulp before treatment (baseline) and temperature increase during exposing the light were
measured for both treatment modalities. There was a 5 minutes interval between the end of one
measurement and begining of the next. The mean temperature rise for group I (light and bleaching
gel) was 1.11oC(0.18 ). The mean temperature use for group II (light alone) was 1.01 oC (0.12 ).
There was a statistically significant difference between two groups (p= 0.003). Application of Zoom
light in conjuction with the application of bleaching gel produced greater temperature rise than did
the light alone. The maximum temperature rise was seen in the first 5 minutes of the treatment for
both groups then the temperature decreased.
Although a difference was noticed between the
group receiving light and gel (group I) versus the group receiving light (group II), neither group
showed significant increase in the intrapulpal temperature of teeth when used for the recommended
exposure time.
180
INTRODUCTION
Tooth Whitening has become one of dentistry’s most popular esthetic procedures as it is a
conservative treatment for discolored teeth 1. Power bleaching is an in-office whitening technique
developed to bleach teeth in a single visit. It’s done by the combination of a whitening agent, such
as, peroxide, and an auxiliary, such as light
2, 3
. Currently, the in-office whitening technique uses a
15% to 35% hydrogen peroxide whitening agent (heated or non-heated); the dentist-prescribed
home-applied technique most commonly uses a 10% to 15% carbamide peroxide gel. The
advantage of the in-office procedure is that it does not require patient compliance and results may
be seen immediately. The disadvantage is the chair time, cost to the patient, and the possibility of
multiple visits. A light-activated chairside whitening system has the potential advantages of taking
less time and providing quicker results.
Recently, several new techniques and materials for in-office bleaching have been introduced. The
Zoom Chairside teeth whitening system is one of the power bleaching systems that consists of a
mercury Halide lamp filtered to emit light in the 350-400nm range.
Tooth sensitivity is the most common side effect of whitening4 .Concerns have been raised with the
use of in-office whitening system energy sources like lasers, plasma arc lights and infrared lamps.
It’s believed that these systems activate peroxide formulations and may induce a temperature rise
that could cause sensitivity. Additionally, it has been reported that the light by itself might have a
bleaching effect 2.
Lately, one study article reported the efficacy of the light whitening system whereas another study
publication accomplished the opposite1, 2. In a recent investigation done in our lab employing a
mercury halide light activated bleaching system significant sensitivity was reported. In this study 30
patients received treatment with the light & 25% hydrogen peroxide gel, gel alone or light alone.
181
The gel and light group reported a 90 % severe to moderate tooth sensitivity rate. This was
significantly higher than the other groups. (submitted to IADR, 2004).Therefore the aim of this in
vitro study was to measure the temperature increase in pulp chamber produced by Zoom light and
to investigate the influence of this light in conjunction with the application of bleaching gel on the
temperature rise.
EXPERIMENTAL DESIGN
Ten extracted caries-free, unrestored human maxillary anterior teeth were used for the study.
Teeth were randomized and used for three separate temperature recordings for a total of thirty
readings per group. Two groups were designed Group 1 was treated with bleaching gel and ZOOM
light was applied for three cycles of 20 minutes .Group 2 was treated only with ZOOM light for three
cycles of 20 minutes. Every 5 minutes temperatures were measured for each group using K-type
thermocouple. The mean temperature and p-value for group 1 and group 2 were calculated.
MATERIALS AND METHODS
Ten extracted caries-free, unrestored human maxillary anterior teeth were used for the study. After
the teeth were polished with pure pumice to remove any surface debris or contaminants, they were
stored in distilled water until used. The root of each tooth was cut about 2-3mm apically to the CEJ
and the apical orifice of the root canal was enlarged. The remaining pulp tissue was removed and
the empty pulp chamber was filled with heat sink compound (American Oil and Supply Co., Newark,
NJ, USA) which replaced the pulp tissue as a heat conducting medium. A thin K-type thermocouple
was inserted to the pulp chamber through the cut root area.
The root surfaces of the tooth were partially submerged in a water bath during the testing
procedure. This method effectively stabilized the internal baseline temperature at 37.5°C This also
minimized the effects of ambient temperature changes and provided a consistent initial temperature
182
for each data set. In the first group, whitening gel, 25% hydrogen peroxide was applied to the
buccal surfaces of teeth, approximately 1-2mm thick. Then the light was positioned according to the
manufacturer’s instructions using the integral bite appliance guide to set the distance between the
teeth and the light source approximately 2.50 inches. The teeth were exposed with the Zoom light
for 20 minutes. After each 20minute session the whitening gel was rinsed off, and reapplied. In the
second group, the same teeth were exposed with the Zoom light without application of bleaching
gel. The temperature at the pulp before treatment (baseline) and temperature increase during
exposing the light were used for both treatment modalities. There was a 5 minute interval between
the end of one measurement and the beginning of the next.
RESULTS
The mean temperature rise was 1.11ºC(0.18) in the first group where the light was used with
bleaching gel and 1.01ºC(0.12) in the second group at 5 minutes (graph 1). According to ANOVA
test, there was a statistically significant difference between two groups (p= 0.003). Application of
Zoom light in conjuction with the application of bleaching gel produced greater temperature rise
than did light alone at the 5 minute exposure time. The maximum temperature rise was seen in the
first 5 minutes of the treatment for both groups. Temperature slowly decreased for the 10, 15 and
20 minute recordings (table1).
During the 20 minute exposure time temperatures slowly decreased to 0.43ºC for the light and
0.53ºC for the gel and light system. None of the samples returned to the baseline level during the
20 minute application (table 1).
DISCUSSION
Tooth whitening lights lights may emit heat. The effects of heat on the pulp tissue has been welldocumented. Due to its low compliance nature, lights may cause a temperature increase within the
pulp chamber that may harm the pulp and/or cause tooth sensitivity 5. Zach and Cohen found that a
183
temperature rise of 5,5 C in a healthy pulp resulted in necrosis in 15% of the Macaca rhesus
monkey teeth 6. However in our study the maximum temperature rise was 1,01. Therefore the zoom
light was found to cause only a slight increase in the temperature. However temperature was
increaed when the light was used in conjunction with the 25% hydroge peroxide bleaching agent.
Since these results were obtained in vitro, long-term clinical trials are needed to fully understand
the reasons of hyersensitivity and performance of this new whitening sytem.
SUMMARY
This study concluded the mean temperature rise was 1.11°C for the gel & light when samples are
maintained at body temperature ( table 1). Recently an article published by Hein
4
showed that in
vivo gel temperature change, Zoom! Light bleach gel reached 5°C on the tooth surface during its 20
minute exposure time. The Zoom! Light was designed specifically for tooth bleaching. The results
achieved by this study indicate that although previous reports showed significant temperature rise
on the tooth surface our results demonstrate that the intrapulpal temperature increases only slightly
during the exposure time. Therefore the Zoom light was found to cause only a slight increase in
intrapulpal temperature. The use of the light and gel demonstrated a significantly higher
temperature increase than the light alone. However, this increase is still lower than the necessary to
cause pulpal damage (5.5 °C). The sensitivity noted during light activated bleaching is most
probably increase dehydration on the surface of the tooth. This may relate to 5°C surface
temperature change previously reported on the enamel surface.
Since these results were obtained in vitro, long-term clinical trials are needed to fully understand
the reasons of hypersensitivity and performance of these new whitening systems. The effects of
light activated bleaching systems on temperature rise in the pulp are not clinically significant.
Hanning and Bott have shown that temperatures exceeding 42.5 °C can result in irreversible
damage to pulp tissue 7. The distance between the light and tooth could affect the temperature rise
in the pulp chamber. It is interesting to comment that normally hot liquids are consumed with short
184
term temperatures at 60 °C to 70° C. It’s believed that the pulp only increases a few degrees due to
the thermal insulting properties of the dental hard tissue, when using a regular halogen curing light
7
.Our study would indicate no long term pulpal damage from this light activated bleaching system.
Graph 1:
Zoom Light
Zoom Light + Bleaching Gel
1.2
Mean Temperature Rise
1
0.8
0.6
0.4
0.2
0
0
5
10
15
20
Time of Exposure
Table 1:
Mean Temperature Rise
Time in Minutes
Zoom Light
Zoom Light + Bleaching Gel
Baseline
0 OC(37.5ºC)
0 OC(37.5ºC)
5
1.01OC
1.11 OC
10
0.82 OC
0.98 OC
185
15
0.60 OC
0.77 OC
20
0.43 OC
0.53 OC
REFERENCES:
1. Papathanasiou A, Bardwell D, Kugel G. A clinical study evaluating a new chairside and takehome whitening system. Compendium 2001; 22: 289-297.
2. Tavares M, Stultz J, Newman M, Smith V, Kent R, Carpino E, Goodson JM. Light augments
tooth whitening with peroxide. JADA 2003; 134: 167-175.
3. Nathanson D. Vital tooth bleaching: sensitivity and pulpal considerations. JADA 1997; 128:
suppl: 41S-44S.
186
4. Hein DK. Ploeger BJ. Hartup JK. Wagstaff RS. Palmer TM. Hansen LD. In-office vital tooth
bleaching--what do lights add?. Compend of Contin Educ Dent. 2003 Apr; 24(4A):340-52.
5. Blankenau R, Goldstein R, Haywood VB. The current status of vital tooth whitening techniques.
Compendium 1999; 20: 781-794.
6. Zach L, Cohen G. Pulp response to externally applied heat. Oral Surg Oral Med Oral Pathol
1965; 19: 515-530.
7. Hannig M, Bott B. In-vitro pulp chamber temperature rise during composite resin polymerization
with various light-curing sources. Dent Mater. 1999 Jul;15(4):275-81
Chapter 11
Effect of Tooth Whitening on Enamel
An exploratory study using SEM to evaluate the enamel surface effects in
vivo of a 6% hydrogen peroxide strip bleaching system with that of a 2.5%
chlorite tray bleaching system
187
INTRODUCTION
Tooth whitening has become both common and popular, and use of peroxide is now generally
recognized as a safe and effective method for tooth whitening
1-3
. There are a variety of indications
for bleaching single or multiple teeth, including staining from chromagenic foods or other sources,
dental fluorosis, tetracycline staining and devital discolored teeth
4-6
. Concentrations of up to 35%
peroxide are used alone or in combination with various agents for tooth bleaching. Delivery is via
in-office, at-home regimens or combination regimens with or without professional supervision
7, 8
.
Of these, bleaching is most commonly accomplished at-home over a period of a few weeks 9.
Treatment duration may vary based on the degree of staining, since whitening is reported to be a
product of peroxide concentration and contact time
10
. For some difficult stains like tetracycline,
daily bleaching for periods of up to 6 months may be indicated 11.
Efficacy may be established through first or second person observation or various technical
methods. Clinical trials most commonly include use of a shade guide, colorimeter, or computer
digitization to measure color change over time. Of these, methods that assess three-direction
(dimension) color space are reported to be more objective and linear, and as such, may be
preferred for clinical trials research 12,13.
A comprehensive literature review found tooth bleaching agents to be remarkably well-tolerated.
The principal adverse events — tooth sensitivity to temperature changes and local oral mucosal
irritation — were generally mild and transient. Patients with pre-existing sensitivity may be at
highest risk for after-bleaching sensitivity. Several factors are reported to contribute to hard and
soft tissue events, including tray design, formulation, and others 10.
Tolerability may be impacted by poor compliance, overuse, unnecessary product ingestion, and
others 5,. Many of these factors may be associated with the delivery trays (either custom or stock)
which are commonly used in most at-home regimens. Rapid innovation, especially with the advent
of new in-office options for immediate care and the emerging popularity of the direct-to-consumer
188
systems, challenges many of the basic tray-based precepts of the previous decade. One of the
most prominent of these is the whitening strip (Crest, Blend-a-Med or AZ Whitestrips), a
novel system that uses a flexible polyethylene strip to deliver a hydrogen peroxide bleaching gel to
the anterior dentition. These whitening strips are reported to offer specific advantages vs the more
conventional custom tray-based systems, with respect to total peroxide dose, contact time, and
ease of use. Evidence of safe and effective use has been established in clinical and pre-clinical
studies comparing whitening strips to various negative and positive controls. The application of
such bleaching agents to whiten vital-teeth is less well-characterized with little research published
in the scientific literature.
There have been a number of studies evaluating the effect of bleaching on the hardness and
morphology of enamel. The results from these studies have varied. One study concluded that the
use of bleaching agents resulted in a significant reduction in Calcium/Phosphate ratio in enamel
14
and they concluded that bleaching materials may adversely affect the dental hard tissue. Other
authors state that surface hardness and tooth morphology are not deleteriously affected by
bleaching 15.
This clinical trial evaluated the safety of a recently introduced 2.5% sodium chlorite tray-based
whitening system, Odol-med 3 Beauty Kurr, versus a currently marketed 6% hydrogen peroxide
strip system. Sodium chlorite is the only chlorite salt produced commercially in significant quantities.
It is used mainly for the generation of chlorine dioxide in situ for bleaching textiles, in pulp and
paper processing, and for disinfection. Scanning Electron Micrographs from replicas were used to
observe surface effects/ morphological changes in teeth enamel after treatment with bleaching
agents. The observations included any changes in the porosity, precipitations, erosive process,
destruction and depression areas, with the formation of craters and exposure of enamel rods.
189
OBJECTIVE
The aim of this exploratory study was to assess any surface morphological changes in tooth
enamel after treating with a currently marketed hydrogen peroxide strip bleaching system and a
currently marketed sodium chlorite tray-based system using an SEM Investigation.
MATERIAL AND METHODS
This was a parallel, examiner-blind, single-center study. Approximately 10 generally healthy
subjects (5 per treatment group) were randomly selected from a pool of subjects undergoing a 3
week regimen of vital tooth bleaching with either a 6% whitening strip (Group I) or 2.5% sodium
chlorite tray system (Group II). The Test Products were:

AZ Whitestrips (Polyethylene strips containing 6% Hydrogen Peroxide gel).
Manufactured by The Procter & Gamble Company.

Odol-med 3 Beauty Kur (Tooth Whitening System including the Activator containing 2.5%
Sodium Chlorite). Manufactured by Glaxo Smithkline.
Subjects assigned to Crest Whitestrips treated their anterior maxillary tooth surfaces for a period of
three weeks. The product was used twice a day for 30 minutes each. Subjects assigned to Odolmed 3 also treated their maxillary surfaces for three-week duration, as per the manufacturer’s
instructions. This product was used twice a day for 10 minutes. The first product use was
supervised at the Product Distribution visit. All other uses were completed at home and were
unsupervised.
Subjects on the Group I brushed twice daily with AZ Protezione Caries toothpaste (currently
marketed cavity protection toothpaste). It contains 0.32% Sodium Fluoride (Procter & Gamble
Company). Subjects on the Group II had whitening toothpaste provided to them with their test
product. All subjects were assigned an Oral B40 Soft Bristle toothbrush (Braun Oral B Company).
Inclusion Criteria
190
The subjects were included if they:
1. provided written informed consent prior to their participation and be given a copy of the signed
consent form,
2. were at least 18 years of age at the time of enrolment,
3. had a minimum of 16 natural teeth, specifically all 4 maxillary anterior central and lateral
incisors.
4. agreed to return for the scheduled visits and follow the study procedures,
5. agreed not to participate in any other oral /dental product clinical studies during the course of
this study,
6. agreed to refrain from the use of any non-study dentifrices and tooth whitening products for the
study duration and
7. had teeth sufficiently free of caries
Exclusion Criteria
The subjects were excluded from the 2003088 study if they:
1.
had restorations or dental crowns, generalized gingival recession or clinically meaningful
malocclusion involving the maxillary or mandibular anterior dentition,
2. presented with any pre-existing oral or medical condition that the examiner or investigator
determines may place the subject at increased health risk from study participation,
3.
4.
had any dental care planned during the duration of the study that may:

impact the general health of the subject

impact the ability of the subject to bleach teeth according to the protocol

require a dental prophylaxis

involve the anterior dentition
were undergoing current treatment for gingivitis, periodontitis, or caries,
191
5.
reported having teeth previously bleached by a professional treatment, over-the-counter
bleaching kit, or clinical trial test product,
6.
were currently using a chlorhexidine mouth rinse or Listerine mouth rinse,
7.
had teeth with clinically meaningful intrinsic staining due to tetracycline, fluorosis or
hypocalcification,
8.
had self-reported dentinal sensitivity, or
9.
had teeth that cannot be imaged.
Continuance Criteria
Subjects were discontinued for the following reasons:
1. use of dentifrices or mouthrinses or tooth whitening products other than those assigned;
2. elective dentistry prior to study completion, including dental prophylaxis;
3. Inability or unwillingness to comply with study procedures including test product regimen.
The same continuance criteria were governing the subject’s eligibility to continue participation in
this study.
An SEM Investigation was done on Baseline, Day 14 and Day 21. Subjects discontinued product
use at the Day 21 visit. During the entire study period subjects brush with their assigned toothbrush
and toothpaste. An impression of the dentition and SEM investigation was conducted and used as
the post treatment assessment. A rubber impression of both the maxillary and the mandibular
anterior teeth was taken for each of the selected subject. These were done both at the baseline
(pre-treatment) and after completing the product usage (post treatment).
The impressions were poured with epoxy resin material. The buccal surfaces of the two upper
central incisors were evaluated. The buccal surfaces of central incisors were gold sputtered and
then mounted in metallic stubs. All the study material was labeled with the subject number, tooth
number and the evaluation day.
192
Observations under the SEM were made on changes in porosity, precipitations, erosive process,
destruction and depression areas, with the formation of craters and exposure of enamel rods.
Photographs of the scans were taken. Two different evaluators who were blinded to the test product
did the observations and scoring. The scoring was done independent of one another.
The scoring was done at constant magnifications (x500, x2000 and x5000). Four readings were
made on each tooth, dividing the surface into four quadrants (figure 1). The reading was performed
in the centre of each quadrant. All the scores were collected and evaluated according with the
scores (figure 2) and the location. The SEM scores were done by two independent graders using a
scoring system of 0-4.
Due to small sample size, non-parametric methods were used to explore the data (figures 3-6). In
addition to the visual observation models were poured in epoxy die and 3D laser profilometry was
done on all samples. Delta Ra data was obtained and statistical differences from baseline were
determined.
RESULTS
Scores from the visual evaluation of the SEM data indicated that there was little evidence of any
increased surface roughness in either group following treatment (Table 1). This is based on the
visual evaluation of two independent calibrated evaluators.
Evaluations were based on a
comparison between baseline (no treatment) and after 21 days of exposure. It should be noted that
all evaluations indicated that the roughness noted was superficial with no deep roughness
observed.
193
The profilometry data (table 2) shows a good biological diversity with both products producing a
similar but insignificant change in surface roughness. Differences between groups showed no
statistical significance using a nonparametric analysis, the Wilson rank sum test. This produces a
P-value =0.69 which indicates that neither treatment had any adverse effects on the surface
morphology the teeth examined. These results confirm the data presented in table 1.
DISCUSSION
This study represents the first paper to evaluate enamel following tooth whitening using both visual
analysis and laser profilometry. There have been other studies to evaluate the hard tissue effects of
tooth whitening. These have employed microhardness and SEM analysis of the enamel surfaces
14,
15
. In this study the use of a visual scoring system for changes on enamel morphology indicated that
there were no significant changes from the baseline in either the 6% Hydrogen Peroxide gel group
or the 2.5% Sodium Chlorite group. It is important to note that in all evaluations the roughness
observed was superficial in nature and that all teeth varied slightly at baseline. This is expected
given the variability of enamel clinically and these observations are only relevant when compared
within the sample.
In order to confirm our SEM visual evaluation Laser profilometry was done for both groups.
Measurements were compared using baseline (before treatment) and following 21 days of
exposure. Samples were analyzed for differences from baseline for both the 6% hydrogen peroxide
and the 2.5% Sodium Chlorite groups. There is no statistical difference between the baseline and
21 day samples. This is true for both tooth whitening systems. In both groups the 21 day dosing
has no effect on surface roughness of the exposed teeth. In conclusion this study indicates that 21
day exposure to two different tooth whitening systems had no observable or measurable adverse
effects on enamel.
Tables and figures:
194
Figure 1
Four readings were made on each tooth, dividing the surface into four quadrants
Figure 2:
Scoring scales for SEM evaluation
Figure 3:
Samples of SEM 2,000X with roughness score 0
Figure 4:
Samples of SEM 2,000X with roughness score 1
Figure 5:
Samples of SEM 2,000X with roughness score 2
Figure 6:
Samples of SEM 2,000X with roughness score 3
Table 1:
Average scores per group by quadrant
Table 2:
Laser profilometry Ra analysis
Figure 1:
A
B
C
D
Figure 2:
SEM Scores
Score 0
no visible surface roughness
Score 1
5-25% of the surface displays roughness
Score 2
25-50% of the surface displays roughness
Score 3
50-75% of the surface displays roughness
Score 4
75-100% of the surface displays roughness
195
Figure 3:
Figure 4:
196
Figure 5:
Figure 6:
197
Table 1:
Quadrant A
Average per Group
500X
GROUP I
GROUP II
2000X
Baseline
14-Day
21-Day
Baseline
14-Day
21-Day
0
0.4
0.2
1.4
1.6
0.8
0
0
0.2
1.6
1.6
0.4
198
Quadrant B
Average per Group
500X
GROUP I
GROUP II
2000X
Baseline
14-Day
21-Day
Baseline
14-Day
21-Day
0.2
0.4
0
1.6
1.8
1
0.2
0.2
0
1.6
1.6
0.6
Quadrant C
Average per Group
500X
GROUP I
GROUP II
2000X
Baseline
14-Day
21-Day
Baseline
14-Day
21-Day
0.4
0.4
0
2
1.8
0.6
0.4
0.6
0
2
1.4
0.6
Quadrant D
Average per Group
500X
GROUP I
GROUP II
2000X
Baseline
14-Day
21-Day
Baseline
14-Day
21-Day
0.8
0.4
0
2.2
1.6
0.6
0.6
0.2
0
1.2
1.6
0.6
199
Table 2:
Specimen Treatment
5
Group I
12
Group I
20
Group I
24
Group I
32
Group I
Baseline
0.5192
0.2458
0.1815
0.2189
0.3545
0.30398
21 day
0.7154
0.3715
0.2208
0.2034
0.2613
0.35448
Delta Ra
0.1962
0.1257
0.0393
-0.0155
-0.0932
0.0505
Specimen Treatment
1
Group II
3
Group II
4
Group II
25
Group II
27
Group II
Baseline
0.1305
0.2588
0.2792
0.3158
0.3365
0.26416
21 day
0.1976
0.2505
0.2748
0.3244
0.3
0.26946
Delta Ra
0.0671
-0.0083
-0.0044
0.0086
-0.0365
0.0053
Mean Value
Mean Value
REFERENCE
1. Haywood VB, Heymann HO. Nightguard vital bleaching. Quintessence Int 1989;20: 173-6.
2. Goldstein RE. In-office bleaching: where we came from, where we are today. J Am Dent Assoc
1997; 128: 11S – 15S
3. Burrell KH. ADA supports vital tooth bleaching – but look for the seal. J Am Dent Assoc 1997
128:3S-5S.
4. Croll TP, Sasa IS. Carbamide peroxide bleaching of teeth with dentinogenisis imperfecta
discoloration: report of a case. Quintessence Int 1995; 26:683-6
5. Frazier KB. Nightguard bleaching to lighten a restored, nonvital discolored tooth. Compend
Contin Educ Dent 1998; 19:810-3
6. Small BW. The application and integration of at-home bleaching into private dental practice.
Compend Contin Educ Dent 1998;19:799-806
200
7. Kugel G, Perry RD, Hoang E, Scherer W. Effective tooth bleaching in 5 days: using a combined
in-office and at-home bleaching system. Comp Contin Educ Dent 1997; 18:378-83.
8. Li Y. Toxicological considerations of tooth bleaching using peroxide-containing agents. J Am
Dent Assoc 1997; 128:31S-36S
9. Leonard RH.
Efficacy, longevity, side effects, and patient perceptions of nightguard vital
bleaching. Compend Contin Educ Dent 1998; 19: 177-780
10. Haywood VB, Leonard RH, Dickinson GL. Efficacy of six months of nightguard vital bleaching
of tetracycline-stained teeth. J Esthet Dent 1997;9: 13-9
11. Haywood VB, Leonrd RH, Nelson CF, Brunson WD. Effectiveness, side effects, and long-term
status of nightguard vital bleaching. J Am Dent Assoc 1994; 125 1219-26
12. Gegauff AG, Rosenstiel SF, Langout KJ, Johnston WM. Evaluation of tooth color change from
carbamide peroxide gel. J Am Dent Assoc 1993;124:65-72.
13. Rotstein I. Dankner E. Goldman A. Heling I. Stabholz A. Zalkind M. Histochemical analysis of
dental hard tissues following bleaching. Journal of Endodontics. 22(1):23-5, 1996 Jan.
14. White DJ. Kozak KM. Zoladz JR. Duschner HJ. Gotz H. Effects of Crest Whitestrips bleaching
on surface morphology and fracture susceptibility of teeth in vitro. Journal of Clinical Dentistry.
14(4):82-7, 2003.
15. Spalding M. Taveira LA. de Assis GF. Scanning electron microscopy study of dental enamel
surface exposed to 35% hydrogen peroxide: alone, with saliva, and with 10% carbamide
peroxide. Journal of Esthetic & Restorative Dentistry: Official Publication of the American
Academy of Esthetic Dentistry. 15(3):154-64; discussion 165, 2003.
Summary and Discussion
In Chapter 1, as an introduction to the main topic of this study, a major aspect of modern dentistry
was presented. The area of tooth whitening, although one of the fastest growing and affecting
millions of patients, it relies on a weak base of scientific evidence. The actual mechanism of action
of hydrogen peroxide on enamel and dentin is presumed to be an oxidation process that affects
both enamel and dentin. The assumption is that because the radicals have unpaired electrons, they
are extremely electrophylic and unstable and will attack most other organic molecules to achieve
stability, generating other radicals. These radicals can react with most unsaturated bonds, resulting
in disruption of electron conjugation and a change in the absorption energy of the organic
201
molecules in tooth enamel. Simpler molecules that reflect less light are formed, creating a
successful whitening action. This process occurs when the oxidizing agent (hydrogen peroxide)
reacts with organic material in the spaces between the inorganic salts in tooth enamel. This
assumption is difficult to prove. Our data supports the idea that there must be significant
penetration of the peroxide into dentin and that once it reaches the dentin it is in a form that is able
to oxidize the organic material causing a lightening effect. The early work on tetracycline staining
supports the idea that there is a penetration of the free radical. These studies relied on small
sample sizes and incorporated high dose delivery systems. The causes of both intrinsic and
extrinsic staining were reviewed following the section on penetration of hydrogen peroxide. This
was done to support the belief that these intrinsic stains require significant penetration in order for
these to be lightened.
It is interesting that so little is known about the concentration and dose response during the
whitening process. The assumption has been that the higher the concentration the better the effect.
It has also been assumed that a dose of 30-50 mg was required to whiten teeth. We examine in this
thesis the use of a novel low dose delivery system using 9-11 mg of carbamide peroxide on a
polyethylene strip.
A review of the evolution of tooth whitening demonstrates the field is not new. The review of the
literature also shows that there a number of systems available for tooth whitening. The most
common bring the night guard vital bleaching method. Other systems have been more recently
introduced such as the polyethylene strip and paint-on products. The area of light activated
bleaching as indicated in the introduction remains one of the most controversial areas in this field.
This is due to the poor quality of many of these studies the results have been questioned. The
mechanism of action of these light (and heat) activated systems is addressed along with the
evidence that the assumed increased breakdown of the hydrogen peroxide and thus increased
efficacy would require temperatures the would be detrimental to vital teeth.
202
Finally; the issue of adverse events and possible side effects were reviewed. The toxicological side
effects seem to be minimal however tooth sensitivity can be quite significant. Studies have shown
that sensitivity occurs in 55 to 75% of the treatment groups. The placebo groups also experienced
20-30% sensitivity. The causes of tooth sensitivity are poorly understood. It is most often seen as
the result of tooth dehydration.
In Chapter 2 a randomized, single-center, double-blind, parallel-group, placebo controlled trial
evaluating the whitening efficacy and safety of 2-week, twice daily use of a 5.3% hydrogen
peroxide tooth-bleaching gel delivered on polyethylene film. This system employed a low dose
delivery of 9-11 mg of carbamide peroxide gel. Efficacy was based on change in Vita® shade
scores from baseline to the end of treatment. Baseline Vita® shade scores were similar for the two
treatment groups. Scores were 8.18 (D-4 to A-3) and 8.28 (D-4 to A-3), and, on average, ranged
from A-2 to C-4 and from A-2 to A-4 in the active and placebo groups, respectively. Sixty-four
percent of teeth treated in the active group started at scores of C-2 or whiter. Thirty-three patients in
each group completed treatment. Use of the peroxide-containing gel led to a mean change in
baseline Vita® shade score of –3.70 ± 0.35, compared with a change of –0.87± 0.24 after use of a
placebo gel. After adjustment for baseline scores, the mean difference in shade change between
the peroxide gel–treated group and placebo-treated group was –2.85 ± 0.41 (P < 0.0001). Both
treatments were generally well tolerated. Adverse effects after treatment were minimal and were
observed in less than 10% of subjects in either treatment group. The main findings in these
participants were papillary swelling, minor cervical inflammation, and a superficial cervical lesion.
This was the first study to examine the use of such a thin film of hydrogen peroxide gel in tooth
whitening. Prior to the research dentist would us a night guard fabricated to a stone model of the
patient and contoured at the margins Spacer was routinely used on the facings of the teeth to
insure that a high dose of material could be delivered to the teeth with the assumption that this was
necessary to have a significant amount of material in contact with the teeth for tooth whitening to
203
occur. This study was the first to demonstrate that a low dose (9-11 mgs) but higher concentration
5.3 % hydrogen peroxide applied for 30 minutes twice daily resulted in significant lightening when
compared to placebo control. This study was controversial since this delivery system was easy to
apply, effective, minimal adverse events and did not require the fabrication of a tray and therefore
had the potential to be used as over-the-counter product.
In Chapter 3 the question of concentration response using a low dose (4-11 mg) delivery system
was addressed employing digital image analysis of treatment groups in order to analyze the
CIELAB tooth color values for b* (yellow – blue), L* (lightness), and a* (red – green).17 Change
values were calculated for any given post-baseline visit. The objective of this study was to
evaluate the peroxide concentration whitening response following self-directed use of whitening
strips over a 28-day period.
A randomized, double-blind, parallel group clinical study was conducted. Thirty-seven healthy adult
volunteers were randomly assigned to one of three groups based on tooth color at screening –
1.8% hydrogen peroxide strips (HPS), 3.3% HPS or 5.3% HPS. Subjects applied the assigned
maxillary strips twice per day for 30 minutes over 28 days. Tooth color was evaluated at day 7, 14 &
28 from digital images of the maxillary 6 anterior teeth using a standard method. Treatments were
compared using analysis of covariance (adjusting for baseline), or analysis of variance at a 0.05
level of significance.
The results of this study demonstrated hydrogen peroxide at concentrations ranging from 1.85.3% resulted in significant (p < 0.05) color improvement versus baseline as early as Day 7. There
was a clear concentration-response for all color parameters (b*, L* and E*) at all time points,
favoring the higher concentrations. While the concentration-whitening relationship approached a
linear response at Day 7, continued treatment resulted in incremental color improvement. All three
204
peroxide concentrations were well tolerated, and no subjects discontinued early due to a treatmentrelated adverse event.
The research provides clear evidence of a peroxide concentration whitening response. Whitening
efficacy was greatest for the highest concentration group (5.3% hydrogen peroxide), while the
intermediate concentration group had an intermediate response. Not surprisingly, this effect most
approached linearity at the earliest time point (Day 7). At that time, adjusted mean b* for was –
1.43, –0.84, and –0.44 in the higher, intermediate and lower concentration groups, respectively.
Relative to the lowest concentration strip, this represented a 225% improvement in whitening for the
5.3% strip (a 194% increase in concentration), and a 91% improvement in whitening for the 3.3%
strip (a 83% increase in concentration).
Despite the concentration differences (there was nearly a three-fold difference between the lowest
and highest concentration tested in this research), all three strips tested in this research carried a
low total amount of peroxide. The total amount of hydrogen peroxide on each pre-dispensed strip
ranged only from 3.6-10.6 mg. Relative to some tray-based systems, which may deliver up to 2
grams of bleaching gel, total peroxide delivered with any of these strips was remarkably low. This
likely contributed to the low overall adverse event rate seen in this trial.
This new clinical research provides evidence of a concentration gradient for whitening response
following use of a low peroxide dose strip whitening system. As such, this may represent a first
example of concentration ranging for one of the self-directed bleaching systems. More importantly,
the research also provides evidence of the sensitivity and robustness of the measurement method
– in this instance – digital imaging.
The study in Chapter 3 compliments the earlier work done in Chapter 2. In Chapter 2 we discussed
the introduction of a low dose novel delivery system and we demonstrate its effectiveness vs contro
205
using a value-ordered shade guide. In Chapter 3 we determine that there is a concentration
response when measured digitally using this low dose system.
This research adequately differentiated multiple concentrations from low to high over time. With
b* as an endpoint, the study demonstrated a nearly linear concentration response relationship,
with measured efficacy differences at Day 7 that reasonably modeled the real concentration
differences between groups. As such, the research provides important evidence of the validity of
this method and endpoint for practice-relevant evaluation of vital bleaching technologies.
In Chapter 4 we evaluated the effectiveness of light-curing (heat conversion) vs. no light-
curing (no heat conversion) of a 35% hydrogen peroxide in-office tooth whitening system.
Heat conversion is used as a means of speeding up the breakdown and thus increasing the
efficacy of the hydrogen peroxide oxidation process. This was one of the first controlled
studies to evaluate light activated bleaching.
Twenty patients with sound medical history (without tooth sensitivity) participated in this
randomized, parallel clinical evaluation. Only six maxillary anterior teeth with discoloration and a
tooth shade of A3 or darker were selected. Patients received a complete prophylaxis and were
evaluated for initial (baseline) shade by three independent evaluators, precalibrated at 85% rater
reliability in determining shades before the experiment began. Participants received a 20-minute
chairside whitening treatment with a 35% hydrogen peroxide agent using a reflective resin barrier
for gingival isolation. During the whitening treatment, the 35% hydrogen peroxide agent was light
activated with a halogen curing light on teeth Nos. 6 through 8 (Group I), but was not light-activated
on teeth Nos. 9 through 11 (Group II). All patients returned 24 hours after the whitening application
for shade evaluation. Although there were isolated instances (7 out of 20 patients) of greater
degrees of lightening in the light-curing group, there was no statistically significant difference using
206
the Mann-Whitney U test (P > .05). This study indicates that light-curing is optional with this 35%
tooth whitening system.
Of the 20 patients in this study, 7 patients experienced an increase in lightening of the split arch
protocol with an average lightened increase of 1.714 shades as compared to the non–light-cured
side. This was not a significant clinical change. Any shade difference as noted by the light-activated
side was most likely a result of dehydration resulting from heat generated by the halogen curing
light. Statistically, there was no significant difference between the light-activated side when
compared to non–light-activated side.
The results contradict other studies, which have indicated that light activation causes an
increased whitening effect as used with hydrogen peroxide whitening agents
The study in Chapter 5 is complimentary to that in Chapter 4. The purpose of this study
was to compare the efficacy of color changes of two in-office tooth whitening systems, a
15% Hydrogen peroxide light activated system and a 38% non-light activated hydrogen
peroxide system.
In this split-arch, randomized, parallel, blinded clinical evaluation six maxillary anterior teeth
(N=60) A-2 or darker were selected using the value order Vita Shade Guide. Patients
received one-hour light-activated chair side treatment using 15% H2O2 teeth 6-8 (Group I),
teeth 9-11 received a 38% H2O2 system for 1 hr without a light (Group II). Before and after
treatment images were taken. L*, a* and b* and Vita shades were measured. The Olympus
C2500L high resolution digital camera is utilized for sampling. To ensure proper color
analysis an extended procedure of sampling nine locations on the central incisor, lateral
incisors of the maxillary and mandibular arches was completed. This data is then averaged
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to find a mean color and standard deviation of color on each tooth. A Gaussian blur filter
was applied during post processing which does an averaging of color over the digitally
sampled photo. All digital images were then analyzed to yield L*, a* and b* data Patients
returned after 2 weeks for final shade evaluation.
The L*, a* and b* data indicates that both BriteSmile and Opalescence Xtra Boost whitened teeth to
statistically significant level (P=.01) for L* 3.6 (BriteSmile), 3.8 (Xtra Boost) and b* -6.0 (BriteSmile),
-5.0 (Xtra Boost) equivalent to between 3 and 6 shades as determined on a Vita shade guide. The
two whitening systems were not statistically significantly different from pre-bleaching to two weeks
post-bleaching. The Vita Shade Guide results showed that both in-office tooth whitening systems
were effective. Group I averaged 5.9 ± 2.5 and Group II 3.97 ± 2.33 shade changes immediately
after treatment. At the 2-week recall, Group I scored an average of 4.6 ± 2.14 and Group II 4.6 7±
2.3 shade changes, compared to the pre-bleaching shades. A paired sample t-test revealed
statistically significant difference (p<0.0001) between Groups I and II immediately after bleaching,
with Group I performing better. At the 2-week recall, however, only Group I showed a significant
rebound (p=0.0002). At the completion of the study, there was no significant difference between
Groups I and II (p=0.7826).
The clinical observation using a value ordered Vita Shade Guide was confirmed using digital
analysis of L*, a*, b* color values
15
. In addition the digital camera was calibrated for each image.
Unlike other studies, the teeth of the one side were kept moist during bleaching, thus minimizing the
effect of dehydration that can occur while the other lateral side was being bleached. This might
explain why our data does not show the dramatic results reported in another paper. It is reasonable
to conclude that with the increase in temperature, dehydration did occur, which was subsequently
followed by rehydration. Therefore, in spite of the initial perception that an increase in whitening
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took place, the 2-week post-operative evaluation did not demonstrate a difference, which was
confirmed by an absence of a statistically significant difference between the two materials.
This data is particularly relevant since the use of light activated bleaching has been gaining in
popularity in the US. This is partially due to the fact that there are few well controlled, independent
studies in the field. In a study that we just completed at our University but the (data yet
unpublished) we used a metal halide (Zoom) light N=30 patients and we once again found no value
to use of a light in bleaching.
In Chapter 6 we address the issue of hydrogen peroxide penetration as well as mechanism of
action by examining the efficacy of a low dose delivery system on bleaching tetracycline-stained
teeth. We incorporate a patient population with documented intrinsic staining so that we could
evaluate the ability of the low dose gel to penetrate to the dentin. This clinical article reviews the
efficacy of a new 6.5% hydrogen peroxide tooth-whitening gel strip for bleaching teeth that have
been intrinsically stained from tetracycline. Given the severity of the staining in the cases presented
during this conducted clinical trial, the resulting efficacy is dramatic.
A randomized clinical trial compared the efficacy of two at-home vital bleaching systems on
tetracycline-stained teeth. Daily bleaching was conducted over two months. Eligibility was limited to
healthy adult volunteers who had 16 or more natural teeth, including at least 3 gradable maxillary
incisors with significant tetracycline staining. Individuals demonstrating tooth sensitivity or an
immediate need for dental treatment were excluded from participation in this trial.
The 40 randomized subjects included 30 assigned to the strip group and 10 assigned to the tray
group. The study population ranged from 22 to 70 years of age. Approximately half of the sample
presented with moderate to severe tetracycline staining (levels II through IV), one third of whom
had the more severe banding that is occasionally reported following childhood antibiotic use. While
tobacco use was uncommon (15% of the sample), 95% of the study participants consumed coffee,
209
tea, or cola beverages daily. Treatment groups were generally well balanced with respect to
demographic and behavioral parameters and tetracycline stain levels. Efficacy was assessed using
a standard 16-step value-oriented tooth shade guidec used in dentistry to match artificial crowns to
the natural dentition. Shade assessments were performed in a neutral-colored dental operatory
under color-balanced lighting conditions by a trained and calibrated examiner. Tolerability was
assessed by intraoral examination and subject report at each study visit.
Individual shade scores were determined by ordering the 16 shades arranged from dark to light
according to the rank ordering suggested by the manufacturer. To account for unusually dark colors
(often seen with tetracycline stain) or white colors (often seen post-bleaching), this 16-step guide
was supplemented by 2 additional values (C4+ and B1-) representing shades darker than C4 or
lighter than B1. Effectiveness was determined by calculating the change in shade scores from
baseline at each post-treatment visit. Using this method, a decrease in numeric shade score
represented an increase in tooth whiteness. Treatment groups were compared using analysis of
covariance with the baseline shade as the covariant. Comparisons to baseline were 1-sided, while
between-group comparisons were 2-sided using a 5% significance level.
Both treatments were effective overall in improving the shade of tetracycline-stained teeth. Relative
to baseline, the 2 groups averaged approximately 4 to 6.5 units of shade improvement after 2
months of treatment. Observed changes were greater on average after 2 months as compared to 1
month. Response was faster in the strip group. During the first month’s treatment, individuals in the
strip group averaged greater than a 4-unit reduction in tooth shade, which represented a highly
statistically significant (P < .0001) improvement vs. baseline. In contrast, subjects in the tray group
averaged less than a 1-shade reduction during the first month, not differing statistically from
baseline (P > .10). Adjusting for baseline, the strip group averaged 2.6 to 3.2 units more shade
reduction compared with the tray group control. With respect to between-group comparisons, the
strip group experienced statistically significantly superior reductions (P < .01) in shade compared
with the tray group at both the 1- and 2-month time points.
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This study confirms early observations of the need for extended contact time in many tetracyclinestained patients. After 2 months of daily treatment, involving approximately 60 hours of strip use or
120 hours of tray use, no subjects had yet reached the predetermined bleaching cutoff (B1-). In
these subjects, additional time may be necessary to affect maximum color change. Previous reports
suggest a minimum of 2 months of treatment, hence the time point elected in this study.
This data demonstrates the difficulty, regardless of the delivery system, in bleaching tetracyclinestained teeth. This confirms that the peroxide does penetrate to the dentin and that the oxidation
process affects the color of the stained dentin. It also confirms that this is a slow process and
requires extended exposure.
Chapter 7 is the continuation of the 2 month study described in Chapter 6. Chapter 6 was the
published data from the first 2 month of this 6 month study. A variety of indications exist for
bleaching single or multiple teeth, including tetracycline staining. The primary objective of this study
was to evaluate clinical response following extended daily use of a trayless 6.5% hydrogen
peroxide tooth bleaching gel on tetracycline stain. In this research, 10% carbamide peroxide in an
at-home daytime tray delivery system was used for comparison purposes.
As in Chapter 6 this is a single-blind clinical trial, subjects were randomly assigned to a Strip group
(30 subjects) or a Tray group (10 subjects) following screening for tetracycline staining. Subjects
used their respective products for approximately 6 months, with clinical safety and efficacy
measurements taken at the end of each month.
The strip product was used for 30 minutes, twice daily (maxillary arch only). The tray product was
used for 2 hours daily (maxillary arch only). Treatment efficacy was determined by the tooth color
change from baseline using an expanded Vita Shade guide. The Strip group averaged greater
shade reduction compared to the day wear Tray group at the Months 1, 2, and 3 visits, respectively.
After Month 3, there were no significant between-group differences in shade. Of the subjects in the
Strip group, 65% reached B1 tooth color by Month 6, while 43% of subjects in Tray group obtained
this result after 6 months. Both treatments were generally well tolerated. Mild and transient tooth
211
sensitivity (40-47%) and oral irritation (30-47%) were the most common adverse events associated
with daily bleaching, yet neither affected study participation. Both the 6.5% H2O2 experimental
bleaching strip and daywear marketed tray-based carbamide peroxide system provided significant
tooth whitening in subjects with tetracycline stain. The Strip group obtained the results in a shorter
time compared to the daywear tray group.
In this study, onset of shade improvement was earlier, and the magnitude of the change was
greater with strips compared to trays. Through Month 3, the strip group exhibited a statistically
significant (p < 0.05) 1.3 to 3.2 shade improvement relative to the tray control. What accounted for
the significant between-group differences in shade improvement seen early in treatment?
One
likely explanation is that twice a day use of a strip for 30 minutes applied a higher concentration of
peroxide more frequently compared to 2-hours of continuous tray use of the lower concentration
carbamide peroxide gel. Other factors could have contributed to these findings, including the small
sample size in the tray group, differences in the tetracycline staining at baseline, and/or compliance
(strips versus the day wear regimen used for the trays). However, shade guides represent an
imperfect measure of efficacy, especially for complex clinical presentations like those seen with
tetracycline staining. As such, the comparative effectiveness of outcomes must be evaluated with
caution because causality cannot be assessed from multi-factorial research like this clinical trial.
This study provides new evidence of an expanded safety in-use with strip-based tooth whitening.
Both bleaching systems in this trial were well tolerated with daily use over a 6-month treatment
period. No subjects in either group discontinued treatment early due to product-related adverse
events. For the tray system, these findings corroborate other reports of safe continuous daytime
use of 10% carbamide peroxide on tetracycline stain
23,24
. The research provides additional
assurance of the clinical safety of this 10% carbamide peroxide tray system with conventional use
over a few weeks, and longer term use for treatment of tetracycline staining. For the strip system,
the findings provide first evidence of in-use clinical safety with extended treatment. Long term
clinical trials of this duration may be particularly relevant in establishing clinical safety associated
212
with routine treatment, as a research model that evaluates extreme (intentional or unintentional)
use. Such research may only be appropriate with populations such as this one, where long-term
treatment is common and/or necessary to achieve a desired endpoint, where ethical and
experimental controls are adequate to interpret outcomes, and where rigorous and sufficient exit
criteria are established to assure in-use safety.
Under these conditions, longer duration trials
represent a “torture test” of sorts, offering additional insight on short-term clinical safety.
Tetracycline staining is complex, and may necessitate extensive esthetic intervention.
Vital
bleaching with professional tray or strip systems can yield an evident improvement in appearance
within a few weeks. This non-invasive treatment may need to continue over an extended period.
Some individuals will show favorable response after 3-4 months, after which treatment may be
discontinued.
Duration may be difficult to predict, given the variable clinical manifestations of
tetracycline staining. This study confirms that hydrogen peroxide will penetrate enamel and oxidize
dentin. Even with long term exposure to these various whitening regimens no adverse results were
noted.
In Chapter 8 we explore a new delivery system for tooth whitening. This is one of the first studies to
do a direct comparison of two paint-on delivery systems. The latest inclusion to OTC products is a
Brush technique. This technique is non-tray based paint on application. These products include a
19% sodium percarbonate film (5.3% hydrogen peroxide) along with an 18% carbamide peroxide
paint-on gel. The advantages to the paint- on products are ease of use as well as the elimination of
the need for a tray. These systems also limit gingival exposure. There is little data on efficacy of
these products. The objective of this trial was to compare the safety and whitening efficacy of an
experimental liquid strip (four weeks of use) to Colgate Simply White (three weeks of use).
This was a randomized, controlled, double-blind, parallel, single-center study. Fifty (50) generally
healthy subjects who desired to have their teeth whitened were enrolled in the study. Subjects who
qualified for the study based on the results of their Baseline visit were randomly assigned to one of
213
two treatment groups. Data was obtained using a HC2500 CCD high resolution digital camera
manufactured by Fuji. It was equipped with a Fujinon A8x12BMD, 1:2.8/12-96mm zoom lens and a
linear polarizer to permit cross-polarized light. Two 150-watt lights located on each side of a CCD
camera provided the lighting. The unit was connected to a personal computer which recorded and
analyzed the images. Prior to daily use, the system was calibrated to assure proper operation.
Additionally, a color standard was centered and imaged every hour, and then was removed prior to
imaging subjects. Maxillary anterior facial surfaces were measured for tooth color using the digital
image technology. One color value (L* a* b*) was generated from the complete surface of the
measured teeth.
At the Week 4 visit, only the Experimental Film group was effective in whitening teeth as measured
by mean change in L* (lightness) from Baseline (p-value < 0.0001 from Table 7). The Experimental
Film group provided more than 4 times greater improvement in lightness (L*) when compared to
the Colgate Simply White group with estimated means and standard errors of 1.065± 0.135 and
0.263 ± 0.146, respectively. The treatment comparison for L* was statistically significant (p-value
= 0.0003 from Table 12). Only the Experimental Film group effective in whitening teeth as
measured by mean change in a* (redness) from Baseline (p-value = 0.0003 from Table 8). The
Experimental Film group provided more than 3.8 times greater improvement in redness (a*) when
compared to the Colgate Simply White group with estimated means and standard errors of –0.397
± 0.072 and –0.104 ± 0.078, respectively. The treatment comparison for a* was statistically
significant (p-value = 0.0099 from Table 13). Both treatments were effective in whitening teeth as
measured by mean change in W* (composite whiteness) from Baseline with p-values ≤ 0.0029
(Table 9). The Experimental Film group provided more than 4.2 times greater improvement in
composite whiteness (W*) when compared to the Colgate Simply White group with estimated
means and standard errors of
–1.385 ± 0.146 and –0.325 ± 0.158, respectively. The treatment comparison for W* was
214
statistically significant (p-value < 0.0001 from Table 14). Both treatments were effective at
increasing overall color change (E*) with p-values < 0.0001 (Table 10). The Experimental Film
group provided more than 1.9 times greater overall color change (E*) when compared to the
Colgate Simply White group with estimated means and standard errors of 1.534 ± 0.147 and 0.788
± 0.160, respectively. The treatment comparison for E* was statistically significant (p-value =
0.0020 from Table 15). This study indicated that the 19% sodium percarbonate film (5.3%
hydrogen peroxide) paint-on whitening product was affective in whitening teeth, however neither
system tested was as affective as the tray or strip systems previously tested.
In Chapter 9 we explore the rebound that occurs post bleaching as well as methods to limit its
affect. A randomized, parallel, examiner-blind clinical study was conducted to examine the ability of
2 toothbrushes to maintain teeth whitening after at-home bleaching. Forty subjects used a 15%
carbamide peroxide tray bleaching system at home for 2 weeks per the manufacturer’s instructions
and then were randomly assigned to use either the Sonicare® Advance power toothbrush or a
manual toothbrush as part of their home oral hygiene routine for 6 months. The color of the labial
surfaces of the subjects’ maxillary anterior dentition was assessed before bleaching and
immediately, 2 months, 3 months, and 6 months after bleaching. Color was assessed by
comparison with Vita® Classical shade tabs and by digital image analysis in the CIE L*a*b* color
space. Both groups demonstrated a rebound effect at the 2-month visit and beyond, with mean Vita
shade scores significantly higher than immediately after bleaching. At the 6-month evaluation, there
was a significant difference in the amount of rebound in each group. Specifically, the rebound of the
Sonicare brush group was on average 1.12 Vita shades less than that of the manual brush group.
The 6-month difference was confirmed through digital image analysis, with the Sonicare brush
group 4.8 L* units lighter, corresponding to 2 Vita shades, and 2.1 b* units less yellow than the
manual brush group. This clinical trial demonstrates that the Sonicare Advance toothbrush better
maintains whitening after bleaching treatment than a manual toothbrush.
215
The analyses of the digital images and the Vita shade data both show the Sonicare toothbrush to
be superior to a manual toothbrush at maintaining whitening 6 months after bleaching. While this is
the first study examining the effect of Sonicare on maintaining whitening, there are other data on
the effect of a manual toothbrush. Matis and colleagues, for example, report an increase of 5.2 L*
units and 2.9 shade guide units only 6 weeks after a 2-week bleaching regimen using 15%
carbamide peroxide. Our results show a more modest but still measurable rebound effect for
manual brushing. The estimated 6-month Vita shade difference between groups was larger in the
digital analysis (2 Vita shades) than in the Vita shade analysis (1.12 Vita shades). This difference in
estimates may be the result of the varying precision and accuracy of the 2 efficacy measures. We
additionally note that the ordering of the Vita Classical shade guide does not follow the order
suggested by digital image analysis of the shade tabs. In particular, ranking the tabs by decreasing
luminance L*, that is the pure value axis of the L*a*b* color sphere, suggests not only that the color
tabs are incorrectly ordered but also that the color change between tabs is nonlinear. Similar
observations have been reported by O’Brien and colleagues and Paravina and colleagues. These
factors also may contribute to the difference in estimates between the 2 efficacy measures.
This study is important in a number of ways. It confirms that post bleaching rebound occurs as soon
as 1 month after bleaching and this rebound continues at a slower rate up to 6 month. Secondly this
data questions the degree of rebound reported in other studies. Finally this study brings in question
the adequacy of the value ordered shade guide in its present form for bleaching studies.
In Chapter 10 an in vitro study was performed to measure the temperature increase in pulp
chamber produced by Zoom light (mercury halide) and to investigate the influence of this light in
conjunction with the application of bleaching gel on the intrapulpal temperature. The Zoom! Light
was designed specifically for tooth bleaching. The results achieved by this study indicate that
although previous reports showed significant temperature rise on the tooth surface our results
demonstrate that the intrapulpal temperature increases only slightly during the exposure time.
Therefore the Zoom light was found to cause only a slight increase in intrapulpal temperature. The
216
use of the light and gel demonstrated a significantly higher temperature increase than the light
alone. However, this increase is still lower than the necessary to cause pulpal damage (5.5 °C).
The sensitivity noted during light activated bleaching is most probably increase dehydration on the
surface of the tooth. This may relate to 5°C surface temperature change previously reported on the
enamel surface.
Finally this study supports the clinical observation that light activated bleaching does not result in
long term pulp damage and it suggests that the sensitivity noted during light activated tooth
whitening may be the result of dehydration and not pulpal irritation.
In Chapter 11 an exploratory study was done to assess any surface morphological changes in
tooth enamel after treating with a currently marketed hydrogen peroxide strip bleaching system and
a currently marketed sodium chlorite tray-based system using an SEM Investigation. This study
represents the first paper to evaluate enamel following tooth whitening using both visual analysis
and laser profolometry. In this study the use of a visual scoring system for changes on enamel
morphology indicated that there were no significant changes from the baseline in either the 6%
Hydrogen Peroxide gel group or the 2.5% Sodium Chlorite group. It was also noted that in all
evaluations the roughness observed was superficial in nature and that all teeth varied slightly at
baseline.
The laser profilometry data indicated that there is no statistical difference between the baseline and
21 day samples. This is true for both tooth whitening systems. In both groups the 21 day dosing
has no effect on surface roughness of the exposed teeth.
Using two different measurement techniques the results from both tests have the same conclusion
that 21 day exposure to two different tooth whitening systems had no observable or measurable
adverse effects on enamel.
Conclusions and Recommendations
217
The following conclusions and recommendations may be drawn from our studies on tooth
whitening:
1. The use of a low dose delivery system is adequate to get significant whitening.
2. The use of a polyethylene strip containing 5.3% hydrogen peroxide 30 minutes twice per
day results in significant whitening.
3. This research provides clear evidence of a peroxide concentration whitening response.
Whitening efficacy was greatest for the highest concentration group while the intermediate
concentration group had an intermediate response. This effect most approached linearity at
the earliest time point (Day 7).
4. This clinical research provides evidence of a concentration gradient for whitening response
following use of a low peroxide dose whitening system. As such, this may represent a first
example of concentration ranging for one of the self-directed bleaching systems. There is a
measurable concentration affect during bleaching.
5. The use of a light and/or heat to speed up the oxidation process in tooth whitening is of no
benefit. This was tested using the Halogen. Gas Plasma and Metal Halide light sources.
Dehydration appears to cause the initial improvement that is noted immediately post
bleaching.
6. The use of a mercury halide light for tooth whitening does not result in pulpal temperatures
that would cause irreversible pulp damage but might be able to result in dehydration of
exposed teeth.
7. Our data demonstrates the difficulty, regardless of the delivery system, in bleaching
tetracycline stained teeth. This confirms that the peroxide does penetrate to the dentin and
that the oxidation process affects the color of the stained dentin. It also confirms that this is
a slow process and requires extended exposure.
8. Long term exposure (6 month continuous use) to either 10% carbamide peroxide in a tray
system or 6.5% hydrogen peroxide strip resulted in no serious adverse events. This study
218
represents the largest sample size for this type of study and the first to use the strip delivery
system.
9. Paint-on whitening systems vary in effectiveness and none of those tested equal the
efficacy found with the tray or strip systems.
10. Post bleaching rebound occurs as soon as 1 month after bleaching and this rebound
continues at a slower rate up to 6 month.
11. The adequacy of the value ordered shade guide in its present form for bleaching studies is
inadequate. This ordering on the shades is incorrect when checked using digital L*a*b*
analysis. The ADA needs to re-evaluate its requirement for this method of evaluation in
order to obtain ADA approval for tooth whitening systems.
12. Tooth whitening systems tested had no observable or measurable adverse effects on
enamel.
Acknowledgements
I wish to express my sincere gratitude to all who contributed to this work.
Prof. Dr Marco Ferrari who has supported me in many ways both as a friend and fellow researcher.
He has encouraged me to complete this thesis and pushed me to become a better scientist, as he
pushes himself. He has always been there when I have needed advise and I value him dearly.
Prof. Dr C.L. Davidson who has inspired me as a researcher and who I am always trying to emulate
in both my research and in my life.
Dr. Robert Gerlach, my good friend and fellow researcher. We have spent many hours discussing
our projects and he is a constant source of advice and friendship.
Dr’s Ferreria and Sharma who are wonderful young investigators always willing to help and always
wanting to learn.
219
Isabella Desir, my staff assistant, who is willing to put in long hours and always with a smile.
To my family that has always been there when I need them and support me in every way. To my
wife, Karen, who has been with me through it all and is a constant source of inspiration to me. My
children, Kurt and Chrissy; they put life in perspective. My family is most important to me and I
apologize to all of them for the hours of travel and study that have kept me from them.
I would also to thank the members of the committee, Prof Piero Tosi, Rector of the
University of Siena, to Prof Alberto Auteri, Dean of the Faculty of Medicine, University of
Siena, to Prof Egidio Bertelli, vice-Dean of the Faculty of Medicine and Director of the
Department of Dental Science, and to Prof Marco Ferrari, Pro-Rector for international
affairs and President of Dental School, University of Siena for their support with this thesis.
CURRICULUM VITAE
Gerard Kugel, D.M.D., M.S.,
F.A.C.D., F.I.C.D., F.A.G.D., F.A.D.M.
171 Burlington Street
Lexington, MA 02173
(781) 861-1935
EDUCATION
Tufts University School of Dental Medicine
Boston, Massachusetts
D.M.D., Ph.D. Program, 1981-1985
D.M.D., 1985
Sackler School of Graduate Biomedical
Sciences
Department of Anatomy and Cellular Biology
Tufts University
Boston, Massachusetts
M.S., 1993
220
Cornell University Graduate School of
Medical Sciences
Department of Neurobiology
New York, NY
Ph.D. candidate, 1977-1979 (transferred)
WORK EXPERIENCE
Rutgers University
New Brunswick, NJ
B.S. Biology and Psychology
1976
Associate Dean for Research
Tufts University School of Dental Medicine
Boston, Massachusetts
March 2001 – Present
Visiting Professor, Restorative Dentistry
University of Siena, Siena, Italy
1993 - Present
Head of the Division of Operative Dentistry
Tufts University School of Dental Medicine
Boston, Massachusetts
April 1988 – Present
Private Practice
Boston Center for Oral Health
400 Commonwealth Avenue
Boston, Massachusetts 02115
September 1988 – Present
221
PUBLICATIONS Kugel G, PapathanasiouA, Williams III A J, Anderson C, Clinical
Evaluation of Chemical And Light-Activated Tooth Whitening
Systems, Compendium Accepted July 2004.
Ferrari M, Kugel G, Cagidiaco M C, Barker M L, Gerlach R W,
Clinical Trial Evaluating the Peroxide Concentration Response of
Whitening Strips Over 28 Days, Am J Dent. In Press
Kugel G, Gerlach R W, Aboushala A, Susana Ferreira-Martin,
Marco Ferrari,The Long term use of 6.5% Hydrogen Peroxide
Bleaching Strips on Tetracycline Stain: A controlled Clinical Study,
J of Esth and Rest Dent, May-04. Accepted
Kugel G, What You Need to Know When Choosing a Material,
Dentist’s Money Digest, pages 24-25, April 2004
Kugel G, Aboushala A, Sharma S, Ferreira S, Anderson C,
Maintenance of Whitening with a Power Toothbrush After
Bleaching Treatment, Compendium, Vol. 25, No. 2, pages 119131, February 2004.
Ferreira S, Kugel G, A Simple Review of LED Curing Lights,
Contemporary Esthetics and Restorative Practice, pages 52-56,
November 2003.
Aboushala A, Kugel G, Meta N, Using a Novel Bite Plate to Alleviate
Chronic Bruxism Symtoms, Contemporary Esthetics and Restorative
Practice, Vol 7, No. 10 Pages 72-78, October 2003
Zhang Q, Rosenberg M, Kugel G, Agarwal R, Phillips j, Kumar S,
Effect of Nitrous Oxide on Intracellular Events of GT1-7 GnRHsecreting Neurons, Anesth Prog 50:53-61, 2003
Zhang Q, Bratton G, Agarwal R, Calise D, Kugel G, Wan Y, Kumar A,
Lead-induced cell singnaling cascades in GT1-7 cells, Brain Research
Bulletin, 61, pages 207-217, 2003
Kugel G, Perry R, Restoring Anterior Maxillary Dentition Using
Alumina and Zirconia –Based, Compendium, Vol. 24, No. 8, pages
569-580, August 2003.
Zhang Q, Bratton G, Agarwal R, Calise D, Kugel G, Wan Y, Kumar A.
Lead-induced cell signaling cascades in GT1-7 cells, Brain Research
Bulletin Vol. 61, No. 207-217, April 2003
222
Kugel G, Over-the-Counter Toothwhitening Systems, Compendium
Vol. 24, No 4A. April 2003
Fabianelli A, Kugel G, Ferrari Marco, Efficacy of self-etching primer on
sealing margins of Class II restorations, American Journal of Dentistry
Vol 16, No.1, pages 37-41, February 2003.
Kugel G, Perry R, Direct Composite Resins: An Update,
Compendium. Vol. 23, No. 7. July 2002.
Kugel G, Boghosian A. Impact of the Sonicare® Toothbrush on
Plaque and Gingivitis, Compendium. Vol. 23, No. 7. July 2002.
Suppl. 1
Kugel G, Boghosian A. Effects of the Sonicare® Toothbrush for
Specific Indications, Compendium. Vol. 23, No. 7. July 2002.
Suppl. 1
Papathanasiou A, Kastali S, Perry R, Kugel G, Clinical Evaluation
of a 35% Hydrogen Peroxide In-Office Whitening System,
Compendium. Vol. 23, No. 4. April 2002.
Perry R, Kugel G, Success with Inlays/Onlays: The Seven
Essentials, Compendium. Vol 23, No. 3. March 2002.
Gheewalla E, Perry R., Kugel G, Effects of Three Electric
Toothbrushes on Orthodontic Bracket Retention, Journal of
Clinical Orthodontics, Volume XXXVI No. 2, January 2002
Fabianelli A, Kugel G, Ferrari M. Efficacy of self-etching primer on
sealing margins of CI II restorations. American Journal of Dentistry.
Accepted 2002.
Ferrari M, Cagidiaco M, Kugel G, Dolci G. Evaluation concentration
response after 4 weeks treatment with a flexible, polyethylene
whitening strips. Compendium/Special Issue Volume 22, No. 2,
2001.
Kugel G, Aboushala A, Zhou X, Gerlach R. Daily Use of Whitening
Strips on Tetracycline-Stained Teeth: Comparative Results After 2
Months. Compendium Volume 22, No. 2, 2001.
223
Kugel, G., Garcia-Godoy F., Direct Esthetic Adhesive
Restorative Materials A Review. The Indian Dentist, No. 7-13,
21, April – June 2001
Papathanasiou A., Bardwell D, Kugel G., A Clinical Study
Evaluation a New Chairside and Take-Home Whitening System.
Compendium of Continuing Education in Dentistry, Volume 22,
No. 4:289-300, April 2001
Goracci C., Gheewalla R., Kugel G., Ferrari M., Orthodonticrestorative treatment of chipped or worn incisors. American
Journal of Dentistry, Volume 14, No. 50-55, February, 2001
Kugel G., Provisional Esthetic Enhancements Following Initial
Treatment to Correct Anterior Wear, Esthetic Technique,
Volume 1, No. 1:3-7, April 2001
Leinfelder K, Kugel G., Flowable Compomers, Dialogues in
Esthetic Dentistry, Volume 2, No. 1:7-8, April 2001
Javaheri DS, Kugel G., Janis JN. Current Status of At-Home
Bleaching. Practical Procedures and Aesthetic Dentistry,
Volume 13, No. 1:10-13, January/February 2001
Perry R, Kugel G. Two-Year Clinical Evaluation of a HighDensity Posterior Restorative Material.
Compendium of
Continuing Education in Dentistry, Volume 21,No. 12:10671080, December 2000
Weinstock E, Skoulas A, Kugel G, Aboushala A. The Myth of
Dentist-Patient Confidentiality.
Compendium of Continuing
Education in Dentistry, Volume 21, No. 12:1056-1064, December
2000
Kugel G. Direct and Indirect Adhesive Restorative Materials: A
Review. American Journal of Dentistry, Volume 13, Special
Issue, No. 35-40, November, 2000.
224
Kugel G, Garcia-Godoy F. Direct and Indirect Esthetic Adhesive
Restorative Materials: A Review. Dental News, Volume VII,
Number 3:29-39, 2000
Perry R, Kugel G, Kunzelmann KH, Flessa HP, Estafan D.
Composite Restoration Wear Analysis: Conventional Methods
vs. Three-Dimensional Laser Digitizer. JADA, Vol. 131, No. 10:,
p.1472-1477, October 2000.
Papathanasiou A, Bardwell D, Kugel G. Combining In-Office and
Take-Home Whitening Systems. Contemporary Esthetics and
Restorative Practice. Vol. 4. No. 8: 88, September 2000
Kugel G, Garcia-Godoy, F. Direct Esthetic Adhesive Restorative
Materials: A Review. Contemporary Esthetics and Restorative
Practice. Vol. 4. No. 9: 6-10, September 2000.
Kugel G, Kastali S. Tooth-Whitening Efficacy and Safety: A
Randomized and Controlled Clinical Trial. Compendium 21, S29,
16-21, July 2000
Kugel G. Nontray Whitening. Chairside: Compendium. Vol. 21, No.
6, 524-528, June 2000.
Kugel G, Ferrari M. The Science of Bonding: From First to Sixth
Generation. JADA, Vol. 131:20S-25S, June 2000.
Kugel G, Perry R, Ferrari M, Lalicata P. Disinfection and Communication
Practices: A Survey of U.S. Dental Laboratories. JADA, Vol. 131:786-792, June
2000.
Zervou C, Kugel G, Leone C, Zavras A, Doherty E. Enameloplasty
Effects on Microleakage of Pit and Fissure Sealants Under Load: an
In-Vitro Study. The Journal of Clinical Pediatric Dentistry. 24(4): 279285, April 2000
Ferrari M, Mannocci F, Mason PN, Kugel G, In vitro leakage of
resin-bonded all-porcelain crowns.
Journal of Adhesive
Dentistry, 1:3:233-242, 1999.
Kugel G, Swift EJ, Sorenson JA, Dunne JT, Tucker JH. A
prospective clinical evaluation of electronically mixed polyvinyl
siloxane impression materials. Compendium, S24:2-22, 1999.
225
Petridis H, Hirayama H, Kugel G, Habib C, Garefis P. Shear
bond strength of techniques for bonding esthetic veneers to
metal. Journal of Prosthetic Dentistry, 82:5:608-614, 1999.
Ferrari M, Cagidiaco MC, Kugel G, Davidson CL. Clinical
evaluation of a one-bottle bonding system for desensitizing
exposed roots. American Journal of Dentistry, 12:5:243-249,
1999.
Kugel G, Perry R, Hoang E, Hoang T, Ferrari M. Dyract
Compomer: Comparison of Total Etch vs. No Etch Technique.
Journal of the Academy of General Dentistry, Volume 46,
Number 6:604-606, Nov-Dec 1998.
Kugel G. Clinical Testing of Surefil. Journal of International
Dental Symposia, 5:7, 1998.
Ferrari M, Mason PN, Fabranelli A, Mannocci F, Kugel G,
Davidson CL. Influence of Tissue Characteristics at Margins on
Leakage of Class II Indirect Restorations, Accepted, American
Journal of Dentistry, 1998.
Ferrari M, Kugel G. Handling of Composites in Posterior Teeth,
Compendium, 19:879-892, 1998.
Kugel G, Ferrari M. AelitefloTM. To Base or Not to Base, There
Is No Question!, Restorative Quarterly, 1:7, April 1998.
Karuri AR, Kugel G, Engelking LR, Kumar MSA. Alterations in
Catecholamine Turnover Rate in Specific Regions of the Rat Brain
Following Acute Exposure to Nitrous Oxide, Brain Research
Bulletin, 45:557-561, 1998.
Kugel G, Minimale Präpartion für Frontzahnrestaurationen
(Minimal Preparation for Anterior Restorations), Phillip Journal,
14:383-384, 1997.
Donly K, Vargas M, Meckes M, Sharma A, Kugel G, Hurley E. InVitro Comparison of Restoration Wear and Tensile Strength
Following Extended Brushing with Sonicare and Manual
Toothbrushes, Journal of Clinical Dentistry, 8:1:30-35, 1997.
Zammitti S, Habib C, Kugel G. Use of Environmental Scanning
Electron Microscopy to Evaluate Dental Stain Removal, Journal
of Clinical Dent, 8:1: 20-25, Winter 1997.
226
Samadzadeh A, Aboushala A, Hurley E, Kugel G. A Comparison
of Fracture Strength Between PMMA and Resin-Based Provisional
Restorations Reinforced with Plasma-Treated Woven Polyethylene
Fiber, Journal of Prosthetic Dentistry, 78:5:447-450, November
1997.
Kugel G, Perry R, Putignamo A, Ferrari M. Valutazione clinica a due
anni dello spectrumTPH nel restauro di lesioni cariose in cavità di classe
II in denti permanenti.. Quintessence International, Settembre/Ottobre
1997.
Ferrari M, Kugel G. Handling of Composites in Posterior Teeth,
Compendium, 19:879-892, 1998.
Kugel G. Buying Right, Journal of the Massachusetts Dental
Society, 46:2:12-14, October 1997.
Perry RD, Kugel G, Habib CM, McGarry P, Settembrini L. A
Two Year Clinical Evaluation of TPH for Restoration of Class II
Carious Lesions in Permanent Teeth, General Dentistry, 45:
4:344-349, July/August 1997.
Ferrari M, Mannocci F, Cagidiaco MC, Kugel G. Short-Term
Assessment of Leakage of Class V Composite Restorations
Placed In Vivo, Clinical Oral Investigation, 1:2:61-64, June 1997.
Kugel G, Perry R, Hoang E. Effective Tooth Bleaching in 5 Days:
Using a Combined In-Office and At-Home Bleaching System,
Compendium, 18:4:378-383, April 1997.
Abdel-Latif M, Kugel G, Norris L, Kabani S. Nd: Yag Laser and
Conventional Techniques in Bone Surgery, Cairo Dental Journal,
13:1:225-230, 1997.
Kugel G.
Classification and Application of Cementation
Alternatives, Signature: The Art and Science of Modern Dentistry,
Fall 1997.
Ferrari, M, Cagidiaco, Kugel G, Davidson CL. Dentin Infiltration by
Three Adhesive Systems in Clinical and Laboratory Conditions,
American Journal of Dentistry, 9:6:240-244, December 1996.
Weiner RS, Weiner LK, Kugel G. Teaching the Use of Bases and
Liners: A Survey of North American Dental Schools, JADA,
127:11:1640-1645, November 1996.
227
Kugel G, Perry RD, Habib CM, McGarry P. A Two Year Clinical
Evaluation of Pertac Hybrid for Restoration of Class II Carious
Lesions in Permanent Teeth, Compendium, November 1996.
Ferrari M, Cagidiaco MC, Kugel G. Leakage of Class V Resin
Composite Restorations Placed in Vivo, American Journal of
Dentistry, October 1996.
Aboushala A, Kugel G, Hurley E. Class II Composite Resin
Restorations Using Glass-Ionomer Liners: Microleakage Studies,
Journal of Clinical Pediatric Dentistry, 21:1:67-70, Fall 1996.
Agawal RK, Kugel G, Karuri A, Gwosdow AR, Kumar, MSA.
Effects of Low and High Doses of Nitrous Oxide on
Preproenkephalin on RNA and Its Peptide Methionine
Enkephalin Levels In the Hypothalamus, Brain Research,
730:1,2:47-51, August 1996.
Ferrari M, Cagidiaco MC, Kugel G.
All -Ceramic Fixed
Restorations: A Preliminary Clinical Evaluation, Practical
Periodontics Aesthetic Dentistry, 8:1:73-80, Jan-Feb 1996.
Habib C, Smith S, Kugel G, Aboushala A. Dimensional Stability of
Elastomeric Impressions After Long-Term Disinfection, Journal of
Prosthetic Dentistry, January 1996.
Ferrari M, Kugel G. IPS - Empress Crowns: Clinical Reports,
Practical Periodontics and Aesthetic Dentistry, 1996.
Kugel G, Bardwell DN. Restoration of a Class V Lesion Using a
New Compomer Material, Signature: The Art and Science of
Modern Dentistry, 14-17, November 1995.
Kugel G. The Changing Face of Oral Health Care, Feature Article,
Tuftonia, 27, Spring 1994.
Ferrari M, Dalloca L, Kugel G, Bertelli E. An Evaluation of the
Effect of the Adhesive Luting on Microleakage of the IPS Empress
Crowns, Practical Periodontics and Aesthetic Dentistry, 6:4:15-24,
May 1994.
Fischman SL, Kugel G, Truelove RB, Nelson BJ, Cancro LP. The
Motivational Benefits of a Dentifrice Containing Baking Soda and
Hydrogen Peroxide Used, The Journal of Clinical Dentistry, 3:3 8892, 1992.
228
Russell DA, Kugel G. Preceptor Program: An Alternative Mode of
Instruction for the Slowly Progressing Dental Student, Journal of
Dental Education, 55:1:36-37, January 1991.
Champion MA, Kugel G, Gruskowski C. Evaluation of a New
Intraoral Isolation Device, Operative Dentistry, 16:181-185, 1991.
Kugel G, Zive M, Agawal RK, Beumer JR, Kumar AM. Effects of
Nitrous Oxide on the Concentration of Opioid Peptides, Substance
P, and LHRH in Brain and -Endorphin in the Pituitary, Anesthesia
Progress, 38:206-211, 1991.
Kugel G, Letelier M, Zive H, King JC. Nitrous Oxide and Infertility,
Anesthesia Progress, 37:4:176-180, July 1990.
Kugel G, Zive M, Norris L. Nitrous Oxide and Occupational
Exposure, Journal of the Society for the Advancement of
Anesthesia in Dentistry, 7:10:266-276, May 1990.
Kugel G, Zive M, Norris L. N2O/O2 - It's No Laughing Matter,
Review Article, Journal of the American Analgesia Society,
24:1:14-16, March 1990.
Kugel G, Norris L, Zive M. Nitrous Oxide; Occupational Exposure:
It's Time to Stop Laughing. Anesthesia Progress, 36:6:252-257,
1989.
King J C, Kugel G, Zahniser D, Wooledge K, Damassa D,
Alexsavich B. 3-D Analyses Reveal Changes in Populations of
LHRH Cell Bodies Following Gonadectomy, Peptides, 8:721-735,
August 1987.
King JC, Lechan RM, Kugel G, Anthony ELP. Acrolein: A Fixative
for - Immunocyto-chemical Localization of Peptides in the Central
Nervous System, The Journal of Histo-chemistry and
Cytochemistry, 31:1:62-68, January 1983.
229
ABSTRACTS
Perry R, Kugel G, Shrama S, Ferreira S, Clinical Evaluation of a LED
Curing Light, Journal of Dental Research, 83: 540 March 2004
Kugel G, Ferreira S, Sharma S, Barker M L, Garlach R W, Comparison of
Daytime and Nighttime Brush-Applied Whitening Systems, Journal of
Dental Research, 83:1912 March 2004
Papathanasiou A, Kastali S, Clinical Evaluation of a New AdhesiveComposite System, Journal of Dental Research, 83:538 March 2004
Petkevis J, Alfaro M, Doherty E H, Kugel G, Kanca J, Self-etch adhesive
bond strength at two time intervals, Journal of Dental Research, 83: 465
March 2004
Bedi A, Hirayama H, Kugel G, Forgione A G, Surface Roughness and
Irregularities of Castings using Different Iinvestment Techniques, Journal
of Dental Research, 83: 1680 March 2004
Kugel G, Papathanasiou, Clinical Evaluation of Two Different In-office
Tooth Whitening Systems, Journal of Dental Research, 28: 897 March
2003
Aboushala, A, Kugel G, Sharma S, Ferreira S, SonicareToothbrush
Whitening Effect after Bleaching Treatment, Journal of Dental Research,
82: 614, March 2003
Anderson C, Kugel G, Aboushala, A, Sharma S, Ferreira S, Rebound
Evaluation of Post-Bleaching Maintenance Utilizing Manual and Electric
Toothbrushes; Quantitative Assessment by Digital Photography, Journal
of Dental Research, 82: 605, March 2003
Kugel G, Aboushala, A, Zhou X, Gerlach R Six-month Continuous Use of
Two At-home Professional Bleaching Systems on Tetracycline Stain,
Journal of Dental Research, 82: 32, March 2003
Anderson C, Kugel G, Ferreira S, Aboushala, A, Sharma S, Six-month
Rebound Evaluation of Subjects Treated with a 15% Carbamide Peroxide
Gel; Quantitative Assessment by Standard Digital Photography, Journal
of Dental Research, 82: 1303, March 2003
Perry R, Papathanasiou A, Kugel G, Davidiian E, A Comparison of Two
Flowable Composite Materials in Posterior Restorations Journal of
Dental Research, 82: 256, March 2003
230
Watts R, Joffre E, Doherty E, Kugel G, Shear Bond Strength Investigation
of an Experimental Self-etching Bonding System, Journal of Dental
Research, 82: 566, March 2003
Anderson C, Kugel G, Perry R, Garcia-Godoy F, Evaluation of an
Experimental One-Step Composite Polishing System, Journal of Dental
Research, 81: 1267, March 2002
Anderson C, Sethi S, Kugel G, Perry R, Garcia-Godoy F, Comparison of
Surface Gloss and Time by Three Composite Polishing Systems,
Journal of Dental Research, 81: 1273, March 2002
Kugel G, Aboushala A, Zhou X, Gerlach R W, Use of Whitening Strips
on etracycline: Results after four months, Journal of Dental Research,
81: 2442, March 2002
Kim M S, Reusch B, Hoffmann H, Doherty E H, Kugel G, Surface
Wettability of Saliva and Blood Plasma During Setting of Impression
Materials, Journal of Dental Research, 81: 2660, March 2002
Nguyen T, Doherty E H, Aboushala A, Kugel G, Perry R, Effect of
Chemomechanical Caries Removal System on Microleakage of
Composite Resin Restorations, Journal of Dental Research, 81: 3391,
March 2002
Anderson C, Kugel G, Rebound Evaluation of Tetracycline Stained
Subjects Treated with a 6.5% Hydrogen Peroxide Gel; Quantitative
Assessment by Standard Digital Photography, Journal of Dental
Research, 81: 3488, March 2002
Perry R, Gheewalla E, Kugel G, A Comparison of Three Electric
Toothbrushes on Orthodontic Bracket Retention, Journal of Dental
Research, 80: 590, 2001
Kim MS, Doherty EH, Kugel, G, Flow Under Pressure of Four Impression
Materials Using Shark-Fin Device, Journal of Dental Research, 80: 624,
2001
Kastali S, Papathanasiou A, Perry R, Kugel G, Clinical Evaluation Of A
Light To Heat Activated Bleaching System, Journal of Dental Research,
80: 926, 2001
231
Kugel G, Kastali S, Sagel P, Gerlach R, Six-Month Clinical Response
with Whitening Strips: Comparison to Placebo, Journal of Dental
Research, 80: 1174, 2001
Lokko NN, Kugel G, Habib C, Doherty E, Rand W, In Vitro Bond Strength
Evaluation of Resin, Modified Glass Ionomer Cements, Journal of Dental
Research, 80: 1304, 2001
Verdier A, Kugel G, Habib C, Comparison of Surface Finish Produced on
Resin Composites following Extended Brushing With A Manual
Toothbrush and Sonicare, Journal of Dental Research, 80: 1337, 2001
Perry R, Kugel G, Aboushala A, Two-Year Clinical Evaluation of a HighDensity Posterior Restorative, Journal of Dental Research, 79:158, 2000.
Fabianelli A, Vichi A, Kugel G, Ferrari M, Influence of Self-etching
Priming Bonding Systems on Sealing Ability of Class II Restorations:
Leakage and SEM Evaluation, Journal of Dental Research, 79:305, 2000.
Bardwell D, Habib C, Kugel G, Mehta N, Leone C, Microleakage of
Previously Restored Class II Restoratives After Exposure to 10%
Carbamide Peroxide, Journal of Dental Research, 79:306, 2000.
Kastali S, Papathanasiou K, Perry R, Kugel G, Clinical Evaluation of a
New Hybrid Composite, Journal of Dental Research, 79:333, 2000.
Zervou C, Kugel G, Leone C, Zavras A, Doherty E, White G.E.,
Enameloplasty and Load Effects on Microleakage of Sealants (in vitro),
Journal of Dental Research, 79:1688, 2000.
Papathanasiou K, Kastali S, Perry R, Kugel G, Clinical Evaluation of Light
Cured Flowable Compomere in Class V Restorations, Journal of Dental
Research, 79:1735, 2000.
Rassovsky M, Hirayama H, Habib C, Kugel G, The Expansion of Various
Luting Agents Used to Cement Post & Core: An in vitro study, Journal of
Dental Research, 79:2327, 2000.
Naidu K, Kugel G, Habib C, Class II Composite Restorations:
Microleakage Using Three Different Curing Systems, Journal of Dental
Research, 79:2466, 2000.
232
Habib C, Kugel G, Effect of Aging on Three Enamel Dentin Adhesive
Systems, Journal of Dental Research, 79:2475, 2000.
Aboushala A, Kugel G, Efthimiadis N, Korchak M, Efficacy of a
Computer-controlled Injection System of Local Anesthesia, in vivo,
Journal of Dental Research, 79:2775, 2000.
Aboushala A, Mehta N, Forgione A, Kugel G, Chapman R. Vertical
Dimension and Electromyography of Masseters in Complete Denture
Patients, Journal of Dental Research, 78:2911, 1999.
Nam C, Kugel G, Habib C. Changes in Enamel Surfaces After Take
Home Bleaching Treatment in vitro, Journal of Dental Research,
78:1695, 1999.
Perry R, Kugel G. One-Year Clinical Evaluation of a High-Density
Posterior Restorative, Journal of Dental Research, 78:1628, 1999.
Lalsingh C, Hurley E, Hassan M, Trushkowsky R, Kugel G,
Leone C. Effects of Curing Lights on Microleakage in Class V
Composite Restorations, Journal of Dental Research 78:1601,
1999.
Papathanasiou A, Kastali G, Kugel G, Bardwell D, Hurley E.
Microleakage Evaluation of Three Class II Composite
Restorative Techniques in vitro, Journal of Dental Research
78:1600, 1999.
Hurley E, Aboushala A, Perry R, Kugel G. Microleakage
in Class II Restorations Using a New Posterior
Composite, Journal of Dental Research 77:487, June
1998.
Drukteinis S, Hurley E, Perry R, Kugel G. The Performance of
Aluminum Oxide and Cojet Microetchant Systems, Journal of
Dental Research 77:506, June 1998.
Gheewalla E, Perry R, Kugel G. Effect of Powered
Toothbrushes on Orthodontic Bracket Adhesion in vivo, Journal
of Dental Research, 77:506, June 1998.
233
Kugel G, Karuri A, Kumar MSA. Alterations in the
Cathecholamine Turnover Rate in Specific Regions of Rat Brain
Following Acute Exposure to Nitrous Oxide, Journal of Dental
Research 77:921, June 1998.
Ferrari M, Mason PN, Fabianelli A, Kugel G, Davidson CL.
Influence of Different Margin Substrates on Leakage of Class II
Indirect Restorations, Journal of Dental Research 77:2248,
June 1998.
Aboushala A, Kugel G, Perry R, Leone C. Resin-Ionomer
Restoration of Molar Furcations in Humans, Journal of Dental
Research 77:2573, June 1998.
Ferrari M, Cagidiaco MC, Kugel G, Davidson CL. Clinical
Evaluation of SB1 Root Desensitization with/without Acid
Etching. Journal of Dental Research 77:2586, June 1998.
Ferrari M, Mannocci F, Innocenti M, Kugel G, Davidson CL.
Clinical Evaluation of Dyract AP and Fuji IX to Build up
Abutments for Porcelain Crowns, Journal of Dental Research
77:2598, June 1998.
Kastali S, Kugel G, Perry R, Papathanassiou A. Combined
In-Office and At-Home Bleaching Systems: An Evaluation,
Journal of Dental Research 77:2604, June 1998.
Perry R, Kugel G, Kastali S. Evaluation of a Non-Hydrogen
Peroxide At-Home Bleaching System, Journal of Dental
Research 77:2605, June 1998.
Kugel G, Squier C. Fact vs. Fiction: The Transfer of
Scientific Knowledge into the Dental Curriculum, Journal of
Dental Research 77:4, March 1998.
Aboushala A, Mehta N, Forgione A, Kugel G, Chapman R,
Clark RE. Vertical Dimension and Electromyography of
Sternocliedomastoids in Complete Denture Patients, Journal
of Dental Research, 77:456, March 1998.
Chafka A, Mehta N, Kugel G, Hayes C, Forgione A. Effect of
Graded Increases in Vertical Dimension on Cervical Flexor
Strength, Journal of Dental Research 77:735, March 1998.
Kugel G, Lalicata PJ, Perry R. Survey of U.S. Dental
Impression Materials and Techniques, Journal of Dental
Research, 76:1343, March 1997.
234
Daryabegi Y, Perry R, and Kugel G. Differences Shear
Bond Strength of Three Dentin Bonding System, Journal of
Dental Research, 76:1387, March 1997.
Fu A, Mehta N, Forgione A, Clark E, Hayes C, Kugel G.
Abdallah E. Maxillomandibular Relationship in TMD Patients
Before and After Short Term Bite Plate Therapy, Journal of
Dental Research, 76:2363, March 1997.
Hoang E, Kugel G. and Perry R. Combined in Office and
Home Applied Bleaching System, Journal of Dental
Research, 76:2476, March 1997.
Perry R, Kugel G, McGarry P, Hurley E. An In Vivo
Subcutaneous Investigation of a Resin-Ionomer, Journal of
Dental Research, 76:2499, March 1997.
Aboushala A, Mehta N, Forgione A, Kugel G. Chapman R.
and Clark RE. Vertical Dimension Effects on
Strenocleidomastoid Strength in Complete Denture Patients,
Journal of Dental Research, 76:3185, March 1997.
Bahram R, Aboushala A, Kugel G, Perry R. Compomer
Effects on Microleakage in Class II Composite Resin
Restorations, Journal of Dental Research, 76:3236, March
1997.
Druktenis S, McGarry P, Aboushala A, Kugel G, Habib C.
Effect of Adhesives on Microleakage Between Dentin and
Light Cured Glass Ionomer Liners, Journal of Dental
Research, 76:3238, March 1997.
Yau L, Perry R, Kugel G. Three Body Wear of Light Cured
Flowable Composites, Journal of Dental Research, 76:3276,
March 1997.
McSweeney T, Perry R, Aboushala A. Kugel G. Different
Liners in Class II Composite Resin Restorations, Journal of
Dental Research, 76:3283, March 1997.
Vaughn V, Kugel G, Perry R, Noonan ST. Measuring Flow
of Elastomeric Impression Materials Using the Shark Fin
Device, Journal of Dental Research, 76:3292, March 1997.
Ferrari M, Cagidiaco MC, Kugel G, Davidson CL. Dentin
Infiltration by Three Adhesive Systems in Clinical and
Laboratory Conditions, American Journal of Dentistry, 9:6,
December 1996.
235
Habib C, Smith C, Kugel G, Aboushala A. Comparison of
Dimensional Stability of Elastomeric Impression After
Immersion Disinfection, Journal of Dental Research, 75:357,
March 1996.
Sharma A, Kugel G, Hurley E. Evaluation of the Effect of
Sonic and Manual Toothbrushes on Cemented Crowns,
Journal of Dental Research, 75:361, March 1996.
Samadzadeh A, Aboushala A, Kugel G. A Comparison of
Fracture Strengths Between PMMA and Resin-Based
Provisional Restorations Reinforced with Plasma-Treated
Woven Polyethylene Fiber, Journal of Dental Research,
75:369, March 1996.
Marcus A, Bender G, McGarry P, Kugel G. Comparison of
Dental Cements Shear Bond Strength to a Semi-Precious
Alloy Surface In Vitro, Journal of Dental Research, 75:398,
March 1996.
Vaughn V, Bardwell D, Kugel G, Perilli. Follow-Up
Comparing Three Polishing Systems to Glazed Porcelain
Utilizing Profilometry, Journal of Dental Research, 75:1038,
March 1996.
McSweeney T, Perry R, Kugel G. Profilometry Comparison
of Polished Porcelain. Journal of Dental Research, 75:1039,
March 1996.
Bhatt A, Gheewalla E, Perry R, Kugel G. Comparison of a
Compomer and Resin Cement for Bonding of Orthodontic
Bracket, Journal of Dental Research, 75:1259, March 1996.
Perry R, Kugel G, Kunzelmann KH, Flessa HP, Mehi A,
Hickel R. A Composite Study of Wear Analysis Methods of
In-Vivo Posterior Composite Restorations, Journal of Dental
Research, 75:1910, March 1996.
Lee K, Aboushala A, Kugel G. Microleakage of Class II
Composite Resin Restorations Using Different Placement
and Light Cure Techniques In Vitro, Journal of Dental
Research, 75:2168, March 1996.
236
Perry R, Kugel G, Kunzelmann KH, McGarry P. Two-Year
Evaluation of a Hybrid Composite for Posterior Restorations.
Journal of Dental Research, 75:2181, March 1996.
Prezioso A, Kugel G, Perry R. Microleakage: A Comparison
of Three Chairside Ceramic Repair Kits In Vitro. Journal of
Dental Research, 75:2965, March 1996.
Hoang E, Perry R, Aboushala A, Kugel G. Comparison of
Microleakage Using Etched and Non-Etched Techniques in
Class V Restorations, Journal of Dental Research, 75:2966,
March 1996.
Vaughn V, Aboushala A, Habib C, Kugel G. Comparison
Between Two Sealants for Reducing Class II Composite Resin
Microleakage In Vitro, Journal of Dental Research, 75:3017,
March 1996.
Beaber W, Arbree N, Kugel G. Pilot study: A Skin Protectant
for Latex-Glove-Induced Dermal Sensitivity Reaction, Journal
of Dental Research, 75:3185, March 1996.
Smith N, Sharma A, Habib C, Perry R, Kugel G. Comparison
of a Cordless Curing Light and a Single Unit Curing Light,
Journal of Dental Research, 74:495, March 1995.
Vaughn V, Bardwell D, Kugel G, Perilli R. Comparing Three
Polishing Systems to Glazed Porcelain Utilizing Profilometry,
Journal of Dental Research, 74:220, March 1995.
Resnick S, Prezioso A, Kugel G, Smith C, McGarry P. Effect of
Surface Treatments on Microleakage of Composite - Ceramic
Repair, Journal of Dental Research,. 74:228, March 1995.
Joseph A, Perry R, Kugel G, Smith C. Effects of Varying
Concentrations of 4-META
on Tensile Strength on Bonding Composite to Dentin, Journal
of Dental Research, 74:495, March 1995.
Morrill F, Galburt R, Kugel G, Habib CM. Comparison of Bond
Strength Formed Between Amalgam and Composite by
Varying the Ratio of Spherical to Lathe Cut Particle, Journal of
Dental Research, 74: 743, March 1995.
Zammitti S, Kugel G, Habib C. Environmental Scanning
Electron Microscope Study Evaluating the Efficacy of a Sonic
Toothbrush, Journal of Dental Research, 74:970, March 1995.
237
Mehta N, Kugel G, Lamkin J, Bansal S, Forgione A.
Effectiveness of Electronic Anesthesia in Controlling Pain
During Periodontal Scaling, Journal of Dental Research,
74:972, March 1995.
McSweeney T, Perry R, Kugel G. Tensile Strength of Dentin
Bonding Agents With Different Acid Etch Preparations, Journal
of Dental Research, 74:1107, March 1995.
Supnet L, Bhatt A, Aboushala A, Bardwell D, Smith C, Kugel G.
Microleakage of Three Experimental Dentin Primers With
Altered HEMA Concentrations, Journal of Dental Research,
74:1112, March 1995.
Perry R, Kugel G, Habib C, McGarry P, Champion M. TwoYear Evaluation of a Hybrid Composite for Posterior
Restorations, Journal of Dental Research, 74:1224, March
1995.
Kugel G, Court MH, Agarwal RK, Kumar MSA. Effects of
Nitrous Oxide on Preproenkephalia mRNA and Methionine
Enkephalin, Journal of Dental Research, 74:1309, March 1995.
Bahram R, Kugel G, Mclure T, Habib C. Comparison of
Polishability of Three Composite Materials, Journal of Dental
Research, 74:1386, March 1995.
Aboushala A, Kugel G, Habib C. Microleakage Class II
Composite Restorations Using Glass Ionomer Liner, Journal of
Dental Research, 74:1398, March 1995.
Shayegan A, Aboushala A, Kugel G. Microleakage of Class II
Composite Restoration Using a Glass Ionomer, Liner and
Base, Journal of Dental Research, 74:1399, March 1995.
Smith N, Gheewalla E, Kugel G, Habib C. Evaluation of Effects
of a Sonic Toothbrush
on the Bond Strength of Bonded Orthodontic Appliances,
Journal of Dental Research, 74:1414, March 1995.
Ferrari M, Kugel G, Davidson CL. In Vivo and In Vitro Hybrid
Layer Formation, IADR-CED Meeting, Lubiana, 1995.
Habib C, Smith C, Kugel G, Aboushala A. Dimensional
Stability of Elastomeric Impressions After Long Term
Disinfection, Journal of Dental Research, 73:409, 1994.
238
Morrill F, Galburt R, Kugel G, Zive M, Habib C. Comparison of
Different Shaped Particles of Amalgam Alloy Bonded to
Composite and Dentin with 4-Methacryloxyethyl Trimellitate
Anhydride, Journal of Dental Research, 73:221, 1994.
Bahram R, Kugel G, Zive M, Habib C, Golden M. Comparison
of Bond Strength of Two Dentin Bonding Systems to Radicular
Dentin, Journal of Dental Research, 73:199, 1994.
Mehta N, Kugel G, Al Shuria A, Sands M, Forgione A. Effect of
Electronic Anesthesia T.E.N.S. on T.M.J. and Orofacial Pain,
Journal of Dental Research, 73:358, 1994.
Kugel G, Smith N, Sharma A, Habib C, Perry R. A Comparison
of a Cordless Curing Light and a Single Unit Curing Light,
Journal of Dental Research, 73:406, 1994.
Zive M, Champion M, Kugel G. Marginal Microleakage Around
Tooth-Colored Inlay Systems, Journal of Dental Research,
72:307, 1993.
Ghazinouri R, Zammitti S, Zive M, Kugel G, Habib C.
Microleakage Using a New Technique for Posterior Composite
Restorations, Journal of Dental Research, 72:308, 1993.
McGarry P, Kugel G, Habib C, Perry R. Clinical Evaluation of a
Small Particle Composite to Treat Root Caries & Cervical
Erosions, Journal of Dental Research, 72:349, 1993.
Bellucci A, Kugel G, Habib C, Zive M. Adhesion Strengths of
Four Luting Agents with Various Core Buildup Materials,
Journal of Dental Research, 72:361, 1993.
Habib C, Kugel G, Herr K. Two-Year Evaluation of
Composite Restoration of Root Surface Caries After
Chemo-Mechanical Excavation, Journal of Dental
Research, 72:381, 1993.
Kugel G, Habib C, Zammitti S. Enamel and Dentin
Surfaces After Treatment With Adhesion Conditioners
Using the Environmental SEM, Journal of Dental Research,
72:387, 1993.
Agarwal R, Zive M, Kugel G, Gwosdow A, Kraytsberg G,
Kilpatrick D, Kumar A. Nitrous Oxide Effects on the Expression
of Brain Opiate System, Journal of Dental Research, 71:913A,
March 1992.
239
Jong G, Zive M, Kugel G, Habib C. Surface Treatment Effects on
Porcelain Composite Bonding, Journal of Dental Research,
71:1372, March 1992.
Thomas K, Kugel G, Habib CM. Comparison of Dentin Surfaces
after Treatment with Dentin Bonding Primers Using the
Environmental Scanning Electron Microscope, Journal of Dental
Research, 71:1390, March 1992.
Habib C, Kronman J, Kugel G. One-year Evaluation of
Composite Restoration for Root Surface Caries after ChemoMechanical Excavation, Journal of Dental Research, 71:795,
March 1992.
Kugel G, Achour A, Zive M. A Comparison of Marginal
Microleakage Around Porcelain and Resin Inlay Systems,
Journal of Dental Research, 70:990, April 1991.
Habib C, Kronman J, Kugel G, Tutin, R. Dentinal Bonding and
Composite Restoration of Root Surface Caries after ChemoMechanical Excavation, Journal of Dental Research, 70:1025,
April 1991.
Bellucci A, El Alfy H, Kugel G, Chapman R. Fracture
Resistance of Porcelain Related to Polishing and Glazing.
Journal of Dental Research, 70:638, April 1991.
Latif M, Kugel G, Chapman R, Norris L, Kabani S, Washburn B.
Techniques in Bone Surgery. Journal of Dental Research,
70:1956, April 1991.
Kugel G, Rider C, Angelopoulos A, Fakitsas A. Evaluation of the
Nd:YAG Contact Laser in Oral Surgery. Journal of Dental
Research, 69:1172, March 1990.
Zive MA, Kugel G, Beumer J, Kumar MSA. Brain Neuropeptide
Changes in Rats Exposed to N20, Journal of Dental Research,
69:314, March 1990.
Geshnizgani A, Kugel G, Onderdonk A, Delaney M, McDonough
P, Habib C, Cisneros R. Effect of Nitrous Oxide on Oral
Microorganisms, 89th Annual Meeting, American Society for
Microbiology, May 1989.
Kugel G, Letelier C, Atallah H, Zive M. Chronic Low Level
Nitrous Oxide Exposure and Infertility, Journal of Dental
Research, 68:1057, March 1989.
240
Kugel G, Norris L, Zive M. Nitrous Oxide: Occupational
Exposure, Journal of Dental Research, 68:1058, March 1989.
Kugel G, Letelier C, Atallah H, King JC, Gilmore WC. Nitrous
Oxide and Infertility, Journal of Dental Research, 67:380, March
1988.
Kugel G, Rosenberg L. Effects of Nitrous Oxide Exposure on the
Central Nervous System Control of Reproduction in Female Rats,
Journal of Dental Research, 66:394, March 1987.
King JC, Kugel G, Zahniser D, Wooledge K, Damassa D,
Alexsavich B. Sex Differences in the Response of LHRH Neurons
to Gonadectomy in the Rat: Three-Dimensional Computer
Analyses, Society for Neuroscience, 87, May 1984.
King JC, Lechan RM, Kugel G, Anthony ELP. A Fixative for
Immunocyto-Chemical Localization of Peptides, Greater New
York Dental Meeting, New York, New York, November 1983.
241