2. LEARNING OBJECTIVES
1. DISCUSS DIAGNOSIS OF OSTEOPOROSIS.
2. REVIEW MANAGEMENT OF OSTEOPOROSIS.
3. IDENTIFY KEY ISSUES IN OSTEOPOROSIS PREVENTION.
3. WHY CARE ABOUT OSTEOPOROSIS?
• IN THE US, THE MAJORITY OF PATIENTS WITH FRAGILITY FRACTURES DO NOT RECEIVE
OSTEOPOROSIS THERAPY.
• IN ONE STUDY OF WOMEN > 65 YO WITH RECENT HIP FRACTURE, 13% WERE RECEIVING
ADEQUATE TREATMENT FOR OSTEOPOROSIS.
5. RESULTS
• 61.5% HAD MODERATE TO SEVERE VITAMIN D DEFICIENCY WITH LEVELS LESS THAN 50
NMOL/L.
• 9.1% OF THE POPULATION HAD OSTEOPOROSIS, AND 38.6% HAD OSTEOPENIA.
• THERE WAS NO SIGNIFICANT CORRELATION BETWEEN SPINE OR TOTAL FEMORAL BMD
AND SERUM 25(OH) D.
Alkhenizan A, Mahmoud A, Hussain A,Gabr A, Alsoghayer S, Eldali A (2017)
The Relationship between 25 (OH) D Levels (Vitamin D) and Bone Mineral
Density (BMD) in a Saudi Population in a Community-Based Setting.
PLoS ONE 12(1): e0169122. doi:10.1371/journal. pone.0169122
Published: January 3, 2017
6.
7.
8. BONE MINERAL DENSITY TEST
DXA (DUAL ENERGY X-RAY
ABSORPTIOMETRY)
• THE WHO CRITERIA FOR OSTEOPOROSIS ARE BASED ON DXA.
• HIP DXA IS THE BEST PREDICTOR OF HIP FRACTURE, WHICH IS THE MOST CLINICALLY
RELEVANT SITE OF FRACTURE.
15. VITAMIN D METABOLISM
• D3 (CHOLECALCIFEROL) AND D2 (ERGOCALCIFEROL) ARE BOTH BIOLOGICALLY ACTIVE.
• D2 OR D3 CONVERTED IN LIVER BY HYDROXYLATION INTO 25 OH VIT D AND THEN
CONVERTED IN KIDNEY TO 1,25 DI-OH VIT D.
• 25 OH VIT D HAS LOW BIOLOGICAL ACTIVITY BUT IS THE MAJOR FORM IN
CIRCULATION: BEST MARKER FOR NUTRITIONAL STATUS OF: VIT D.
16. 1. A 72 YO OBESE AFRICAN AMERICAN WOMAN COMPLAINS OF
SUDDEN ONSET OF MID-BACK PAIN. X-RAY CONFIRMS T4
VERTEBRAL COMPRESSION FRACTURE AND DIFFUSE OSTEOPENIA.
YOUR NEXT STEP:
A. RECOMMEND WEIGHT REDUCTION AND EXERCISE, START VITAMIN D3 AND
CALCIUM
B. CHECK VITAMIN D LEVEL AND BEGIN ALENDRONATE 70 MG WEEKLY
C. ORDER DEXA SCAN
D. WORK UP FOR SECONDARY CAUSES OF OSTEOPOROSIS
17. PRIMARY (IDIOPATHIC) OSTEOPOROSIS
• SHORT STATURE, SLENDER, CAUCASIAN WOMEN ARE AT GREATER RISK FOR
OSTEOPOROSIS.
• RISK OF OSTEOPOROSIS IN MEN BECOMES SIMILAR TO WOMEN IN ADVANCED AGE
(>80).
• ALCOHOL AND CIGARETTE SMOKING ACCELERATE THIS RISK.
• OSTEOPOROTIC FRACTURES USUALLY BEGIN IN VERTEBRAE UNDER GREATEST
ANATOMICAL LOAD (T10-T12) AND SPREAD CAUDAL AND CEPHALAD.
20. • POSTMENOPAUSAL WOMEN AND MEN > 50 YO
– HIP OR VERTEBRAL FRACTURE
– PRIOR FRACTURES AND LOW BONE MASS
– T SCORE ≤ -2.5 AFTER APPROPRIATE EVALUATION FOR OTHER CAUSES
– LOW BONE MASS (T SCORE -1 TO -2.5) IF HIGH RISK (EG,GLUCOCORTICOID USE)
24. 2. WHICH OF THE FOLLOWING IS THE USPSTF’S RECOMMENDATION REGARDING DAILY
SUPPLEMENTATION OF VITAMIN D AND CALCIUM FOR NON-INSTITUTIONALIZED
POSTMENOPAUSAL WOMEN TO PREVENT FRACTURE?
A. SUPPLEMENTAL VITAMIN D3 AND CALCIUM IS NOT RECOMMENDED
B. 20 MCG 25-HYDROXYVITAMIN D + 800 MG CALCIUM
C. 400 IU/DAY OF VITAMIN D3 + 1000 MG CALCIUM
D. 800 IU/DAY OF VITAMIN D3 + 1200 MG CALCIUM
25. VITAMIN D AND CALCIUM: USPSTF
• RECOMMENDS AGAINST DAILY SUPPLEMENTATION WITH D3 400 IU OR LESS AND
CALCIUM 1000 MG OR LESS.
• CONCLUDES THAT EVIDENCE IS INSUFFICIENT TO ASSESS BENEFITS/HARMS OF HIGHER
DOSES.
• GUIDELINE DOES NOT ADDRESS VIT D AND CALCIUM SUPPLEMENTS FOR WOMEN OR
MEN WITH ESTABLISHED OSTEOPOROSIS.
26. VITAMIN D AND CALCIUM
• NATIONAL OSTEOPOROSIS FOUNDATION STILL RECOMMENDS CALCIUM AND VITAMIN D
SUPPLEMENTATION (1200 MG CALCIUM,800-1000 IU VITAMIN D3) FOR ALL
POSTMENOPAUSAL WOMEN.
27. VITAMIN D AND CALCIUM: USPSTF
• VIT D SUPPLEMENTATION CAN REDUCE RISK OF FRACTURE (INSTITUTIONALIZED
ELDERLY > COMMUNITY DWELLING); DOSE > 800 IU D3 IN FREQUENT FALLERS (BUT
RECENT RANDOMIZED TRIAL FAILED TO CONFIRM THIS).
• NO CLEAR BENEFIT (OR HARM) IN CANCER OR CARDIAC RISK.
• NEARLY ALL STUDIES OF OSTEOPOROSIS RX (E.G.,BISPHOSPHONATES) INCLUDE VITAMIN
D/CA SUPPLEMENTATION.
28. TREATMENT OF OSTEOPOROSIS
• PREVENT HIP FRACTURES AND VERTEBRAL FRACTURES: ALENDRONATE (FOSAMAX),
RISEDRONATE (ACTONEL), TERIPARATIDE (FORTEO), DENOSUMAB
• PREVENT VERTEBRAL FRACTURES (I.E., STUDIES HAVE NOT CONFIRMED PREVENTION OF
HIP FRACTURE): IBANDRONATE (BONIVA), RALOXIFENE (EVISTA)
29. BISPHOSPHONATES
• GIVEN ON AN EMPTY STOMACH WITH FULL GLASS OF WATER
• CONTRAINDICATIONS:
– ESOPHAGEAL STRICTURE
– ACHALASIA
– PATIENT UNABLE TO STAND OR SIT UPRIGHT
– RENAL FAILURE WITH CREATININE CLEARANCE OF < 35 ML/MINUTE
– HYPOCALCEMIA
• WHAT TO DO ?!
30. BISPHOSPHONATES:
OSTEONECROSIS OF JAW
• LOW INCIDENCE.
• MOST OFTEN WITH IV BISPHOSPHONATES.
• MOSTLY IN CANCER PATIENTS.
• MAINTAIN ORAL HYGIENE & REGULAR DENTAL CARE.
31. BISPHOSPHONATE RX: HOW LONG?
• FLEX TRIAL: 1100 WOMEN, ALENDRONATE THERAPY AVERAGED 5 YEARS; RANDOMIZED
TO CONTINUE 5 MORE YEARS OR STOP
• CLINICAL VERTEBRAL FRACTURE RISK LOWER FOR CONTINUED TREATMENT, ESPECIALLY
IN TWO GROUPS: THOSE WITHOUT PRE-EXISTING FRACTURE & T SCORE < -2.5 OR
PREEXISTING FRACTURE & T SCORE < -2.0 (NNT 21 & 17 RESPECTIVELY)
• NO DATA FOR NON-VERTEBRAL FRACTURE
32. CALCITONIN
• CALCITONIN: POLYPEPTIDE HORMONE
• INTRANASAL FORMULATION FOR VERTEBRAL FRACTURE COMPLICATED BY PAIN FOR
ANALGESIC BENEFIT.
• WEAK ANTI-FRACTURE EFFICACY.
• REMEMBER TO PRESCRIBE CALCIUM AND VITAMIN D!
• INCREASED RISK OF CANCER WITH LONG-TERM USE?
LIMIT TO SIX MONTHS’ DURATION.
33. RALOXIFENE
• SELECTIVE ESTROGEN RECEPTOR MODULATOR (SERM)
• ESTROGEN AGONIST/ANTAGONIST
• REDUCES RISK OF BREAST CANCER
• DOES NOT STIMULATE ENDOMETRIUM
• HOT FLASHES
• HAS NOT BEEN SHOWN TO REDUCE HIP FRACTURE RISK; LESS POTENT THAN
BISPHOSPHONATES
34. TERIPARATIDE (PTH)
PARATHYROID HORMONE (1-34)
• DAILY SQ INJECTIONS.
• RESERVED FOR PTS WITH HIGH RISK FOR FRACTURES:
‒ MULTIPLE FRACTURES
‒ EXTREMELY LOW BMD EG, < -3
‒ INTOLERANT/UNRESPONSIVE TO OTHER RX
• FDA BLACK BOX WARNING: OSTEOSARCOMA (ANIMALS); THUS, SAFETY AND EFFICACY ? > 2
YRS.
• CONSIDER SUBSTITUTING DENOSUMAB OR BISPHOSPHATE > 2 YRS.
• SEVERE OSTEOPOROSIS (T-SCORE OF -3.5 OR BELOW EVEN IN THE ABSENCE OF FRACTURES,
OR T-SCORE OF -2.5 OR BELOW PLUS A FRAGILITY FRACTURE)
35. DENOSUMAB
• MONOCLONAL ANTIBODY AGAINST RANKL (RECEPTOR THAT STIMULATES
OSTEOCLASTIC ACTIVITY).
• REDUCES VERTEBRAL, HIP, AND NON-VERTEBRAL FRACTURES.
• NO LONG-TERM SAFETY DATA; 1%-2% SEVERE HYPOCALCEMIA.
• Q 6 MONTH INJECTION (EXPENSIVE).
• FOR PT WITH IMPAIRED RENAL FUNCTION.
• DO NOT MEET CRITERIA FOR SEVERE OSTEOPOROSIS BUT HAVE HAD FRAGILITY
FRACTURES.
