case am teaching point 1 - University of Wisconsin

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OSTEOPOROSIS FOR
THE GENERALIST
DANIEL G. MALONE MD
ASSOCIATE PROFESSOR OF MEDICINE,
RHEUMATOLOGY,
UNIVERSITY OF WISCONSIN, MADISON
[email protected]
LEARNING OBJECTIVES
•RECOGNIZE RISK FACTORS FOR OP AND FOR
FRACTURE
•UNDERSTAND LIMITATIONS OF DEXA SCANNING
•KNOW DIFFERENCES IN MECHANISMS OF ACTION OF
THE ANTI-OP AGENTS
•KNOW WHEN, AND FOR HOW LONG TO TREAT, AND
WHICH DRUGS TO USE
•CHOOSE THE RIGHT DRUG FOR EACH INDIVIDUAL
PATIENT
BALANCE IS HEALTH,
IMBALANCE IS ILLNESS
BONE TURNOVER/
BONE REMODELING
RESORPTIONOSTEOCLASTS
-
BUILDINGOSTEOBLASTS
+
NORMAL BALANCE IN YOUNG ADULT
YOUNG
ADULT
YOUNG
ADULT
RESORPTION
BUILDING
BUILDING=RESPORPTION, SO BONE MASS
AND STRENGTH ARE MAINTAINED
0
0
OSTEOPOROSIS OF AGING/MENOPAUSE
RESORPTION
YOUNG
ADULT
YOUNG
ADULT
BUILDING
RESORPTION HAS INCREASED AND
BUILDING HAS DECREASED, SO BONE
MASS AND STRENGTH DECREASE
0
0
CASE QE
53 YEAR OLD CAUCASIAN WOMAN, IN FOR
ROUTINE YEARLY CHECKUP, NO COMPLAINTS
EXCEPT ONSET OF MENOPAUSAL SYMPTOMS.
NO OTHER MAJOR MEDICAL PROBLEMS, NO OP
RISK FACTORS AND NO HISTORY OF FX. EXAM
NORMAL. SLENDER BODY HABITUS. ALL LABS
FINE…LH AND FSH ELEVATED AT POSTMENOPAUSAL LEVELS, ESTRADIOL 10.
CASE QE
WE DO NOT KNOW EXTENT OF HER RISK
FACTORS EXCEPT SHE IS POST MENOPAUSAL,
CAUCASIAN AND SLENDER. WE DO NOT KNOW
HER GENETICS, OR WHERE ON THE
PROVERBIAL BELL-SHAPED CURVE SHE IS WITH
REGARD TO BONE MASS.
THEREFORE, WE HAVE INSUFFICIENT
INFORMATION ON WHICH TO BASE A THERAPY
DECISION.
MY PRACTICE IS TO GET A FEW BASELINE LABS
AND A BASELINE DEXA.
CASE QE
1. ADVISE INTAKE OF CALCIUM 1500 mg/d,
AND VITAMIN D, DOSE DEPENDENT ON
OUTCOME OF #3.
2. ADVISE EXERCISE OF HER CHOOSING.
3. ORDER DEXA.
4. ORDER 25-OH VITAMIN D LEVEL, CBC,
VITAMIN B12.
5. RE-DO DEXA IN 2-3 YEARS TO
ESTABLISH RATE OF BONE MASS LOSS.
CASE QE
TOTAL 25-OH VITAMIN D <15 ng/ml: CHECK
intact PTH, VITAMIN D3 10,000 IU* PO/day FOR
3 WEEKS, THEN 4000 IU/day FOR 3 WEEKS
THEN RE-CHECK VIT D LEVEL.
TOTAL 25-OH VITAMIN D 16-22 ng/ml: VITAMIN
D3 10,000 IU PO/d FOR TWO WEEKS THEN
4000 IU/d FOR 1 MONTH, THEN RE-CHECK VIT
D LEVEL.
TOTAL 25-OH VITAMIN D 22-29 ng/ml: VITAMIN
D3 2000 UI/d FOR 6 WEEKS, RE-CHECK VIT D.
CASE QE
TARGET FOR TOTAL
25-OH VITAMIN D:
30-60 ng/ml
REMINDER
25-OH VITAMIN D2
+ 25-OH VITAMIN D3
TOTAL 25-OH VITAMIN D
CASE QE TEACHING POINT 1
YOUR MOM WAS RIGHT:
PREVENTION=16 (CURE)
LOSS OF BONE MASS OCCURS RAPIDLY IN THE
FIRST 5-7 YEARS AFTER MENOPAUSE. THEREFORE,
GET DEXA NOW AND IN 2 YEARS. BONE MASS HAS
MANY CONTRIBUTING FACTORS e.g. AGE, GENDER,
HABITUS, LIFESTYLE, GENETICS. RATHER THAN
GUESS AT WHAT HER BONE MASS WILL DO OVER
THE YEARS AFTER MENOPAUSE, MEASURE IT!
FINDING AND CORRECTING BONE MASS LOSS NOW
PREVENTS PROBLEMS IN 20 YEARS!
CASE QE TEACHING POINT 2
HYPOVITAMINOSIS D IS EPIDEMIC! YOU
SHOULD ASSUME YOUR PATIENT’S TOTAL
25-OH VITAMIN D LEVEL IS LESS THAN
DESIRABLE UNTIL PROVEN OTHERWISE.
TREAT TO MAINTAIN AT 30-60 ng/ml
CASE QE TEACHING POINT 3
IF QE IS A MALE, EVERYTHING THE
SAME EXCEPT NO NEED TO ORDER
DEXA UNLESS THERE IS A MAJOR RISK
FACTOR (etoh, hypgonad, steroids,
transplant, etc.)
CASE QE
TEACHING POINT SUMMARY
1. Ca++ 1500 mg/d, VITAMIN D >32ng/ml
2. GET BASELINE DEXA IN FEMALES AT
MENOPAUSE
3. SCREEN MALES ONLY IF MAJOR
RISK FACTOR PRESENT
CASE AF
63 YEAR OLD WOMAN, NEVER HAD ANY
EVALUATION OR RX FOR OSTEOPOROSIS.
16 YRS p MENOPAUSAL. TAKES CALCIUM 1500
mg/d AND VITAMIN D 1000 IU DAILY. NO OTHER
MEDICAL PROBLEMS, NO OP RISK FACTORS AND
NO HISTORY OF FX. IN FOR ROUTINE CHECKUP,
NO COMPLAINTS. EXAM NORMAL. IDEAL BODY
WEIGHT. ALL LABS FINE. TOTAL 25-OH VITAMIN
D 36 ng/ml. DEXA SHOWS T SCORE –1.6 IN SPINE
AND –1.4 IN HIPS.
RX?
CASE AF
BY STRICT CRITERIA, THIS LADY HAS
OSTEOPENIA BY DEXA, BUT SHE HAS NO RISK
FACTORS, NO FRACTURES, AND SHE TAKES
ADEQUATE CALCIUM AND VITAMIN D. NO
FURTHER TREATMENT IS NEEDED AT THIS TIME.
REPEAT DEXA IN 2 OR 3 YEARS TO ESTABLISH
TREND. IF AT THAT TIME SHE SHOWS FURTHER
BMD LOSS, CONSIDER USE OF ANY OF THE
ANTIRESORPTIVE THERAPIES.
CASE AF TEACHING POINT 1
ALL POSTMENOPAUSAL WOMEN
SHOULD TAKE AT LEAST 1500 mg
CALCIUM AND ENOUGH VITAMIN D
TO KEEP TOTAL 25-OH VITAMIN D
LEVEL >30 ng/ml.
REMINDER
25-OH VITAMIN D2
+ 25-OH VITAMIN D3
TOTAL 25-OH VITAMIN D
CASE AF TEACHING POINT 2
OSTEOPOROSIS DEFINITIONS:
GENERAL
OSTEOPOROSIS IS A SKELETAL DISORDER CHARACTERIZED BY
COMPROMISED BONE STRENGTH PREDISPOSING A PERSON TO AN
INCREASED RISK OF FRACTURE. BONE STRENGTH PRIMARILY REFLECTS
THE INTEGRATION OF BONE QUALITY AND BONE DENSITY.1
BY DEXA2
Osteoporosis
-4.0
-3.5
-3.0
-2.5
Low Bone Mass
(Osteopenia)
-2.0
-1.5
Normal
-1.0
- 0.5
T-Score
1. JAMA.2001;285:785-795.
2. Physician’s Guide to Prevention and Treatment of Osteoporosis. Washington, DC: National Osteoporosis Foundation; 2003.
0
+0.5
CASE AF TEACHING POINT 3
RISK FACTORS FOR OSTEOPOROSIS
FEMALE
CAUCASION/ASIAN
POSTMENOPAUSAL
THIN BODY HABITUS
CIGARETTE SMOKING
EXCESSIVE ALCOHOL USE
FAMILY HISTORY OF OSTEOPOROSIS
SEDENTARY LIFESTYLE
CASE AF TEACHING POINT 4
WHEN TO INITIATE THERAPY
HIP T-SCORES < –2.0 NO OP RISK
FACTORS
HIP T-SCORES < –1.5 AT LEAST ONE
OP RISK FACTOR
PRIOR VERTEBRAL OR HIP FRACTURE
1. National Osteoporosis Foundation. Physician's Guide to Prevention and
Treatment of Osteoporosis. Washington, DC: National Osteoporosis
Foundation; 2003:22.
2. J Clin Densitometry. 2002;5:S29-S38.
NOTE: NOT ALL PATIENTS
NEED DRUGS TO TREAT
THEIR BONE MINERAL
ISSUES.
FDA-APPROVED DRUGS FOR
OSTEOPOROSIS IN
POSTMENOPAUSAL WOMEN
FOR PREVENTION:
• BISPHOSPHONATES
– RISEDRONATE
– ALENDRONATE
• ESTROGEN THERAPY
• ESTROGEN+PROGESTIN
THERAPY
• SELECT. ESTR. REC. MOD.
(SERM)
–RALOXIFENE HCL
FOR TREATMENT:
•
•
•
•
BISPHOSPHONATES
TERIPARATIDE
CALCITONIN
SERM
CASE AF TEACHING POINT 5
MONITORING THERAPY BY DEXA
THE MAIN OBJECTIVE OF SERIAL BMD
MEASUREMENTS IS TO IDENTIFY PATIENTS
WITH SIGNIFICANT LOSS IN BMD
IF THE BMD INCREASES OR STAYS THE SAME, NO CHANGE
IN THERAPY IS INDICATED
IF BMD HAS SIGNIFICANTLY DECREASED:
• NONCOMPLIANCE
• ADD A NEW AGENT
• CHANGE TO A DIFFERENT AGENT
International Society for Clinical Densitometry (ISCD)
2002 Position Statement
CASE AF
TEACHING POINT SUMMARY
1. Ca++ 1500 mg/d, VITAMIN D >32ng/ml
2. DEFINITIONS OF OSTEOPOROSIS
AND OSTEOPENIA
3. RISK FACTORS FOR OP
4. WHEN TO TREAT
5. GOALS USING DEXA TO MONITOR
CASE VN
65 Y/O FEMALE SMOKER WHO COMES IN FOR OP
ASSESSMENT BECAUSE HER SISTER TOLD HER
TO. WANTS IBANDRONATE, “BECAUSE IT’S ON
TV.” MOTHER HAD A DOWAGER HUMP, AND WAS
“ALL BENT OVER.” HER SISTER HAD A URI LAST
MONTH, COUGHED, AND FRACTURED 2 RIBS. SHE
WAS DX’D WITH OP BY HER DOC. PATIENT
REPORTS LOSS OF 2 INCHES OF HEIGHT SINCE
HIGH SCHOOL. HAD BILAT THA FOR AVASCULAR
NECROSIS/DJD. REPORTS BACK PAIN, BUT HAS
BEEN TOLD IT IS DUE TO “BAD ARTHRITIS” AND
“BAD DISKS.”
CASE VN
TREATS HER BACK PAIN WITH “A FEW” BRANDIES
PER NIGHT. TAKES VITAMIN D 3000 IU PER DAY
BECAUSE HER SISTER WAS GIVEN THAT DOSE, SO
PT STARTED TOO.
EXAM: YOUR 1ST CRANIAL DETECTS ETOH. PT IS
64” TALL, WEIGHTS 105. HAS DUPUYTREN’S
CONTRACTURES AND TOBACCO STAINS ON NAILS.
TENDER OVER SEVERAL LUMBAR VERTEBRAE.
OTHERWISE EXAM UNREMARKABLE. LABS OK
EXCEPT ALT AND AST MILDLY ELEVATED.
X-RAYS SHOW SEVERE DDD AND DJD OF SPINE
WITH COMPRESSION FX AT T11 AND L1. DEXA: TOO
MUCH SPINE SCLEROSIS FOR INTERPRETATION.
CASE VN TEACHING POINT 1
DEXA IS NOT THE ONLY FACTOR! THERE’S MORE
TO THIS THAN T SCORES
W.H.O. ESTIMATE OF 10 YEAR FRACTURE RISK
WILL INCLUDE SUCH FACTORS AS:
T-SCORE
HX OF FRACTURE
AGE
FAMILY HX
MEDICAL HX
MEDICATIONS
LIFESTYLE
SMOKING
ETOH
GENDER
CASE VN TEACHING POINT 2
THE BEST TREATMENT OPTION FOR
HER DEPENDS ON HER FUTURE RISK
FOR FRACTURE.
REGARDLESS, START VIT D, AND Ca++.
CASE VN TEACHING POINT 2
WE CANNOT ASSESS HER T SCORES, BUT, SHE
HAS ALREADY FRACTURED AT LEAST TWICE,
SO THE BMD READINGS ARE IRRELEVANT, AND
SHE HAS SEVERE OSTEOPOROSIS BY
DEFINITION.
SHE IS AT HUGE RISK FOR FUTURE
FRACTURES. BESIDES, THE DJD LIKELY
WOULD FALSELY ELEVATE THE BMD READING.
ASSOCIATION OF VERTEBRAL
FRACTURES WITH SUBSEQUENT
FRACTURE RISK
# Vertebral Fracture(s)
Fracture Risk
1
Vertebral: 5x increase1, 2
>2
Vertebral: 12x increase1, 2
1 symptomatic
Hip: 2x increase3
1Ross
P.D. et al. Ann. Intern Med 1991;114:919-923
R. et al. JAMA 2001;285:320-323
3Kanis K.A. Osteoporosis and its Consequences, Osteoporosis, Blackwell Science Ltd. p 8
2Lindsay
REMINDER
HALF OF ALL LOW TRAUMA
FRACTURES OCCUR IN WOMEN WHO
DO NOT HAVE OSTEOPOROSIS BY
DEXA CRITERIA.
CASE VN TEACHING POINT 3
DEXA MAY BE MISLEADING IN PATIENTS WITH
HIGH FUTURE FRACTURE RISK, e.g. PATIENTS
WHO HAVE ALREADY FRACTURED, AND/OR
HAVE OTHER RISK FACTORS.
CASE VN TEACHING POINT 4
GIVEN THE WHOLE PICTURE, I
WOULD CHOOSE AN ANABOLIC
AGENT BECAUSE FUTURE
FRACTURE RISK IS SO HIGH.
OSTEOPOROSIS OF AGING/MENOPAUSE
RESORPTION
YOUNG ADULT
YOUNG ADULT
BUILDING
RESORPTION HAS INCREASED AND
BUILDING HAS DECREASED, SO BONE
MASS AND STRENGTH DECREASE
0
0
BISPHOSPHONATES
AND ALL OTHER ANTI-RESORPTIVES
YOUNG
ADULT
YOUNG
ADULT
BUILDING
RESORPTION
DECREASE
NO CHANGE
INHIBIT RESORPTION, SO TIP THE BALANCE
BACK IN FAVOR OF BUILDING, BUT DO NOT
STIMULATE HIGHER LEVEL OF SYNTHESIS
0
0
TERIPARATIDE-FORTEO
BUILDING
INCREASES
MORE THAN
RESORPTION
RESORPTION
INCREASES
STIMULATES BOTH BUILDING AND
RESPORPTION, IN FAVOR OF BUILDING,
SO NET EFFECT IS THAT BONE MASS
AND STRENGTH INCREASE
0
0
BIOCHEMICAL MARKERS OF BONE TURNOVER1
ANABOLIC AGENTS:
TERIPARATIDE
Mean % Change ± SE
ANTI-RESORPTIVE AGENTS:
ALENDRONATE
250
250
P1NP
NTx
200
150
100
50
50
0
0
- 68
- 70
-100
0 1
3
6
Months
1.
150
100
-50
Arch Intern Med. 2005;165:1762-1768.
12
197
200
40
-50
-100
0 1
3
6
Months
12
BONE TURNOVER MARKERS
BONE BUILDUP/OSTEOBLASTIC:
BSAP (bone specific alk phosphatase)
S-OC (serum osteocalcin)
PYRIDINOLINE CROSS LINKS
TYPE 1 COLLAGEN
COLLAGENASE 3
OSTEOPONTIN
BSP (bone sialoprotein)
BONE BREAKDOWN/OSTEOCLASTIC:
P1NP (N-terminal propeptide)
P1CP (C-terminal propeptide)
NTx 1 (crosslinked N-telopeptide of type1 collagen)
CTx 1 (crosslinked C-telopeptide of type1 collagen)
TRAP (tartrate-resistant acid phos)
U-OC (urine osteocalcin)
CATHEPSIN K
CASE VN
TEACHING POINT SUMMARY
1. WHO 10 YEAR RISK FOR FRACTURE
2. CHOICE OF AGENT DEPENDS ON FRACTURE
RISK.
3. DEXA AND T SCORES MAY BE IRRELEVANT
OR MISLEADING IN HIGH RISK PATIENTS
4. ANTI-RESORPTIVE VS ANABOLIC
CASE AM
72 YO CAUCASIAN FEMALE WITH CHRONIC,
UNCHANGED MILD LOW BACK PAIN, AND
KNOWN SEVERE DDD AND DJD OF SPINE, SENT
FOR OP EVALUATION. NO OTHER KNOWN OP
RISK FACTORS, BASELINE LABS ALL NORMAL
INCLUDING TOTAL 25-OH VITAMIN D. TAKES
CALCIUM AND D AS SHE SHOULD. NO OTHER
SIGNIFICANT HX.
CASE AM
DEXA SHOWS T SCORE IN L1-L4 OF
-1.8. HIPS NOT ASSESSED DUE TO
BILATERAL THA.
L1
+1.9
L2
-3.2
L3
-3.8
L4
+1.7
L1-L4
-1.8
WHAT SHOULD YOU DO?
CASE AM
HER T SCORES SUGGEST THAT HER
RISK OF FRACTURE IS NEGLIGIBLE,
SO NO TREATMENT IS NEEDED, AND
I’M DONE, RIGHT?
CASE AM
WRONG. MAJOR DISCREPANCIES AMONGST THE
VERTEBRAE SHOULD RAISE A RED FLAG. THE NEXT
STEP IS TO HAVE A LOOK AT THE DEXA, OR SHOW IT
TO SOMEONE WHO KNOWS HOW TO READ THEM
PROPERLY. YOU DO THIS, AND THE DEXA IMAGES
SHOW SEVERE DDD, DJD, AND A LOT OF BONY
SCLEROSIS. YOU ORDER SPINE FILMS WHICH SHOW
THE DDD AND DJD, BUT ALSO COMPRESSION
FRACTURES AT T11, T12, L1 AND L4.
THE DEXA WAS INCORRECTLY INTERPRETED. SHE IS
AT VERY HIGH RISK FOR ANOTHER FRACTURE AND
NEEDS AGGRESSIVE TREATMENT.
CASE AM TEACHING POINT 1
DEXA IS A GOOD, BUT FAR FROM
PERFECT, TOOL FOR ASSESSING
FRACTURE RISK. ESTIMATED TO
ACCOUNT FOR ONLY ABOUT 25% OF
RISK. NONETHELESS, AT THIS TIME IT
IS THE BEST WE HAVE, AND THERE IS
CORRELATION BETWEEN DEXA
READINGS AND FRACTURE RISK.
DEXA: RELATIONSHIP OF
T-SCORE TO FRACTURE RISK
RATIO
FX RISK RATIO ≈ 2
|T-SCORE|
FOR T-SCORE<0
e.g. IF T-SCORE IS –3, RISK RATIO
FOR FRACTURE IS 2
3
= 8-FOLD
ELEVATED ABOVE NORMAL
DEXA READING IS PROPORTIONAL
TO THE AMOUNT OF X-RAY
ABSORBED BY BONE:
X-RAY BEAM
DETECTOR
THEREFORE DEXA CAN ONLY TELL
US HOW MUCH CALCIUM LIES
BETWEEN THE SOURCE AND THE
DETECTOR—IT CANNOT TELL US
ANYTHING ABOUT HOW THAT
MASS OF CALCIUM IS ARRANGED.
IS CALCIUM ARRANGEMENT
IMPORTANT?
BONE QUALITY, WHICH IS CLOSELY RELATED TO
BONE MICROARCHITECTURE, IS A CRUCIAL
DETERMINANT OF FRACTURE RESISTANCE
1. J Bone Miner Res . 2003;18:1932-1941.
BRIDGE #1
BMD READING = X
X
BLOCKS OF SCRAP IRON LEFT BY WORKERS
BRIDGE #2
BMD READING ALSO = X*
X
*WITHIN THE ERROR OF THE MACHINE
BRIDGE #3
BMD READING ALSO = X
X
DEXA IS UNABLE TO DISTINGUISH BETWEEN THE 3
BRIDGES, YET BRIDGE #3 HAS FAR GREATER STRENGTH
CASE AM TEACHING POINT 1
(REITERATED)
DEXA TELLS YOU NOTHING
ABOUT BONE
MICROARCHITECTURE, AND
THEREFORE ONLY A SMALL PART
OF THE STORY WITH REGARD TO
STRENGTH AND FRACTURE
RESISTANCE!!!
CASE AM TEACHING POINT 2
DEXA ARTIFACTS CAN BE MISLEADING:
DJD OF VERTERAE
VERTEBRAL FRACTURES
SCLEROSIS
CALCIFICATIONS OF AORTA
ROTATION OF PATIENT/SPINE
INCORRECT READING
CASE AM TEACHING POINT
SUMMARY
1. DEXA IS AN IMPERFECT TOOL FOR
FRACTURE RISK ASSESSMENT
2. COMMONLY MISINTERPRETED
3. SUBJECT TO ARTIFACTUAL
ELEVATION OF READINGS-CAN BE
“NORMAL” WHEN PATIENT ACTUALLY
IS AT HIGH FRACTURE RISK
CASE ST
60 Y/O FEMALE WHO COMES IN BECAUSE HER
CXR DONE FOR COUGH SHOWED “WASHED
OUT BONES” IN THE THORACIC SPINE. C/O
FATIGUE AND TINGLING OF FINGERS. H/O FMS
W/ IBS.
MCV=103, HCT 30, VIT D 10, VIT B12 100, PTH
365 (VERY HIGH), ALK PHOS ELEVATED—BONE
FRACTION
OTHER LABS OK.
BMD SHOWS T SCORES –4.0 IN BOTH.
CASE ST
LOW B12 AND VIT D LEVELS WITH MACROCYTIC ANEMIA
STRONGLY SUGGEST MALABSORPTION. PTH IS HIGH
DUE TO VERY LOW VITAMIN D. ELEVATED BONE ALK
PHOS SUGGESTS OSTEOMALACIA, PROBABLY
SECONDARY TO LOW VITAMIN D.
SUSPICION IS THAT THE ”IBS” COULD BE SOMETHING
ELSE!
INITIATE GI WORKUP. LIKELY YOU WILL FIND SPRUE.
TREAT SPRUE, GIVE HIGH DOSE VITAMIN D PO AND
DOCUMENT THAT THE VITAMIN D STAYS AT 60 ng/ml FOR
6 MONTHS, THEN 32-60 THEREAFTER, AND THAT THE
PTH NORMALIZES, INSURE ADEQUATE Ca++ INTAKE.
REEVALUATE BMD IN 1 YEAR.
CASE HL TEACHING POINT 1
SOME CAUSES OF OSTEOPOROSIS
1. GENETIC PREDISPOSITION
2. ORAL STEROIDS FOR LONGER THAN 3 MONTHS
3. MALABSORPTION DISORDERS/POOR NUTRITION
4. HYPERPARATHYROIDISM, 1º, 2º OR 3 º
5. HYPERTHYROIDISM
6. MENOPAUSE + FAILURE TO TREAT
7. INFLAMMATORY ILLNESSES
8. TESTOSTERONE DEFICIENCY IN MALES, ? FEMALES
8. ALCOHOL AND TOBACCO ABUSE
9. INACTIVITY (BEDRIDDEN PATIENTS)
10. DRUGS e.g. CYCLOSPORIN, HEPARIN, ANTICONVULSANTS
CASE HL TEACHING POINT 2
LABS TO BE ACQUIRED BEFORE Rx DECISION
25-OH VIT D--HYPOVITAMINOSIS D, MALABSORPTION
VIT B12--------MALABSORPTION
CBC-------------MALABSORPTION
ESR-------------INFLAMMATORY ILLNESSES, MYELOMA
Ca++ ------------HYPERPARATHYROIDISM
PO4 -------------OSTEOMALACIA
CREATININE-2º/3º HYPERPARATHYROIDISM
ALK PHOS----OSTEOMALACIA, BASELINE
INTACT PTH--HYPERPARATHYROIDISM
8 AM TESTOSTERONE (MALES)- HYPOGONADISM
ALBUMIN------CALCIUM INTERPRETATION
URINE NTx----BASELINE FOR ANTI-RESORPTIVE
CASE ST TEACHING POINT 1
1. OSTEOPOROSIS CAN HAVE ANY OF
SEVERAL UNDERLYING CAUSES.
2. BEFORE DECIDING ON TREATMENT,
IT IS NECESSARY TO DETERMINE IF
THERE IS AN UNDERLYING CAUSE
OF THE OSTEOPOROSIS, BECAUSE
IF MISSED, THERAPY FOR
OSTEOPOROSIS WILL PROBABLY
FAIL.
CASE ST TEACHING POINT 2
LOW VITAMIN D RESULTS IN ELEVATION
OF PTH, AND IF SUFFICIENTLY SEVERE
AND PROLONGED, IN ELEVATION OF
ALKALINE PHOSPHATASE, INDICATING
OSTEOMALACIA.
CASE ST TEACHING POINT 3
CORRECTION OF HYPOVITAMINOSIS D
SHOULD BE DONE IMMEDIATELY, BUT
RETURN OF PTH AND ALK PHOS TO
NORMAL MAY TAKE MONTHS.
CASE ST TEACHING POINT 4
IN CASES OF SEVERE HYPOVITAMINOSIS D AND OSTEOMALACIA,
IT IS ESSENTIAL TO INSURE
ADEQUATE CALCIUM INTAKE DURING
TREATMENT!---YOU NEED BRICKS TO
BUILD HE WALL.
CASE ST
TEACHING POINT SUMMARY
1. ID UNDERLYING CAUSES OF OP
2. EFFECTS OF HYPOVITAMINOSIS D
3. PTH AND ALK PHOS NORMALIZATION MAY TAKE MONTHS
4. INSURE ADEQUATE CALCIUM INTAKE
CASE ML
55 YO FEMALE 6 YEARS POST MENOPAUSAL HAS BEEN STABLE
ON IV BISPHOSPHONATE FOR 3 YEARS. COMES IN HORRIFIED,
AND WANTS TO STOP ALL OSTEOPOROSIS TREATMENT,
BECAUSE “I HAVE A TOOTH THAT NEEDS TO BE REPAIRED, AND
WHEN HE DOES IT, ALL MY TEETH ARE GOING TO FALL OUT AND
I WILL BE IN HORRIBLE PAIN.”
SHE READ IN COSMOPOLITAN THAT THERE IS A TERRIBLE
DENTAL PROBLEM WITH OP DRUGS, AND THAT ALL WOMEN
SHOULD IMMEDIATELY SEE THEIR DOCTORS ABOUT IT BEFORE
THEIR HEADS FALL OFF.
CASE ML
REASSURE HER THAT THIS IS LARGELY
MEDIA HYSTERIA. “ONJ” OF THE JAW IS
QUITE RARE, IS NOT ACTUALLY
“AVASCULAR NECROSIS” OR EVEN
“NECROSIS” FOR THAT MATTER.
CASE ML TEACHING POINT 1
THE MYTHOLOGY AND HYSTERIA OF ONJ:
SO-CALLED “OSTEONECROSIS OF THE JAW” IS
DEFINED IN THE DENTAL LITERATURE AS AN EXPOSED
AREA OF BONE IN THE MOUTH THAT DOES NOT HEAL
AFTER 8 WEEKS.
DESCRIBED IN PATIENTS WITH HYPERCALCEMIA OF
MALIGNANCY WHO WERE RECEIVING FREQUENT
TREATMENT WITH IV BISPHOSPHONATES TO LOWER
SERUM CALCIUM. DOSES ROUGHLY TENFOLD ABOVE
USUAL OP DOSES.
THE HISTOLOGY IS COMPLETELY DIFFERENT THAN
THAT OF AVASCULAR NECROSIS.
CASE ML TEACHING POINT 1
THE MYTHOLOGY AND HYSTERIA OF ONJ:
•IN FACT, THE HISTOLOGY OF THE ONJ LESION BEARS NO
RESEMBLANCE TO AVASCULAR NECROSIS, RATHER, IT IS
INDISTINGUISHABLE FROM OSTEOMYELITIS, BUT THERE
IS NO EVIDENCE OF INFECTION.
•MOST PATIENTS HAVE LITTLE OR NO PAIN.
•THERE IS ABSOLUTELY NO RELIABLE EVIDENCE THAT
CESSATION OF BISPHOSPHONATES PRIOR TO DENTAL
PROCEDURES IS IN ANY WAY PREVENTATIVE OR
BENEFICIAL. NONETHELESS, TO KEEP THE LAWYERS AT
BAY, THE ADA HAS RECOMMENDED POSTPONEMENT OF
PROCEDURES UNTIL PATIENTS ARE OFF DRUG FOR
SEVERAL WEEKS.
CASE ML TEACHING POINT 1
THE MYTHOLOGY AND HYSTERIA OF ONJ:
•MOST OF THE CONCERN ABOUT THIS IS
UNFOUNDED, SINCE THE LESION IS EXTREMELY
RARE.
•WELL OVER 90% OF CASES HAVE BEEN
DESCRIBED IN CANCER PATIENTS ON
CHEMOTHERAPY.
•NO PREDISPOSING FACTOR HAS BEEN
IDENTIFIED, EXCEPT THAT IN SOME CASES
LESIONS OCCUR AT SITES OF RECENT DENTAL
PROCEDURES.
THE RISK OF DEATH FROM MANY THINGS IS
MUCH HIGHER THAN THE RISK OF ONJ !
1216
Risk/100,000 people/year
20
15
10
5
0
MVA
www.ncs.org/lrs/statinfo/odds.htm
Murder Drowning
Fire
ONJ
Neugut, et. al., Arch Int Med, 2001 15-21
Penicillin
CASE QW
62 Y/O FEMALE W/O COMPLAINT. SENT FOR EVAL OF OP
THERAPY. MENOPAUSE AGE 53, PUT ON HRT THEN,
AND TOOK IT UNTIL 1 YR AGO. QUIT BECAUSE OF
ADVERSE PUBLICITY.
HAD BMD STUDY AGE 56 THAT WAS NML. REPEAT
STUDY AGE 61 ALSO OK. BMD DONE THIS MONTH
SHOWS LOSS OF BONE DENSITY IN VERTEBRAL AND
FEMORAL HEAD. T SCORES –1.9.
ALL LABS NORMAL. NO UNDERLYING CAUSE FOR
OSTEOPOROSIS.
?THERAPY?
CASE QW
BECAUSE HRT MAINTAINED HER
BMD QUITE NICELY FOR 8 YEARS, A
S.E.R.M. (e.g. RALOXIFENE) IS
PROBABLY ADEQUATE, ALONG WITH
Ca++ AND VIT D.
TREAT FOR 2 YEARS AND REPEAT
BMD.
CASE QW TEACHING POINT 1
NOT EVERY PATIENT NEEDS
BISPHOSPHONATES, FOR MANY
PATIENTS THE SERMS WORK FINE.
DO NOT USE IN PATIENTS WITH HX OF
CLOTS.
CASE QW TEACHING POINT 2
DEXA SHOULD BE DONE EVERY TWO OR
THREE YEARS WHEN MONITORING A
NEW THERAPY. LEAST SIGNIFICANT
CHANGE IN DEXA CANNOT OCCUR
FASTER THAN THAT USING ANTIRESORPTIVE DRUGS.
CASE QW
TEACHING POINT SUMMARY
1. THERE AE ALTERNATIVES TO
BISPHOSPHONATES.
2. DO DEXA SCANS q 2-3 YEARS TO
MONITOR RX WITH ANTI-RESORPTIVES.
CASE JG
70 Y/O CAUCASIAN WOMAN NEVER HAD A
BMD OR ANY SORT OF OP THERAPY.
+FAMILY HX OF OP. NO FRACTURE HX.
MENOPAUSE AGE 49.
ALL LABS NORMAL, EXCEPT TOTAL 25-OH
VITAMIN D 20 ng/ml. BMD SHOWS T
SCORES OF –2.5 IN VERTEBRAE AND
FEMUR.
?THERAPY?
CASE JG
SHE HAS OSTEOPOROSIS, ALSO
HAS A RISK FACTOR OR TWO, SO
NEEDS TREATMENT. START VIT D3
2000 IU/d AND Ca++ 1500 mg/d, AND
BISPHOSPHONATE OR SERM. YOU
CHOOSE A BISPHOSPHONATE.
RE-MEASURE TOTAL 25-OH VIT D IN
3 MONTHS, AND BMD IN 2 YEARS
CASE JG TEACHING POINT 1
RISK FACTORS FOR OSTEOPOROSIS
FEMALE
CAUCASIAN/ASIAN
POSTMENOPAUSAL
THIN BODY HABITUS
CIGARETTE SMOKING
EXCESSIVE ALCOHOL USE
FAMILY HISTORY OF OSTEOPOROSIS
SEDENTARY LIFESTYLE
CASE JG
3 MONTHS LATER, TOTAL 25-OH
VITAMIN D IS 24 ng/ml. SHE IS
RELIABLE AND YOU BELIEVE HER
THAT SHE TAKES THE VITAMIN D,
2000 IU/d, AS PRESCRIBED.
CASE JG
INCREASE VITAMIN D3 DOSE TO
3000 IU/d AND CHECK IT AGAIN IN 2
MONTHS. ADJUST DOSE TO
MAINTAIN TOTAL 25-OH VITAMIN D
LEVEL AT 32-50 ng/ml.
CASE JG TEACHING POINT 2
THE CORRECT DOSE OF VITAMIN D IS
THAT DOSE THAT MAINTAINS THE TOTAL
25-OH VITAMIN D LEVEL IN THE RANGE
32-55 ng/ml.
CASE JG
SHE RETURNS 2 YEARS LATER,
AND REPEAT DEXA SHOWS SOME
IMPROVEMENT. SHE CAN NO
LONGER TOLERATE ANY OF THE
ORAL BISPHOSPHONATES DUE TO
GERD. SAYS SHE FORGETS TO
TAKE MED SOME WEEKS.
NOW WHAT?
CASE JG
BISPHOSPHONATES HAVE WORKED
FOR HER, THUS YOU WANT TO
CONTINUE HER ON THAT CLASS OF
DRUG.
SWITCH TO AN IV BISPHOSPHONATE.
CASE JG TEACHING POINT 3
IV BISPHOSPHONATES:
•IBANDRONATE (BONIVA)
q 3 MO.
•PAMIDRONATE (AREDIA)
q 3 MO.
•ZOLEDRONATE (RECLAST)
1/yr
CASE JG
TEACHING POINT SUMMARY
1. USE IV BISPHOSPHONATES IN
PATIENTS INTOLERANT TO
ORALS.
2. KEEP TOTAL 25-OH VITAMIN D
32-60 ng/ml
3. DIFFERENT SCHEDULES FOR IV
BISPHOSPHONATES
CASE CP
77 YEAR OLD ASYMPTOMATIC ACTIVE
FEMALE WITH OSTEOPOROSIS. ON
ORAL BISPHOSPHONATE FOR 8 YEARS.
BMD READINGS STABLE AT -2.6 IN HIPS
AND SPINE. LABS ALL OK. THIS YEAR’S
DEXA UNCHANGED. NO HX FRACTURE.
TOTAL 25-OH VITAMIN D LEVEL 44 ng/ml.
CASE CP
WHILE DATA ON THIS ISSUE ARE NOT
ABUNDANT, RECENT STUDIES SUGGEST THAT
A “DRUG HOLIDAY” IS IN ORDER. THIS MEANS
STOPPING THE BISPHOSPHONATE FOR TWO
YEARS. CONTINUE CALCIUM AND VITAMIN D
AS BEFORE.
CASE MA
77 YEAR OLD ASYMPTOMATIC ACTIVE FEMALE
WITH OSTEOPOROSIS. ON ORAL
BISPHOSPHONATE FOR 6 YEARS. BMD
READINGS STABLE AT -3.0 IN HIPS AND SPINE.
LABS ALL OK. TRIPPED ON RUG IN HOME AND
FELL AGAINST A WALL, USING HER WRIST TO
CUSHION THE IMPACT. SUSTAINS FX OF WRIST.
CXR SHOWS COMPRESSION FX OF T12. THIS
FX WAS NOT THERE ON CXR 4 YEARS AGO.
CASE MA
SHE HAS 2 LOW TRAUMA FRACTURES
WHILE TAKING A BISPHOSPHONATE FOR
6 YEARS. SHE HAS NO SECONDARY
CAUSE FOR OP, AND HER FUTURE FX
RISK IS VERY HIGH. STOP
BISPHOSPHONATE, START
TERIPARATIDE, CONTINUE VITAMIN D
AND CALCIUM AS BEFORE.
CASE MA
PATIENT WHINES ABOUT GIVING HERSELF SHOTS,
WORRIED THAT IT WILL HURT AND THAT SHE
CANNOT DO IT. AFRAID HER INSURANCE
COMPANY WILL NOT PAY FOR IT, EVEN THOUGH
SHE HAS GOOD DRUG COVERAGE.
CASE MA
EXPLAIN THAT THE SHOTS ARE REALLY EASY TO
DO, THE NEEDLE STAYS QUITE SUPERFICIAL, AND
DOES NOT GO INTO MUSCLE OR VEINS, BECAUSE
THE NEEDLE IS VERY SHORT AND VERY FINE (31 G)
AND CAN BARELY BE FELT.
FURTHERMORE, MILLIONS OF DIABETICS OF ALL
AGES, ALL OVER THE WORLD, GIVE THEMSELVES
IDENTICAL SUB Q. SHOTS WITH THE IDENTICAL
EQUIPMENT, SEVERAL TIMES A DAY.
CASE MA TEACHING POINT 1
PATIENTS WHO FRACTURE, OR WHO CONTINUE TO
LOSE BONE MINERAL BY DEXA WHILE ON A
BISPHOSPHONATE OR SERM, ARE CANDIDATES
FOR AN ANABOLIC AGENT. TERIPARATIDE IS THE
ONLY ONE AVAILABLE IN THE USA AT PRESENT.
FOR THESE HIGH RISK PATIENTS, DO NOT BE
AFRAID TO PRESCRIBE IT, OR TO REFER TO OP
CLINIC. LAB MONITORING IS NOT NECESSARY AND
SIDE EFFECTS ARE MINIMAL/ABSENT.
ANOTHER ANABOLIC AGENT, ORAL STRONTIUM
RANELATE, IS USED IN EUROPE AND ASIA, AND
SOMEDAY MAY COME TO A PHARMACY NEAR YOU.
CASE MA TEACHING POINT 2
PATIENTS’ PERCEPTION OF THE DOWNSIDE OF
TERIPARATIDE USUALLY IS FAR WORSE THAN
REALITY:
SUB CUT INJECTIONS-THE PRE-LOADED SYRINGE IS EASY TO
USE, AND ALMOST ALL PATIENTS LEARN THE TECHNIQUE
QUICKLY AND HAVE NO PROBLEM GIVING THEMSELVES THE
MEDICATION. FREE TRAINING SESSIONS ARE AVAILABLE FROM
MANUFACTURER, IN THE PATIENT’S HOME IF NECESSARY. 30
GAUGE NEEDLES ARE NEARLY PAINLESS.
COST-BENEFITS OUTWEIGH THE HIGH COST BECAUSE
TERIPARATIDE CANDIDATES HAVE THE HIGHEST RISK FOR
FUTURE FX. CO-PAY AND FINANCIAL ASSISTANCE ARE AVAILABLE
FROM THE MANUFACTURER FOR PATIENTS WHO QUALIFY.
INSURANCE COMPANIES NO LONGER GIVE DOCTORS PROBLEMS
WITH APPROVAL EXCEPT WHEN THE PATIENT APPEARS NOT TO
BE A CANDIDATE FOR TERIPARATIDE.
CASE MA TEACHING POINT
SUMMARY
1. TERIPARATIDE IS A USEFUL AND EFFECTIVE
AGENT, AND SHOULD BE PRESCRIBED FOR THE
HIGHEST RISK PATIENTS, OR THOSE WHO FAIL,
OR WHO CANNOT TOLERATE BISPHOSPHONATES.
2. PATIENT MAY NEED TO BE RE-ASSURED
REGARDING ITS USE. MOST HAVE NO TROUBLE
WITH IT.
3. DOCTOR NEED NOT MONITOR LABS-RELATIVELY
EASY TO PRESCRIBE. EASE OF USE FAVORABLE,
SIDE EFFECTS LOW, COST HIGH.
CASE TP
63 Y/O MALE COMPLAINING OF FATIGUE,
GENERALIZED MYALGIA, ARTHRALGIA IN
SHOULDER AND HIP GIRDLE REGIONS.
ONSET A FEW WEEKS AGO. NO OTHER
COMPLAINTS. EXAM UNREMARKABLE.
NO OP RISK FACTORS. ESR 55, OTHER
LABS ALL NORMAL, INCLUDING B 12, 25OH VIT D AND TESTOSTERONE.
CASE TP
REMEMBERING YOUR EXTENSIVE
RHEUMATOLOGY ROTATIONS DURING
RESIDENCY, YOU DIAGNOSE PMR AND GIVE
PREDNISONE 15 mg/day. 3 DAYS LATER HE
RETURNS SINGING YOUR PRAISES, BECAUSE
ALL OF HIS SYMPTOMS VANISHED 12 HOURS
AFTER THE FIRST PREDNISONE DOSE. HE
CONSIDERS YOU A DEITY. YOU THANK HIM
AND SEND HIM HOME WITH THE USUAL
TAPERING AND ESR SCHEDULE.
CASE TP
NICE WORK DOC, GOOD DIAGNOSIS AND
TREATMENT PLAN.
HOWEVER, YOU LOST YOUR DEITY
STATUS BY FAILING TO GET DEXA AND
STARTING HIM ON A BISPHOSPHONATE.
CASE TP TEACHING POINT 1
STEROID-INDUCED BONE LOSS OCCURS
RAPIDLY AND EARLY IN THE TREATMENT
COURSE, THUS IF HE IS TO BE ON
STEROIDS LONGER THAN 3 MONTHS (very
likely with PMR), YOU NEED TO ADDRESS
THIS ISSUE. YOU NEED BASELINE DEXA
PLUS A BISPHOSPHONATE.
CASE TP TEACHING POINT 2
STEROIDS CAUSE THINNING, BUT NOT
BREAKING OF TRABECULAE, SO BONE
MASS LOSS DUE TO STEROIDS IS MORE
RAPIDLY REVERSIBLE THAN THAT FROM
AGE-RELATED OP.
CASE TP TEACHING POINT 3
IF BONE MASS CONTINUES TO DECREASE
DESPITE USE OF BISPHOSPHONATE OR
PATIENT CANNOT TOLERATE ORAL OR IV
BISPHOSPHONATE, SWITCH TO
TERIPARATIDE, AS IT HAS BEEN SHOWN
SUPERIOR (BMD AND FRACTURE
REDUCTION) TO BISPHOSPHONATES IN
STEROID INDUCED OP1.
1K.
SAAG ET AL. ASBMR MEETING 2007
CASE TP TEACHING POINT
SUMMARY
1. PRESCRIBE BISPHOSPHONATE FOR ANY
PATIENT WHO YOU THINK WILL BE ON
STEROIDS LONGER THAN 3 MONTHS.
2. STEROID-INDUCED TRABECULAR
CHANGES EASIER TO REVERSE THAN
AGE/HORMONAL-INDUCED CHANGES.
3. USE TERIPARATIDE IF PT INTOLERANT OF
BISPHOSPHONATES, OR
BISPHOSPHONATES FAIL (supporting data
exist)
CASE FA
53 Y/O MALE WITH ALPHA-1 ANTITRYPSIN DEFICIENCY. ON LUNG XPLANT
LIST. OTHERWISE GOOD HEALTH. NO
H/O FX. NEVER TOOK STEROIDS.
FINALLY ADMITS TO BEING AN
ALCOHOLIC. BMD SHOWS T SCORE OF –
3.1 IN VERTEBRAE AND –2.7 IN HIPS.
LABS UNREMARKABLE.
CASE FA
HE ALREADY HAS OSTEOPOROSIS &
DEXA SHOWS AN 8-FOLD INCREASED
FRACTURE RISK. IN THE NEAR FUTURE
HE WILL START LONG-TERM STEROIDS
AND CYCLOSPORIN FOR REJECTION
SUPPRESSION. THESE DRUGS WILL
ACCELERATE LOSS OF BONE MINERAL.
STOP ALCOHOL, START TERIPARATIDE,
VIT D AND Ca++ NOW, BEFORE XPLANT.
CASE FA TEACHING POINT 1
ALCOHOL CESSATION IS CRUCIAL,
BECAUSE WITH CONTINUED ALCOHOL
ABUSE NO THERAPY WILL WORK.
CASE FA TEACHING POINT 2
TERIPARATIDE IS PROBABLY THE BEST
AGENT IN THIS CASE, AS IT HAS BEEN
SHOWN IN TO BE SUPERIOR (BMD and
FRACTURE PREVENTION) FOR STEROIDINDUCED OP.
CITE ASBMR ABSTRACT OR
PUBLISHED ARTICLE
CASE FA
PATIENT QUITS ETOH AND GOES ON
TERIPARATIDE. YOU RE-DO DEXA 1
YEAR LATER. IT SHOWS INCREASE IN
VERTEBRAE BMD OF 20% AND IN HIP OF
12%. CONTINUE TERIPARATIDE FOR
ANOTHER YEAR, THEN OFFER
BISPHOSPHONATE.
CASE FA TEACHING
POINT SUMMARY
1. REMOVE UNDERLYING CAUSES
2. AFTER TERIPARATIDE, MAINTAIN
MINERAL CONTENT WITH ANTIRESORPTIVE AGENT.
CASE EC
80 Y/O FEMALE WHO DOES NOT BELIEVE IN
DOCTORS BECAUSE “NONE OF ‘EM KNOW
NOTHIN’.” PROUD OF THE FACT THAT SHE
HAS NOT BEEN TO A DOCTOR IN 45 YEARS,
WHEN SHE GAVE BIRTH TO HER YOUNGEST
DAUGHTER, WHO NOW DRAGS HER IN TO SEE
YOU. THE TWO OLDER DAUGHTERS HAVE OP
AND THE THREE DAUGHTERS CONSPIRED TO
GET MOM WORKED UP FOR IT AS WELL.
CASE EC
DEXA SCAN, WHICH IS PROPERLY DONE AND
READ, SHOWS T-SCORES OF -4.5 IN HIPS AND
VERTEBRAE. TOTAL 25-OH VITAMIN D 8 ng/ml,
Ca++ 9.4 (9.4-10.3). PATIENT ANXIOUS TO GET
BACK TO HER MILKING AND FIELD WORK ON
TRACTORS, AND HER DANCING. SHE TAKES
NO MEDS.
“I FEEL GREAT, DO YOU KNOW WHAT YOU’RE
DOIN’?”
CASE EC
DUE TO HER T-SCORES AND HER LIFE STYLE HER
RISK FOR FRACTURE IS VERY HIGH. SHE IS A
TERIPARATIDE CANDIDATE. YOU TALK UNTIL
ONSET OF CYANOSIS (your face-not hers), BUT YOU
CANNOT CONVINCE HER TO TAKE IT.
“ONLY NURSES SHOULD GIVE SHOTS, AND I AIN’T
NO NURSE, SO I AIN’T TAKIN’ NO SHOTS.”
YOU INFORM HER THAT THE NEXT BEST
TREATMENT IS A BISPHOSPHONATE, SO YOU
DISCUSS WITH HER BISPHOSPHONATE OPTIONS.
CASE EC
“SONNY, YOU MUST BE NUTS IF YOU THINK I’M
TAKIN’ SOME PILL ONCE A WEEK THAT’S GONNA
GIVE ME AN UPSET STOMACH, AND I CANT HAVE
MY MORNING COFFEE BEFORE I TAKE IT OR FOR
AN HOUR AFTER, AND I CAN’T LIE DOWN!
BESIDES, THIS DRUG AIN’T GONNA DO NO GOOD IF
I ONLY TAKE IT ONCE A WEEK. FORGIT IT.”
CASE EC
YOU REMIND HER THAT SHE CAN GET A
BISPHOSPHONATE IV. FINALLY SHE
CONSENTS TO GET ZOLEDRONATE 5 mg IV
ONCE A YEAR.
“OK SONNY. I CAN DO 15 MINUTES ONCE A
YEAR. IT’S PROBABLY STRONG ENOUGH
BECAUSE I GET IT RIGHT INTO MY BLOOD.
SEE, I TOLD YOU ONLY NURSES SHOULD BE
GIVIN’ THIS STUFF!”
CASE EC TEACHING POINT 1
AVAILABLE BISPHOSPHONATES:
RISEDRONATE (ACTONEL)
ALENDRONATE (FOSAMAX AND GENERICS)
TILUDRONATE (SKELID)
ZOLEDRONATE (RECLAST)
IBANDRONATE (BONIVA)
PAMIDRONATE (AREDIA)
ETIDRONATE (DIDRONEL)
CASE EC TEACHING POINT 2
IV BISPHOSPHONATES ARE AN
ATTRACTIVE ALTERNATIVE TO ORAL
BISPHOSPHONATES.
•COMPLIANCE ASSURED
•PATIENT CONVENIENCE
•NO GI SIDE EFFECTS
•NO ABSORPTION PROBLEMS
•HOWEVER, MORE EXPENSIVE
CASE EC
YOU HAVE OPTIONS GIVING IT:
1. GIVE IT IN YOUR OFFICE OR CLINIC
2. SEND HER TO OSTEOPOROSIS CLINIC
3. SEND HER TO THE INFUSION CENTER
YOU CHOOSE YOUR OFFICE, SINCE “THEM GUYS IN
OP CLINIC DON’T KNOW NOTHIN’ EITHER.”
CASE EC
THE INFUSION GOES WELL. YOU
GET A CALL 4 HOURS LATER. SHE IS
IN THE ER WITH DIFFUSE
CRAMPING, AN ABNORMAL ECG,
AND CHVOSTEK’S SIGN. SERUM
CALCIUM IS 7.0. PATIENT IS NOT
PLEASED. REITERATES HER
OPINION ABOUT DOCTORS.
WHAT HAPPENED?
CASE EC TEACHING POINT 3
ALWAYS CHECK CREATININE,
TOTAL 25-OH VITAMIN D AND
CALCIUM PRIOR TO GIVING IV
BISPHOSPHONATE!
THE PATIENT BECAME PROFOUNDLY
HYPOCALCEMIC BECAUSE YOU GAVE HER
A POTENT BISPHOSPHONATE WITHOUT
CORRECTING HER LOW VITAMIN D AND
BORDERLINE LOW CALCIUM
CASE EC TEACHING POINT
SUMMARY
1. DISCUSS ALL BISPHOSPHONATES WITH
PATIENT-ORAL AND IV.
2. IV A GOOD ALTERNATIVE TO ORAL, AND
THERE IS NO REASON TO PREFER ORAL
OVER IV AGENTS
3. NEVER GIVE IV BISPHOSPHONATE UNTIL
TOTAL 25-OH VITAMIN D IS
NORMALIZED, CALCIUM INTAKE
OPTIMIZED AND CrCl BETTER THAN 25.
CASE HL
45 YEAR OLD MALE SMOKER C/O SEVERAL YEARS
OF LOW ENERGY, FATIGUE, LOSS OF STRENGTH,
GENERAL MALAISE, DEPRESSION, LOW LIBIDO. NO
HX OF OTHER MEDICAL PROBLEMS. IS HERE
BECAUSE HIS PRIMARY DID A CHEST FILM AND
RADIOLOGIST NOTED OSTEOPENIA OF THORACIC
SPINE.
EXAM: GYNECOMASTIA, SPARSE BEARD GROWTH.
DEXA: -3.8 IN SPINE AND HIPS. WHAT NEXT?
CASE HL
1. OSTEOPOROSIS CAN HAVE ANY OF
SEVERAL UNDERLYING CAUSES.
2. BEFORE DECIDING ON TREATMENT,
IT IS NECESSARY TO DETERMINE IF
THERE IS AN UNDERLYING CAUSE
OF THE OSTEOPOROSIS, BECAUSE
IF MISSED, THERAPY FOR
OSTEOPOROSIS WILL PROBABLY
FAIL.
CASE HL TEACHING POINT 1
SOME CAUSES OF OSTEOPOROSIS
1. GENETIC PREDISPOSITION
2. ORAL STEROIDS FOR LONGER THAN 3 MONTHS
3. MALABSORPTION DISORDERS/POOR NUTRITION
4. HYPERPARATHYROIDISM, 1º, 2º OR 3 º
5. HYPERTHYROIDISM
6. MENOPAUSE + FAILURE TO TREAT
7. INFLAMMATORY ILLNESSES
8. TESTOSTERONE DEFICIENCY IN MALES, ? FEMALES
8. ALCOHOL AND TOBACCO ABUSE
9. INACTIVITY (BEDRIDDEN PATIENTS)
10. DRUGS e.g. CYCLOSPORIN, HEPARIN, ANTICONVULSANTS
CASE HL TEACHING POINT 2
LABS TO BE ACQUIRED BEFORE Rx DECISION
25-OH VIT D--HYPOVITAMINOSIS D, MALABSORPTION
VIT B12--------MALABSORPTION
CBC-------------MALABSORPTION
ESR-------------INFLAMMATORY ILLNESSES, MYELOMA
Ca++ ------------HYPERPARATHYROIDISM
PO4 -------------OSTEOMALACIA
CREATININE-2º/3º HYPERPARATHYROIDISM
ALK PHOS----OSTEOMALACIA, BASELINE
INTACT PTH--HYPERPARATHYROIDISM
8 AM TESTOSTERONE (MALES)- HYPOGONADISM
ALBUMIN------CALCIUM INTERPRETATION
URINE NTx----BASELINE FOR ANTI-RESORPTIVE
CASE HL-CONTINUED
LABS SHOW VERY LOW TOTAL AND
FREE TESTOSTERONE. NO OTHER
ABNORMALITY
CASE HL
WORKUP DISCLOSED NO SECONDARY CAUSE
FOR THE HYPOGONADISM. START
TESTOSTERONE REPLACEMENT, ADD CALCIUM
1500 mg/DAY, PLUS VITAMIN D AT DOSE
SUFFICIENT TO MAINTAIN LEVEL >32 ng/ml,
ENCOURAGE EXERCISE, AND RECHECK DEXA IN
ONE YEAR. IF DEXA SHOWS NO IMPROVEMENT,
CAN CONSIDER DRUG Rx.
CASE HL TEACHING POINT 3
YOU MUST INSURE THAT THE
PATIENT’S 25-OH VITAMIN D LEVEL
IS >32 ng/ml), OR ALL THERAPIES
FOR OSTEOPOROSIS WILL FAIL.
CASE HL
TEACHING POINT SUMMARY
1. LOOK FOR UNDERLYING
CAUSES OF OP
2. DO SCREENING LABS
3. KEEP VITAMIN D >32 ng/ml
OSTEOPOROSIS IS A SYSTEMIC
SKELETAL DISEASE
CHARACTERIZED BY:
1---LOW BONE MASS
2---MICROARCHITECTURAL
DETERIORATION OF BONE
THIS RESULTS IN INCREASED BONE
FRAGILITY AND SUSCEPTIBILITY TO
FRACTURE.
BONE QUALITY, WHICH IS CLOSELY RELATED TO
BONE MICROARCHITECTURE, IS A CRUCIAL
DETERMINANT OF FRACTURE RESISTANCE
1. J Bone Miner Res . 2003;18:1932-1941.
FRACTURE RISK FACTORS
LOW T-SCORES*
H/O PREVIOUS LOW TRAUMA FRACTURE*
PROLONGED USE OF CORTICOSTEROIDS
ADVANCED AGE
POOR VISION
TENDENCY TO FALL / NEUROLOGIC DYSFUNCTION
EXCESSIVE ALCOHOL USE
HOW DO WE DETERMINE RISK
FOR FRACTURE?
(THERE IS NO PERFECT TOOL, NOT EVEN DEXA)
X-RAYS
DEXA
CLINICAL--HX/PX EXAMINATION/LABS
BONE BIOPSY/DIRECT VIS. AT SURGERY
LIMITATIONS OF DEXA
DEXA IS AN IMPERFECT TOOL FOR
ASSESSING FRACTURE RISK, BUT IT
IS THE BEST WE HAVE THUS FAR
FORTEO IS HUMAN PARATHYROID
HORMONE 1-34
H2N-
1
Ser
Val
Ser
Ile
Glu
Gln Leu
Met His
10
Asn
Teriparatide is
hPTH (1-34)
- synthetic
- recombinant
Leu
Glu
Val
20
Arg
Arg
Lys
Lys
Gly
Ser
Glu
Met
Leu
Gln Asp
30
Asn
Leu
His
Lys
Val
His
Asn Phe
Trp
Leu
40
50
60
70
INTACT PTH IS
hPTH (1-84)
80
COOH
1. Proc Natl Acad Sci USA 1974;71:384-388.
THE CHOICE OF AGENT
DEPENDS ON THE RISK
OF FUTURE FRACTURE
EQUALLY IMPORTANT IS THE MECHANISM OF
ACTION OF THE DRUG CHOSEN
SAFETY ISSUES
FORTEO® (teriparatide [rDNA origin] injection)
Important Safety Information
Warning
In male and female rats, teriparatide caused an increase in the incidence of
osteosarcoma (a malignant bone tumor), that was dependent on dose and
treatment duration. The effect was observed at systemic exposures to
teriparatide ranging from 3 to 60 times the exposure in humans given a 20-mcg
dose. Because of the uncertain relevance of the rat osteosarcoma finding to
humans, teriparatide should be prescribed only to patients for whom the
potential benefits are considered to outweigh the potential risk. Teriparatide
should not be prescribed for patients who are at increased baseline risk for
osteosarcoma (including those with Paget’s disease of bone or unexplained
elevations of alkaline phosphatase, open epiphyses, or prior external beam or
implant radiation therapy involving the skeleton) (see WARNINGS and
PRECAUTIONS, Carcinogenesis).
See Black Box Warning and Important Safety Information for FORTEO.
See full Prescribing Information for FORTEO.
FORTEO® (teriparatide [rDNA origin] injection)
Indications for FORTEO
 FORTEO is indicated for the treatment of postmenopausal
women with osteoporosis who are at high risk for fracture
 FORTEO is indicated to increase bone mass in men with
primary osteoporosis or osteoporosis associated with
hypogonadism, who are at high risk for fracture
 Individuals at high risk for fracture include those who
(based on physician assessment):




Have a history of osteoporotic fracture, or
Have multiple risk factors for fracture, or
Failed previous osteoporosis therapy, or
Are intolerant to previous osteoporosis therapy
See Black Box Warning and Important Safety Information for FORTEO.
See full Prescribing Information for FORTEO.
FORTEO® (teriparatide [rDNA origin] injection)
Important Safety Information
Adverse Events
Warnings
The following categories of patients have
increased baseline risk of
osteosarcoma and therefore should
not be treated with FORTEO:
Paget’s disease of bone
Pediatric populations and young adults with
open epiphyses
Prior external beam or implant radiation therapy
involving the skeleton
Patients with any of the following
conditions also should not receive
FORTEO:
Bone metastases or a history of skeletal
malignancies
Metabolic bone diseases other than
osteoporosis
Pre-existing hypercalcemia
Pregnancy and lactation
 Adverse events usually were mild
and generally did not require
discontinuation of therapy
 Early discontinuation due to adverse
events occurred in 5.6% of patients
assigned to placebo and 7.1% of
patients assigned to FORTEO
 Reported adverse events that
appeared to be increased by
FORTEO treatment were dizziness
and leg cramps
See Black Box Warning and Important Safety Information for FORTEO.
See full Prescribing Information for FORTEO.
FORTEO® (teriparatide [rDNA origin] injection)
Important Safety Information
Contraindication:
 FORTEO should not be given to patients with hypersensitivity to teriparatide or to any of its excipients.
Precautions: General
 The safety and efficacy of FORTEO have not been evaluated beyond 2 years of treatment.
Consequently, use of the drug for more than 2 years is not recommended.
 FORTEO should be used with caution in patients with active or recent urolithiasis or taking digitalis.
 Transient episodes of symptomatic orthostatic hypotension were observed infrequently in short-term
pharmacology studies.
 Limited information is available to evaluate safety in patients with hepatic, renal, and cardiac disease.
 In laboratory tests, FORTEO transiently increases serum calcium, with the maximal effect observed at
approximately 4 to 6 hours post-dose. By 16 hours post-dose, serum calcium generally has returned
to, or near, baseline.
Additional Safety Information
 Persistent hypercalcemia was not observed in clinical trials with FORTEO.
 No clinical adverse events associated with increases in serum or urine calcium and serum uric acid
were observed.
 No clinically important adverse renal effects were observed in clinical studies.
See Black Box Warning and Important Safety Information for FORTEO.
See full Prescribing Information for FORTEO.
FORTEO® (teriparatide [rDNA origin] injection)
Dosage and Administration
 The FORTEO Pen is a multidose, prefilled delivery device that can
be used up to 4 weeks (28 daily doses), including the first injection
from the pen
 Dose: 20 mcg once a day
 Do not transfer the contents of the pen into a syringe
 Needle (29- to 31-gauge) must be changed after each use
 Administered as a subcutaneous injection into the thigh or
abdominal wall
 Duration of therapy: 18-24 months
See Black Box Warning and Important Safety Information for FORTEO.
See full Prescribing Information for FORTEO.
WARNING
IN MALE AND FEMALE RATS, TERIPARATIDE CAUSED AN INCREASE IN
THE INCIDENCE OF OSTEOSARCOMA (A MALIGNANT BONE TUMOR),
THAT WAS DEPENDENT ON DOSE AND TREATMENT DURATION. THE
EFFECT WAS OBSERVED AT SYSTEMIC EXPOSURES TO TERIPARATIDE
RANGING FROM 3 TO 60 TIMES THE EXPOSURE IN HUMANS GIVEN A
20-MCG DOSE. BECAUSE OF THE UNCERTAIN RELEVANCE OF THE RAT
OSTEOSARCOMA FINDING TO HUMANS, TERIPARATIDE SHOULD BE
PRESCRIBED ONLY TO PATIENTS FOR WHOM THE POTENTIAL
BENEFITS ARE CONSIDERED TO OUTWEIGH THE POTENTIAL RISK.
TERIPARATIDE SHOULD NOT BE PRESCRIBED FOR PATIENTS WHO ARE
AT INCREASED BASELINE RISK FOR OSTEOSARCOMA (INCLUDING
THOSE WITH PAGET’S DISEASE OF BONE OR UNEXPLAINED
ELEVATIONS OF ALKALINE PHOSPHATASE, OPEN EPIPHYSES, OR
PRIOR RADIATION THERAPY INVOLVING THE SKELETON) (SEE
WARNINGS AND PRECAUTIONS, CARCINOGENESIS).
FORTEO®
WARNINGS
•
•
THE FOLLOWING CATEGORIES OF PATIENTS HAVE INCREASED
BASELINE RISK OF OSTEOSARCOMA AND THEREFORE SHOULD
NOT BE TREATED WITH FORTEO:
– PAGET’S DISEASE OF BONE
– PEDIATRIC POPULATIONS
– PRIOR RADIATION RX INVOLVING THE SKELETON
PATIENTS WHO HAVE ANY OF THE FOLLOWING CONDITIONS
ALSO SHOULD NOT RECEIVE FORTEO:
– BONE METASTASES OR A HISTORY OF SKELETAL
MALIGNANCIES
– METABOLIC BONE DISEASES OTHER THAN
OSTEOPOROSIS
– PRE-EXISTING HYPERCALCEMIA
– PREGNANCY AND LACTATION
(FORTEO®) TERIPARATIDE (rDNA ORIGIN)
INJECTION
PRECAUTIONS: GENERAL
• THE SAFETY AND EFFICACY OF FORTEO HAVE NOT
BEEN EVALUATED BEYOND 2 YEARS OF TREATMENT.
CONSEQUENTLY, USE OF THE DRUG FOR MORE THAN
2 YEARS IS NOT RECOMMENDED.
• FORTEO SHOULD BE USED WITH CAUTION IN
PATIENTS
– WITH ACTIVE OR RECENT UROLITHIASIS
– TAKING DIGITALIS
• LIMITED INFORMATION IS AVAILABLE TO EVALUATE
SAFETY IN PATIENTS WITH HEPATIC, RENAL, AND
CARDIAC DISEASE.
TERIPARATIDE SUMMARY OF SIDE EFFECTS-LAB
• SAFETY EVALUATION: 24 CLINICAL TRIALS-OVER 2800 WOMEN AND
MEN
• HYPERCALCEMIA WAS ABSENT OR MILD AND TRANSIENT (MAX 4 TO
6 HOURS POST-DOSE NORMAL AT 24 HOURS)-NO PERSISTENT
HYPERCALCEMIA
• MEAN 24-HR Ur CA INCREASED 30 MG/DAY
• MEAN SERUM URIC ACID INCREASED 13-20% (NO SEQUELAE SUCH
AS ACUTE GOUT)
• CHANGES REVERSED AFTER FORTEO WITHDRAWAL
• NO CLINICAL ADVERSE EVENTS WERE ASSOCIATED WITH
INCREASES IN SERUM OR URINE CALCIUM
TERIPARATIDE SUMMARY OF SIDE
EFFECTS-CLINICAL
•ADVERSE EVENTS USUALLY WERE MILD AND GENERALLY
DID NOT REQUIRE DISCONTINUATION OF THERAPY.
•EARLY DISCONTINUATION DUE TO ADVERSE EVENTS
OCCURRED IN 5.6% OF PLACEBO PATIENTS AND 7.1% OF
FORTEO PATIENTS.
•REPORTED ADVERSE EVENTS THAT APPEARED TO BE
INCREASED BY FORTEO TREATMENT WERE DIZZINESS
AND LEG CRAMPS.
•TRANSIENT EPISODES OF SYMPTOMATIC ORTHOSTATIC
HYPOTENSION WERE OBSERVED INFREQUENTLY.
TERIPARATIDE INDICATION IN
POSTMENOPAUSAL WOMEN
FORTEO IS INDICATED FOR THE TREATMENT OF
POSTMENOPAUSAL WOMEN WITH OSTEOPOROSIS
WHO ARE AT HIGH RISK FOR FRACTURE.
THESE INCLUDE THOSE WHO (BASED ON PHYSICIAN
ASSESSMENT) …
• HAVE A HISTORY OF OSTEOPOROTIC FRACTURE
• HAVE MULTIPLE RISK FACTORS FOR FRACTURE
• FAILED PREVIOUS OSTEOPOROSIS THERAPY
• ARE INTOLERANT TO PREVIOUS OSTEOPOROSIS
THERAPY
TERIPARATIDE INDICATION IN
MEN
FORTEO IS INDICATED TO INCREASE BONE MASS IN
MEN WITH PRIMARY OSTEOPOROSIS OR
OSTEOPOROSIS ASSOCIATED WITH HYPOGONADISM,
WHO ARE AT HIGH RISK FOR FRACTURE.
THESE INCLUDE THOSE WHO (BASED ON PHYSICIAN
ASSESSMENT) …
• HAVE A HISTORY OF OSTEOPOROTIC FRACTURE
• HAVE MULTIPLE RISK FACTORS FOR FRACTURE
• FAILED PREVIOUS OSTEOPOROSIS THERAPY
• ARE INTOLERANT TO PREVIOUS OSTEOPOROSIS
THERAPY
PERCENTAGE CHANGE (MEAN {+/-} SE) FROM BASELINE
IN LUMBAR SPINE BONE MINERAL DENSITY
McClung, M. R. et al. Arch Intern Med 2005;165:1762-1768.
Copyright restrictions may apply.
MO
PERCENTAGE CHANGE (MEAN {+/-} SE) FROM BASELINE TO
MONTH 18 IN FEMORAL NECK BONE MINERAL DENSITY
McClung, M. R. et al. Arch Intern Med 2005;165:1762-1768.
Copyright restrictions may apply.
RAT CARCINOGENICITY STUDY
• 2-YEAR RAT STUDY REQUIRED BY FDA RULES
– EXAGGERATED SKELETAL RESPONSE TO TPTD
– DOSE-RELATED BONE PROLIFERATIVE LESIONS
INCLUDING OSTEOSARCOMA
– NO INCREASE IN SOFT-TISSUE NEOPLASMS
• FOLLOW-UP RAT STUDY
– DOSE AND DURATION OF TREATMENT ARE PRIMARY
FACTORS IN DEVELOPMENT OF RAT BONE TUMORS
– ROLE OF AGE AT INITIATION OF TREATMENT IS NOT
CONCLUSIVE
Vahle JL, et al. Toxicologic Pathology 2002;30:312-321
Vahle JL, et al. J Bone Miner Res 2002;17:Suppl 1
IS THIS A WORRY?
THIS RAT STRAIN HAS ABOUT A 5% SPONTANEOUS
INCIDENCE OF OS IN THEIR NATURAL STATE.
BONE STRUCTURE, GROWTH AND REMODELING IN RATS
DIFFERS IN MANY IMPORTANT WAYS FROM HUMANS.
RAT BONES RESPOND TO RAT PTH VERY DIFFERENTLY
THAN HUMAN BONES RESPOND TO HUMAN PTH. SO
THE SIGNIFICANCE OF RESULTS USING HUMAN PTH IN
RATS IS NOT CLEAR.
RATS GOT VERY HIGH DOSES OF PTH FOR MOST OF
THEIR LIVES. THIS WILL NEVER OCCUR IN HUMANS
TREATED WITH PTH.
IS THIS A WORRY?
EVEN IN CASES OF HUMAN HYPERPARATHYROIDISM, IN
WHICH PTH LEVELS MAY BE CONTINUALLY HIGH FOR
YEARS, THERE HAVE BEEN NO INCREASE IN EXPECTED
CASE RATES OF OSTEOGENIC SARCOMA IDENTIFIED.
HOWEVER, OSTEOGENIC SARCOMA IS A VERY RARE
TUMOR: 4 CASES PER MILLION, AND OF THOSE, 2 ARE
ASSOCIATED WITH PAGET’S DISEASE.
THERE IS NO EVIDENCE THAT HUMAN PTH CAUSES
OSTEOGENIC SARCOMA IN HUMANS.
TERIPARATIDE (FORTEO) REDUCES THE RISK
OF NEW VERTEBRAL FRACTURES
Relative Risk 0.35
95% CI, 0.22 to 0.551
16
14
% WITH
12
NEW
VERTEBRAL 10
FRACTURE(S) 8
N=64
Risk Reduction
Relative: 65%*
Absolute: 9.3%*
6
4
N=22
2
0
1. N Engl J Med. 2001;344:1434-1441.
Placebo
FORTEO
(n=448)
(n=444)
*p <.001
FORTEO REDUCES THE RISK OF
MULTIPLE NEW VERTEBRAL
FRACTURES
Relative Risk 0.23,
95% CI, 0.09 to 0.601
6
5
% WITH 2 OR
MORE
NEW
VERTEBRAL
FRACTURES
N=22
4
3
Risk Reduction
2
Relative: 77%†
Absolute: 3.8%†
1
N=5
0
Placebo
FORTEO
(n=448)
(n=444)
1. N Engl J Med. 2001;344:1434-1441.
*p <.001
FORTEO REDUCES THE RISK OF
NONVERTEBRAL FRAGILITY FRACTURES1
6% WITH
NONVERTEBRAL
FRAGILITY
FRACTURES
5-
N=30
453%
32-
N=14
10
1
Placebo
FORTEO
(n-544)
(n=541)
defined as occurring with minimal trauma
Neer RM, et al. N Engl J Med. 2001;344:1434-1441
Risk Reduction
Relative: 53%†
Absolute: 3.0%†
STRONTIUM
RANELATE
BUILDING
INCREASES
RESORPTION
DECREASES
UNCOUPLES BUILDING AND
RESPORPTION, IN FAVOR OF BUILDING,
SO NET EFFECT IS THAT BONE MASS
AND STRENGTH INCREASE
0
0
AMG 162
AMG 162
BLOCKS RANKL
IBANDRONATE (BONIVA) PO, IV
ZOLEDRONATE (ZOMETA) IV
STRONTIUM RANELATE
TERIPARATIDE (FORTEO) SQ
AMG 162 (RANKL INHIBITOR)
MODE OF DELIVERY DETERMINES
SKELETAL RESPONSE TO PTH
PTH
once-daily
 osteoblast
apoptosis
bone
lining
cells
 cbfa1
(pre-OB)
 osteoblast number/function
 bone formation
 bone mass/strength
continuous
 RANKL
 OPG
 osteoclast
 bone resorption
 serum Ca++
Incidence of Osteoporotic Fractures in Women
After Age 501
Annual Incidence per
1000 Women
40
Vertebrae
30
20
Hip
10
Wrist
0
50
60
70
Age (Years)
1. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 4th ed. Philadelphia, PA: Lippincott Williams &
Wilkins;1999:257-259.
80
FORTEO® (teriparatide [rDNA origin] injection)
Time Effect to New Nonvertebral Fragility Fracture1
7
Placebo (n=544)
% of Women*
6
5
4
3
2
FORTEO (n=541)
1
0
0
2
4
6
8
10
12
14
16
18
Months Since Randomization
*Percent of women who had one or more nonvertebral fragility fractures during the study.
1. N Engl J Med. 2001;344:1434-1441.
See Black Box Warning and Important Safety Information for FORTEO.
See full Prescribing Information for FORTEO.
20
BMD (Mean % Change ± SE)
FORTEO® (teriparatide [rDNA origin] injection)
Increased Lumbar Spine BMD in Postmenopausal Women
With Osteoporosis*,1
*266
14
11.8%†
12
9.4%†
10
6.9%†
8
6
FORTEO (n=129)
3.9%†
4
2
0
Placebo (n=137)
0
3
6
9
12
Months since randomization
15
18
subjects treated for 18 months and with data available at all time points. †p<0.001 for FORTEO vs. placebo at each post-baseline time point.
1. FORTEO [Package insert]. Indianapolis, IN:
Eli Lilly and Company; 2004.
See Black Box Warning and Important Safety Information for FORTEO.
See full Prescribing Information for FORTEO.
FORTEO REDUCES THE RISK OF
NEW NONVERTEBRAL FRAGILITY FRACTURES
6
RR 0.47 (0.25, 0.88), p<0.05
5
% W/ NEW
FRAGILITY
FRACTURES
4
3
2
1
0
All
Radius/
Wrist
Ribs
Foot/
Ankle
Neer RM, et al. N Engl J Med. 2001;344:1434-1441
Hip Humerus Pelvis Other
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