SKELETAL FLUOROSIS- AN EPIDIMIO-CLINICO-RADIOLOGICAL STUDY
Dr. Prasanta Kumar Mandal(Asso.Prof)
Dr. Dibakar Ray(Asst.Prof)
Dr. Fagu Ram Majhi(Asst.Prof)
Dr. Somnath Tirkey(Junior Resident)
Dr. Mrinal Kanti Ray(Asst.Prof)
Dr. Surajit Mondal(Junior Resident)
Dept of orthopedics B.S.M.C& H.(Bankura West Bengal India)
Corresponding Address:- drprasantamondal@gmail.com
Abstract
Skeletal fluorosis is endemic problem in may parts of world including India as well as West
Bengal effecting mainly low socio-economic group of populations. This study is to detect the
epidemiological and clinical as well as radiological survey to detect and help to prevent the
morbidity and mortality of the people from the so called slow environmental poison.
Keywords ;- Skeletal Fluorosis, Radiological Study
INTRODUCTION
1
Fluorine is the most abundant element in nature . It occurs naturally in the Earth’s crust,
water and food as the negatively charged ion fluoride (F ). Fluorine is considered to be a trace
element because only small amounts are present in the body (about 2.6 gm in adult), and because
the daily requirement for maintaining health is only a few milligrams a day. About 96% of total
3,5
body fluoride is found in the bones and teeth . Although its role in the prevention of dental
6
caries (tooth decay) is well established , fluoride is not generally considered an essential mineral
element because humans do not require it for growth or to sustain life. However, if one considers
the prevention of chronic diseases (dental caries, osteoporosis), an important criterion in
7
determining essentiality, then fluoride might well be considered an essential trace element .
MATERIALS AND METHODS
The Subject :
The study was carried out on the patients after admission in the department orthopaedics,
Bankura Sammilkani Medical College and Hospital during the year August 2009 to April 2012.
The Case
An exclusive epidemioclinical survey was done in July 2000 in the village-Nashipur of
Birbhum district. The total population including all age groups and sex of the Nashipur village
was covered during the survey. From there, 31 patients chosen by systematic random sampling,
was admitted in the department of orthopaedics and prospective and retrospective study was
done. All skeletal fluorosis cases apparently detected by clinical examination was confirmed by
haematological. Biochemical, radiological and pathological investigations.
The Control
A control village Bhabananidpur 5 km away from Nashipur, having all the matching
characteristics excepting the skeletal fluorosis was considered for the same study also in order to
make valid comparison between the two groups there are sixty patients chosen by systematic
random sampling to isolate the aetiological factors towards the development of the disease.
Therefore at the time of study the following issues was considered :--1. Epidemio-clinical study was case control (Analytical) in nature.
2. Both skeletal and dental fluorosis was detected clinical in initial time.
3. Fluoride content of water in both the villages (i.e. – Nashipur and Bhabanadapur) was
determined by Dept. of Chemistry Burdwan University and that was 12-15 ppm and <.8
ppm respectively.
Thirty one cases of both sex and with all age group of skeletal fluorosis was registered for study.
Each patient was subjected to thorough history and detailed examination with special emphasis
on skeletal system.
A detailed history of duration of exposure or migration, occupation complain of back pain, joint
pain, leg pain, stiffness of spine or any other joints, deformity, breathing difficulty, especially on
excurtion, weakness on limbs was taken.
Each patient was examined thoroughly for any anemia, jaundice, oedema, chest expansion and
mottling.
Thorough examination of spine for kyphosis, tenderness of spinous processes, paraspinal
tenderness, nodule, restriction of movements and also each and every joints of both upper limb
and lower limb examined for deformity, muscular wasting, tenderness and movements.
The diagnosis was confirmed by clinical, biochemical (fluoride level in blood and bone)
radiological and pathological investigations.
The correction of deformity such as genu valgus or genu varus, and preventive measures to
inhibit progression of disease to be taken accordingly.
RESULTS AND ANALYSIS
Present study was conducted on 31 skeletal fluorosis patient and 60 properly matched control
patients.
Table 1: Proportion of patients belonging to different age groups in both sex.
Age in
Sex
Total
Percentage
Years
Male
Female
8-20
5
5
10
32.25
21-30
2
1
3
9.67
31-40
5
2
7
22.58
41-50
4
1
5
16.12
51-60
2
x
2
06.45
61-70
4
x
4
12.90
Age :Youngest patient in this present series was a male aged 8 years and oldest patient in this
series was a male of 70 years. The maximum no. of patient is in between 8-20 years 32.25%.
Average age of the patient was 34.67 years.
Table 2: Sex distribution
Sex
No of Cases
Percentage
Male
22
70.97
Female
9
29.03
In this study group male out numbers females the total percentage for male was 70.97%, and for
female it was 29.03%.
Male : Female ratio is 2.4 : 1
Table 3: Distribution of cases according to their occupation.
Occupation
No of Cases
Percentage
Student
7
22.58
Labourer
14
45.16
Cultivator
4
12.90
Housewife
6
19.35
The table shows that maximum no. of patients (percentage 45.16%) are in the group of labour
and who work outside the home and used to drink more water than the student or housewives.
Table 4: Type of Clinical presentation
Sl. No.
Complaints
No. of Cases
Male
Female
Total
Percentage
1
Back Pain
18
7
25
80.64
2
Joint Pain & leg pain
16
8
24
77.41
3
Stiffness of major joints
14
3
17
54.83
4
Deformity
7
3
10
32.25
5
Neurodeficit
5
X
5
16.12
6
Visible Nodule
12
X
12
38.71
7
Breathing difficulty
14
4
18
58.06
8
Dental fluorosis
11
8
19
61.29
Maximum no (25) of patient (percentage 80.64) complaints of low back pain. Neurodeficit
including quadriplegia is the rarest complain of this study group (only 16.12%).
Table 5: Types of abnormality on General Examination
Sl. No.
Findings
No. of Cases
Percentage
1
Gross Anemia
7
22.58
2
Jaundice
1
03.2
3
Oedema
6
19.35
4
Diminished Chest
expansion (< 3 cm)
31
100
Diminished chest expansion <3 cm is present in 100% cases Jaundice is present minimally in
3.2% cases only.
Table 6: Comparison of chest expansion in case and control.
Sl. No.
No. of cases
Mean (X)
SD
P value
<.001
1
Control
60
5
0.5
2
Case
31
1.92
0.152
Calculation : As this study was done with 31 cases and 60 controle
Case No. ( n 1 ) = 31
Control No ( n 2 ) = 60
So standard error is to be calculated by z value
Z=
SD12 SD 22

n1
n2
5  1.9290
=
=
X1  X 2
0.25 0.023

60
31
3.71
=4.076 from the statistical chart p value is <0.001
0.753
So chest expansion in the case group is significantly reduced than the control group.
Table 7: Abnormalities on regional clinical examinations
Sl.
No.
Region
Abnormalities
No.
of Percentage
patients
1
Spine
Kyphosis
14
45.16
Paraspinal tenderness
18
58.06
Restriction of movements
25
80.64
2
Shoulder
Restricted movement
13
41.93
3
Elbow
Restricted movement
14
45.16
15
48.38
FAD (adduction)
1
3.22
Restriction of movement
16
51.61
(Pronation-supination
Deformity
4
Hip
Fixed flexion deformity
(FFD) ( 100  450 )
5
Knee
Restriction of movt
5
16.12
6
Small
Restriction of movt
joints of
Hands &
feet
6
19.35
3
9.67
5
16.12
Wasting of small muscles
Musculur
Wasting
(Gross)
7
From the above table maximum no of patients 25 (percentage 80.64%) suffering from restricted
spinal movements and restricted knee movement and muscular wasting is minimum (percentage
16.12) in both the situations.
Table 8: Comparative study of fluoride level in blood in case and control group
Sl. No.
Mean X
SD
P Value
<0.001
1
Case ( n 1 -31)
1.315
0.1792
2
Control ( n 2 -60)
0.7
0.075
Fluoride level of blood is significantly high in case group than in control group.
Table 9: Comparative study of fluoride level in bone between case and control.
Sl. No.
Mean
SD
P Value
<0.001
1
Case ( n 1 -31)
5395.51
2707.66
2
Control ( n 2 -60)
750.00
125
Fluoride level of bole in cases is much greater than the control group. The difference is being
statistically significant.
Table 10: Distribution of cases according to X-ray findings
Sl.
No.
X-ray Changes
No. of Cases
Percentage
1
Mild Osteopenia (OP)
7
22.58
2
Osteosclerosis (OS)
24
77.41
3
OS + Diaphyseal widening
(DY)
10
32.25
4
OS + DY + Soft tissue
calcification (Stc)
8
25.8
5
OS + DY + Stc + Osteophyte
6
19.35
The X-ray findings from the above table maximum patients have osteosclerosis. Only six
patients have osteophytic changes (19.35%).
Table 11: Distribution of the patients according to the Grading on the basis of fluoride level of
bone (mg F/kg of ASH concentration)
Sl. No.
Grading
No. of cases
Percentage
1
Preclinical (Pc)
12
38.72
2
II. Clinical phase I (cPI)
8
25.80
3
III Clinical phase II (cP-II)
4
12.90
4
IV Clinical phase III
7
22.58
Discussion
Fluorosis is a clinical condition characterized by mottling of teeth (Dental Fluorosis),
increased density of bone (Skeletal Fluorosis) and it is demonstrated in adult
radiographically and histopathologically due to excess fluoride intake which interferes with
collagen formation in the osteoblasts and chondroblasts (cells that lay down bone and cartilage).
Consumption of excess fluoride results in the body’s inability to discriminate between which
tissues should be mineralised and which tissues should not. In other words, the mineralization of
tissues such as bone (which should be mineralized) is disrupted while tendons, ligaments,
muscles and other soft tissues (which should not be mineralized) start to become mineralized by
interfering with collagen mineralization. Cumulative damage to these cells leads to arthritis,
arteriosclerosis, brittle bones, wrinkled skin, and scleroderma. Fluoride’s disruptive effects on
collagen of soft tissues may also set off other diseases such as muscular dystrophy, rheumatoid
arthritis, lupus etc.
India is among the 23 nations around the globe, where health problems occur due to consumption
of fluoride contaminated water. An estimated 62 million people in India, in 17 out of states are
affected with dental, skeletal and/or non skeletal fluorosis. The extent of fluoride contamination
of water in India varies from 1.0-48 mg/L (A.K. Susheela 1997).
In July 1999 an exclusive door to door epidemiological and clinical survey was done in 12,000
populated village Nashipur of Birbhum District. From that survey we got 620 patient of fluorosis
(Dental, skeletal).
The present study was conducted with 31 patients of both sex and all age group selected by
systemic random sampling from the survey in the village Nashipur of Birbhum district. They
were admitted in the Bankura Medical College and Hospital in the department of orthopaedics.
Sixty patients from the village Bhabanandapur of the same district 5 km away from the
concerned village Nashipur, admitted in the different departments of Bankura Medical College
and Hospital, and Burdwan Medical College and Hospital for some other reasons are taken as a
control group. The information of admission was collected from volunteer appointed from those
villages.
After admission, each and every patient was examined exclusively, detailed history of and
examination findings was written in a proforma.
Name, age, sex, address was taken for their identification, occupation of each and every case was
carefully noted, then chief complain including duration, noted, past history of any major illness
including hospitalization was also noted. Family history including individuals name, age,
affection of dental or skeletal fluorosis was also noted, then personal history including water
consumption, food habit was also noted general survey, including anemia, jaundice, cyanosis,
neck vein, neck glands, decubitus of choice, any visible subcutaneous nodules, oedema, pulse,
respiration blood pressure was also taken carefully.
Detailed examination of back and spine for deformity, swelling, visible nodule, tenderness,
neurodeficit and movements including flexion, extension, lateral bending and rotation noted
carefully.
Each and every joints of upper limb and lower limb examined carefully and noted in the
proforma.
Then patient was investigated for routine blood including TC, DC, ESR Hb% serum bilirubin,
urea, creatinine, serum level of fluoride and fluoride level of bone (taken from biopsy) was
detected. Biopsy specimen also send for histopathological study. X-rays taken from cervical
spine, L.S. Spine, D.L. Spine, Chest, Pelvis, femur including knee, both bone leg including
ankle, shoulder, humerus, including elbow, both bone ferearm including wrist, for skeletal
survey. Diagnosis was confirmed by clinical methods, X-rays, blood and bone level of fluoride,
and histopathological findings.
From the table 1 we can observe that 10 patients (32.25%), 5 male, 5 female are in the age group
of 8-20 years, 3 patients, 2 male, 1 female in the age group of 21-30 years. 7 patients, 5 male, 2
female (22.58%) 5 patients (16.12 %) 4 male, 1 female, 2 patients (6.45%) both males, and 4
patients (12.90%) all males, are in the age group of 31-40 years 41-50 years, 51-60 years and 6170 years respectively. One interesting finding is here there was no female patient in the age
group of 51-60 years and 61-70 years. The youngest patient is 8 years old male oldest patient in
70 years old male with average age of 34.6 years the observation strongly supports the fact that
skeletal fluorosis can involve all the age group starting from first decade as observed by Zipkin
(1959).
From table-2 the sex distribution can be assessed. We can see in our study there were 22 male
patient and 9 female patient. The percentage of males were 70.91 % and that of females were
29.03 %. Male patient out of number than female that was also true in all age group distribution
this may be due to small study sample actual sex distribution in fluorosis patient can only be
assessed by community survey.
Table-3 reveals that maximum no 14 (45.16 %) of patients were labourer by occupation, 4
patients were cultivator (12.90 %), 7 patients were student (22.58%) and 6 patients (19.35 %)
were housewives. From this table it is obvious that persons used to work or stay outside home
(14+4+7)=25, (80.64%) need more water and are more commonly affected. Findings are more or
less matched with observation by SS Jolly 1961.
From table-4 mode of presentation reveals that low back pain is the commonest problem by the
patients. Here we can see maximum 25 (80.64 %) patients complaining of back pain then 24
patients (77.41 %) presented with major joint pain including leg pain, 19 patients (61.29 %) with
mottling, 18 patients (58.06 %) with breathing difficulty on excursion, 17 patients (58.83 %)
with stiffness of major and minor joints, 12 patients (38.71 %) with visible subcutaneous nodule,
10 patients (32.25 %) with genu valgus or genu varus deformity and 5 patients (16.12 %)
presented with neurodeficit including paraparesis, paraplegia, quadriparesis, in order of
frequency. One patient was with bedsores. The cases with deformity (genu varus or genu valgus)
was treated by valgus or varus osteotomy. Out of ten in one case the deformity had recurred in
2.5 years follow up.
These mode of presentation is more or less, similar to findings by S.S. Jolly 1961 and Susheela
AK 1996. Teotia M et. al. – 2000.
Table 5-6 shows hundred percent association with diminished chest expansion which was <3 cm
in comparison to control which was 5 cm with Mean 1.92  0.152 P value <0.001 means
statistically significant. In other words chest expansion is reduced in skeletal fluorosis cases than
the control group which is statistically significant. Findings correlates with previous workers
Sing et. al. 1969. Where are 7 cases (22.58 %) with anemia and only one case of jaundice
(Bilirubin leel is 2 mg/dl) Hemoglobin level were <8 gm% in each. The cause of anemia in cases
was not explained otherwise.
There are 6 cases of oedema feet (19.35 %) which are pitting in type. The cause can not be
explained other wise. The finding correlates with previous workers Mwanil DL et. al. 1994.
Table 7 showing the abnormalities in different joints. From the table it is obvious that spine is the
most common affection. The kyphotic deformity was present in 14 cases (45.16 %), paraspinal
tenderness in 18 patients (58.06 %) and maximum findings restriction of spinal movement in 25
patients (80.64%). All movements was affected, particularly flexion-extension movement. Spinal
movement grossly restricted in 11 cases (35.48 %) of which 5 cases had no movement at all. On
the other hand the spine behaves like a single plate of bone.
Movement was possible but restricted in 13 cases 41.93 % of which 3 cases passive movement
was painful.
In 1 case (3.22 %) the spinal movement was terminally restricted the study findings correlates
with previous investigation Zipkin-1959 Susheela A.K. 1996.
Shoulder movement particularly abduction and external rotation was restricted in 13 cases (41.93
%) of which terminal movement restricted in 6 cases 19.35 %, moderately restricted in 4 cases
(12.9 %). Grossly restricted in 3 cases 9.6 % of which all were painful like frozen shoulder.
In elbow no cases of deformity no tenderness, flexion-extension movements were almost full but
pronation-supination movement was restricted in 14 cases 45.16 % of which 4 cases mildly, 12.9
% 5 cases moderately and 5 cases grossly restricted and painful (16.12 %) respectively.
Similarly restriction of movement of wrist is present only in 3 cases which includes 1
quadriparesis patient. In Hip fixed flexion deformity of variable degree starting from 100 to 450
were present in 15 patients (48.38 %). There was one case of fixed adduction deformity, which
was 200. Not a single case of fracture of hip or shortening of limb was found which is a
contradictory finding to previous investigator Dr. S.J. Jacobson 1990.
The hip movement was restricted to various degree in 16 patients (51.61 %) of which grossly,
moderately and terminally restricted in 5,3 and 8 cases respectively.
There were 10 cases of knee deformity either Genu valgus (6 cases) or genu Varus (4 cases) as
stated earlier. No bony tenderness was found. Restriction of movement was found only in 5
cases, (16.12 %) of which 1 case has no movement possible at all but other 4 cases have
moderate restriction of movement.
In small joints of hands and feet, restriction of movements were found only in 6 patients (19.35
%) wasting of small muscles of hands and feet were found in 3 cases. The findings are
3
corroborative to previous investigator AgarwalND-1969 .
Muscular wasting of hip regions and leg in comparison to control group was found only in 5
9,25
cases (16.12 %). The observation correlates with findings of previous investigator
Witford,
GM - 1996.
From table 8 comparative study of fluoride level of blood in case and control we can see the
mean fluoride level were 1.315 with 0.1792 standard derivation (SD) and 0.7 with 0.075 SD
respectively. As the no of patients n 1 =31 and n 2 =60 both more than 30 standard error should be
calculated from the Z value
Z=
=
X1  X 2
SD12 SD 22

31
60
0.615
= 18.30
0.03359
So P value (from the statistical chart) is <0.001
So in inference it can be said that fluoride level of serum were significantly high in case group
than the control group. Fluoride level in serum was detected by fluoride selective electrode in
Jadavpur University introduced by Frant and Ross (1966) and modified by Jacobson &
3
Weinstien 1977 .
Table 9 shows Mean  SD fluoride level of cases ( n 1 =31) was 5395.51  2707.66 and that of
control ( n 2 =60) was 750  125.
P value < 0.001 the observed difference 4645.51 is more than 30 times the standard error.
So it is at >99% confidence limit. So proven fact is that the bone level of fluoride is much greater
than the control group. The difference is being statistically significant.
Fluoride level was detected from the biopsy specimen taken from the iliac crest or tibia by
fluoride specific electrode in the department of Bioengg. Jadavpur University.
Table 10 shows distribution of cases according to their X-ray findings which shows maximum no
24 (77.41 %) of cases had osteoslcerotic changes. Ten patient (32.25 %) had osteosclerosis with
diaphyseal widening, eight patient (25.8 %) had osteosclerosis with diaphysical widening
associated with soft tissue calcification, 6 patient’s X-ray shows all aforesaid findings along with
osteophytic changes and exostosis like growth in long bones and vertebrate.
Only 7 patient 22.58 % shows osteo penia in their X-rays. The study fundings are more or less
similar to the previous investigator SS Jolly & A Singh 1969 and Watanabe T in 1997. The
paediatric age group patients shows osteopenic changes and diaphysical widening in their radiographs of long bones.
Table 11 reveals maximum no. of patients (no-12 percentage – 38.72 %) were in the preclinical
stage, then 8 patients (25.80 %) 4 patients (12.90 %) and 7 patients (22.58 %) were in the clinical
phase I, clinical phase II and clinical phase III respectively. One interesting observation was that
phases are not in order of frequency as previous investigationr SK Gupta (2000). This difference
not probably due to selection bias of case control study.
The diagnosis was confirmed finally by histopathological examination. All specimen of bone
obtained by biopsy from iliac crest, tibia femur was sent to pathology department. In the
specimen we found distorted Haversian system and irregular laying down of new bone. The
central canals of the mottled systems were enlarged so as to form resorption tunnels. The
2,3
lamellae of mottled osteons were disorderly arranged and irregular . The histopathological
findings are more or less similar in the all of the specimen. The specimens of bone from control
group such changes were not observed in any patient.
SUMMARY AND CONCLUSION
Thirty one patients with all age group and both sexes of skeletal fluorosis selected by systematic
random sampling in an epidemiological survey at Nashipur village of Birbhum district –
admitted in the department of Calcutta National Medical Collges and Hospital Burdwan Medical
College and Hospital were taken for this study. Sixty age, sex socioeconomic status and
geographic location matched persons admitted in different department of Calcutta National
Medical Collges and Hospital Burdwan Medical College and Hospital with different medical
problems were taken as a control group. Fluoride content of drinking water of both the villages
was detected.
Age range of patients were 8-70 years with mean age being 34.67 years. There were 22 male and
9 female patients.
All patients of case group used to drink fluoride toxicated water (12-15 ppm) either since birth or
since 1978.
45.16 % of the patients were manual labour. 80 % of the patients were used to stay outside the
home for working purpose and used to drink more water.
80.64 % patients were complaining of low back pain, 77 % patients had leg pain or major joint
pain, 61.29 % patients had dental fluorosis and 54.83 % patients had great joint stiffness or back
stiffness. Chest expansion was diminished (< 3cm) in 100 % patients, 22.58 % patients had
severe anemia without any other medical cause three (19.35 %) patient had oedema on general
survey chest expansion was significantly reduced 14 patients had kyphotic deformity 25 patients
had restricted spinal movement and 8 patients had paraspinal tenderness. Restricted elbow
movement was found in 14 cases. Fixed flexion deformity of hip was found in 15 cases and
restricted hip movement were found in 16 cases.
Fluoride level of blood and bone was increased significantly. On X-ray 24 patients (77.41 %)
had osteosclerotic changes in their skeleton 22.58 % had mild osteosclerotic. All cases were
histologically fluorotic.
To be more authentic multicentric study with larger number of patients are necessary to know the
nature and extent of the disease and how to handle the problem so that the skeletal fluorosis
patient can be managed in better fashion.
The study group represents only a portion of fluorosis victims of Nashipur village. The affected
villagers have mild to severe skeletal fluorosis. Some of them require symptomatic relief (like
deformity correction). A thorough epidemiological survey of Nashipur and adjacent villages are
necessary to find out the exact magnitude of the problem and a long term follow-up of postoperative patients are required to dictate the efficiency of surgical treatment applied.
All efforts should be given to provide safe drinking water to stop further progress of the disease.
References
1. Park’s text book of Preventive and Social Medicine, K Park 2010 .
2. Text book of orthopaedics and trauma, Kulkarni GS 2009.
3. Fluoride and Human health by WHO-1970
4. Fluoride and Human health by WHO-1984
5. Cerklewski, F.L. Fluoride bioavailability-nutritional and clinical aspects. Nutrition
Research, 1997; Volume 17 : Pages 907-929.
6. Nielson, F.H. Ultratrace minerals. In Sbils, M et. all.. Eds. Nutrition in Health and
disease, 9th edition. Baltimore : Williams & Wilkins, 1999 : Pages 283-303
7. Cerklewski, F.L. Fluoride : essential or just beneficial Nutrition. 1998, Volume 14 :
Pages 475-476
8. Cerklewski, F.L. Fluorine. In O’Dell, B.L. & Sunde, R.A. Eds. Handbook of nutritionally
essential minerals. New York : Marcel Dekker, Inc. 1997 : Pages 583-602
9. Institute of Medicine, Food and nutrition Board Dietary reference intakes : calcium,
Phosphorus, Magnesium, Vitamin D and Fluoride. Washington DC : National academy
press, 1997 : Pages 288-313.
10. Centres for disease control. Achievements in Public Health, 1900-1999 : Fluoridation of
drinking water to prevent dental caries. Morbidity and Mortality Weekly Report
(MMWR). 1999 : Volume 48 : Pages 933-940
11. DePaola, D.P. et. al.. Nutrition in relation to dental medicine. In Sbils, M et. al.. Eds.
Nutrition in health and disease, 9th Edition Baltimore : Williams & Wilkins, 1999 : Pages
1099-1124
12. Krall, E.A. & Dawson. Hughes, B. Osteoporosis In Shils, M et. al.. Eds. Nutrition in
health and disease, 9th Edition Baltimore : Williams & Wilkins, 1999 : Pages 1353-1364
13. Fabinai, L. et. al.. Bone fracture incidence rate in two Italian regions with different
fluoride concentration levels in drinking water. Journal of trace element in medicine &
Biology. 1999. Volume 13 Pages 232-237
14. Lehmann, R. et. al.. drinking water fluoridation : bone mineral density and hip fracture
incidence. Bone. 1998; Volume 22 : Pages 273-278
15. Cesar Libanati, KH, et. al.. Fluoride therapy for osteoporosis. In Moreus, R. et. al.. Eds.
Osteoporosis. San Diego : Academic press, 1996 : Pages 1259-1277
16. Riggs, B.L. et. al.. effect of fluoride treatment on the fracture rate in postmenopausal
women with osteoporosis. The New England Journal of Medicine 1990; Volume 322 :
Pages 802-809.
17. Pak, CY. et. al. Treatment of postmenopausal osteoporosis with slow release sodium
fluoride : Final report of a randomized controlled trial. Annuals of Internal Medicine.
1995; Volume 123 : Pages 401-408
18. Reginster, JY et. al.. The effect of sodium monofluorophosphate plus calcium on
vertebral fracture rate in postmenopausal women with moderate osteoporosis. A
randomized controlled trial. Annuals of Internal Medicine. 1998; Volume 129 : Pages 18.
19. Ringe, J.D. et. al.. Therapy of established postmenopausal osteoporosis with
monofluorophosphate plus calcium : dose-related effects on bone mineral density and
fracture rate. Osteoporosis International 1999; Volume 9 : Pages 171-8.
20. Balena, R. et. al.. Effects of different regiments of sodium fluoride treatment for
osteoporosis on the structure, remodeling and reminerilazation of bone. Osteoporosis
Internal. 1998; Volume 8; pages 428-435
21. Palmer, CA & Anderson, J.J.B. The impact of fluoride on health. Journal of the American
Dietetic Association 2000; Volume 100 : Pages 1208-1213
22. Alexanderson, P. et. al.. Monoflurophosphate combined with hormone replacement
therapy induces a synergistic effect on bone mass dissociating bone formation and
resorption in most menopausal women : a randomized study. The journal of clinic
Endocrinology and Metabolism 1999; Volume 84 : Pages 3013-3020
23. Murray, T.M. & Ste-Marie, L-G. Fluoride therapy for osteoporosis. Canadian Medical
Association Journal (CMAJ). 1996; Volume 155 : Pages 949-954
24. National Research Council. Health effects of ingested fluoride. Washington D.C. :
National Academy Press, 1993
25. Whitford, G.M. The metabolism and toxicity of fluoride. In Meyer, H.H. Ed.
Monographs in oral Science. Volume 13. Basel (Switzerland) : S. Kangen AG, 1996
26. Shortt, H.E. Mc. Robert, G.R. Bannard, T.W. and Mannodinayer, A.S. Indian Med. Res.
1937; 25, 553-561
27. Susheela, A.K. Prevention and control of fluorosis. Vol-II – Health Aspects. Rajiv
Gandhi National drinking water Mission Govt. of India. 1993
28. Susheela, A.K. Kumar, A., Bhatnagar, M. and Bhadur, R., Fluoride, 1993; 26, 97-104
29. Sharma, S. and Bhatnagar, R., UNICEF Report. 1997
30. Susheela, A.K. and Majumdar, K., Guide on water and excreta related disease for
grassroot level functionaries IEC 04. Rajiv Gandhi National Drinking water Mission and
National Institute of Rural Development. Govt. of India. 1998.
31. Paramasivam, R. and Nanoti, M.V. Defluoridation and water quality analysis, National
environmental Engineering Research Institute, Nagpur, 1997
32. Radhakrishna, B.P. Curr. Sci. 1998; 75, 542
33. Gupta, S.K. and Sharma, P., Curr. Sci., 1995, 65, 774
34. Susheela, A.K., Das, Taposh, K., Gupta, I.P. Tandon, R.K. Kacher, S.K., Ghosh, P. and
Deka, R.C. Fluoride, 1992, 25, 5-22.
35. Susheela, A.K. Prevention and control of fluorosis: Technical information for training
cum awareness camp for Doctors, Public Health engineers and other officers, New Delhi,
National Technology Mission of drinking water, 1991
36. World Health Organization. Guidelines for drinking water quality, Geneva, Volumes
World Health Organization, 1984 : p-249
37. Thergoanker VP, Bhanagava RK, water quality and incidence of fluorosis in Jhun-Jhun
District of Rajashthan : Preliminary observation. Indian J Env Hlth 1974; 16 : 168-180
38. Choubisa SL, Sampura K, Bhatt SK, Choubisa DK, Pandya H, Joshi SE, Prevalence of
Flurosis in some villages of Dungarpur District of Rajashthan. Indina J Hlth 1996; 38;
119-126.
39. Public Health Engineering Department Fluoride affected villages. Habitat Survey
Rajashthan, PHED, Rajashthan, Jaipur 1991-93 pp 1-21
40. World Health Organization, Geneva, who Monograph Series No. 59, 1970
41. World Health Organization, Geneva, Fluorine and Fluoride, Geneva, World Health
Organization, 1984; p. 93
42. Jenkins GN, Vankateswarlu P, Zipkin. Physiological effects of small doses of fluoride In
: Fluoride and Human health Geneva. World Health Organization, 1970; pp 163-223
43. Jowsey I, Riggs BL, Kelty PJ. Long term experience with fluoride and fluoride
combination treatment of osteoporosis. In : Calcium Metabolism, Bone and Metabolic
Bone Diseases : Proceedings of the X European Symposium on Calcified Tissues,
Hamburg (Germany), 16-21 Sept. Eds Cordt FK, Kruse HP, Berlin, Springer-Veriag,
1975; pp 151-154
44. Teotia SPS, Teotia M, Singh OP< Bone static and dynamic histomorphometry in
endemic fluorosis In : Fluoride Research 1985 : Studies in environmental science, Vol
27, Amsterdam, Elsevier Science Publisher, 1985; 99 : 347-355.
45. Fuchs C, Dom D, Fuchs CA, Henning HV, Meintosh C, Scheler F. Fluoride
determination. In plasma by ion selective electrode : A simplified method for the clinical
laboratory. Clin Chim Acta 1975; 60 : 157-167.
46. Dean HT. Classification of mottled enamel diagnosis. J Am Dent Assoc 1934; 21 : 14211426
47. Connerty VH, Briggs RA. Determination of serum calcium by means of orthocresopphthalein complexone. Am J Clin Path 1966; 45 : 290-296.
48. Lindoll AW, Ells JE, Roos B. Estimation of biologically active intact parathyroid
hormone in normal and hyperthyroid sero by sequential N-terminal immunaextraction
and midregion radiommunoassay. J Cliin Endo-Crinol Meta 1983; 57 : 1007-1014
49. Armstrong WD, Messer H, Singer L. Effect of bone fluoride on bone resorption and
metabolism. In : Friendrich Kahlan Cordit and Hans peter kruse. Calcium Metabolism,
Bone and metabolic bone disease. Proceedings of the X European Symposium on
Calcified Tissues, Hamburg (German 16-21 Sept. 1973.) Eds. Cord FK, Kruse HP,
Berling, Springer-Veriag, 1975; pp 132-133.
50. Teatia SPs, Teotia M. Hyperactivity of the parathyroid glands in endemic osteoflurosis,
Fluoride, 1972. 5 : 115-126.
51. Gupta SK. Environmental Health perspective of fluorosis in children, Ph. D. Thesis,
University of Rajasthan, Jaipur, Rajasthan, 1999
52. Hotchkiss CE, Broammage R, Du M, Jerome CP. The anesthetic isofurance decreases
ion-ised calcium and increases parathyroid hormone and osteocalcin in cynomolgus
monkeys. Bone 1998; 23 : 479-484.
53. Sribastava RN, Gill DS, Moudgil A, Menon RK, Thomas M, Dandona P. Normal ionized
calcium and increases parathyroid hypersecretion, and elevated osteocalcin in a family
with fluorosis. Metabolism, 1989; 38 : 120-124.
54. Schwartz P. Modsen JC, Rasmussen AG, Transbol IB, Brown EM. Evidence for a role of
intra cellular stored parathyroid hormone in producing hysteresis of the PTH-Calcium
relationship in normal humans. Clini Endo-Crinol 1998; 48 : 725-732.
55. Houlilier P, Blanehard A, Paillard IV. Extra-parathyroid hypercalcemia : Physiopatho logical
and therapeutic : aspects. Ann Med Internne Paris, 1997; 148 : 15-18.