Update: Osteoporosis
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  • Country specific
  • NOF clinicians guide : Endorsed by: AA clinical endocrinologists ACOG AC radiology AC rheumatology American Geriatric Society American orthopedic assn
  • .
  • RISK Factors : weighted.
  •  
  • Medicare coverage : Including but not limited to. ≥ 5mg daily for 3 months.

Update: Osteoporosis Presentation Transcript

  • 1. Update in Osteoporosis Teresa Bryan, M.D. General Medicine Noon Conference February 24, 2009
  • 2. Objectives
    • WHO Task Force Fracture Risk Assessment Tool (FRAX)
    • NOF Guidelines for pharmacologic intervention in postmenopausal women and men ≥ age 50
    • ACP Practice Guidelines for Screening in Men
    • ACP Practice Guidelines for Pharmacologic Therapy
    • Association of Atrial fibrillation with bisphosphonates
    • Bisphosphonate associated osteonecrosis of the jaw
  • 3. Background
    • Estimated 44 million Americans
    • 55% people 50 years of age or older
    • 1 out of every 2 Caucasian women will experience osteoporotic fracture and 1 out of every 5 men.
    • Hip fractures result in 10-20% excess mortality in 1 year.
    • 20% hip fracture patients require long-term nursing home care.
  • 4. US Preventive Services Task Force Recommendations Ann Int Med. 2002;137:526-528
    • Routinely screen women 65 years of age and older.
    • Screen women at increased risk beginning at 60 years of age.
    • No recommendation for or against routine screening in women younger than 60 years of age.
  • 5. Definitions
    • Osteoporosis : a skeletal disorder characterized by compromised bone strength predisposing to an increased risk for fracture. Diagnosed by:
      • Occurrence of fragility fracture
      • Osteoporosis by DXA criteria
    • Osteoporotic fracture : (fragility fracture) those occurring from a fall from a standing height or less without major trauma such as a MVA.
  • 6. Dexa Interpretation
    • T score : Difference in SDs compared to value of young adults same sex.
    • Z score : Difference in SDs compared to value of individuals same age and sex.
    • Osteoporosis : T score ≤-2.5
    • Osteopenia : T score between -1 and -2.5
        • SD=Standard Deviation
  • 7. Osteoporotic Risk Assessment
    • Majority of fracture occur in those with low bone mass rather than osteoporosis
    • WHO Fracture Risk Assessment Tool (FRAX)
    • Considers 9 clinical risk factors for osteoporosis
  • 8. FRAX Risk Factors
    • Age
    • Previous Fracture
    • Parent with h/o hip fracture
    • Current smoking
    • Glucocorticoids > 3 months
    • Rheumatoid arthritis
    • Secondary osteoporosis
    • Alcohol 3 or more units daily
    • Bone Mineral Density
  • 9. WHO Fracture Risk Assessment Tool (FRAX) http://www.shef.ac.uk/FRAX/
  • 10. WHO Fracture Assessment Tool http://www.shef.ac.uk/FRAX/
  • 11. Applications of FRAX in US
    • Not intended for young adults or children
    • Only applies to previously untreated patients
    • Total hip density may be substituted for femoral neck BMD
    • Convert T score based on reference standard used in FRAX
  • 12. Cost-effectiveness
    • Intervention threshold: 10 year fracture probability 2.5 to 4.9%
    • Assumes annual treatment cost of $600
    • “Willingness to pay” threshold of $60,000 per QALY gained
    Osteoporosis International Dec 2007 http://www.nof.org/professionals/Cost-effective_osteoporosis_%20treatment_US.pdf
  • 13. http://www.nof.org/professionals/NOF_Clinicians_Guide.pdf
  • 14. National Osteoporosis Foundation Screening Recommendations
    • Women 65 and older
    • Men 70 and older
    • Postmenopausal and perimenopausal women with increased risk factor profile (low body wt, prior fx, meds)
    • Men 50-70 with increased risk factor profile
    • Fracture after age 50
    • Consider in postmenopausal women discontinuing estrogen.
  • 15. Risk Factors NEJM 2008;358:1474-82.
  • 16. Secondary Osteoporosis
    • Type 1 DM
    • Osteogenesis imperfecta
    • Untreated, longstanding hyperthyroidism
    • Hypogonadism
    • Premature menopause <45 year.
    • Chronic malnutrition
    • Malabsorption
    • Chronic liver disease
    • Meds: anticonvulsants, heparin, glucocorticoids
  • 17. Clinical Assessment of Osteoporosis in Postmenopausal Women and Men >50
    • History and physical exam
    • Consider laboratory tests: (esp if Z<2.0)
      • Ca, phos, Cr, LFTs, TSH, CBC, VIt D level
      • Testosterone level in men
    • If clinically indicated:
      • SPEP, Urine cortisol, Urine calcium, anti-tissue transglutaminase antibodies (Celiac sprue)
  • 18. Pharmacologic Therapy (NOF Recommendations for Postmenopausal Women and Men >50)
    • Hip or vertebral fracture
    • T score ≤ -2.5 femoral neck, total hip or spine
    • T score -1 to -2.5 hip or spine:
      • 10 year hip fx probability ≥ 3%*
      • 10 year all major osteoporosis related fx probability ≥ 20% *
    *WHO absolute fracture risk model
  • 19. Case
    • 57 year old woman. Healthy.
    • FH: 80 year old mother with mult vertebral fx and “hump” in her back
    • Prior fx: cervical spine when fell off bed playing with grandson
    • No smoking, no ETOH, no prior prednisone, no RA or secondary causes
    • Weight: 155 lb Height 5ft 6 in
  • 20. Case (cont)
    • T score -2.4
    • Frax assessment tool : 10 year probability of fx
      • Major osteoporotic : 21%
      • Hip : 4.9
  • 21. Universal Recommendations
    • Adequate intake of calcium and vitamin D:
      • Adults > 50: 1200 mg elemental calcium /day
      • All adults > 50: 800-1000 IU/day
    • Regular Weight Bearing Exercise:
      • At least 30 min 3x weekly
    • Fall prevention strategies:
      • Correct vision and hearing problems
      • Evaluate neuro problems
      • Review meds for Side effects
    • Avoid tobacco and alcohol
  • 22. Treatment Options FDA Approved
    • Bisphosphonates
    • Estrogen
    • SERMS (Selective Estrogen Receptor Modulators)
    • Calcitonin
    • Forteo (parathyroid hormone)
  • 23. Bisphosphonates
    • Alendronate (fosamax): 10 mg qd or 70 q week
    • Risedronate (actonel): 5 mg qd or 35mg q week
    • Ibandronate (Boniva): 2.5mg qd, 150 mg q month, 3mg IV q3 months
    • Zolendronic acid (Reclast): 5mg IV yearly
    • Treatment efficacy:
        • Bisphosphonates decrease risk vertebral fracture by approx 50%
        • Risk of hip fracture decreased by 37%
  • 24. Estrogen Agonists/Antagonists (Formerly SERMS)
    • Raloxifene (Evista)
    • Decreased vertebral fx 30%-55%
    • 60 mg qd
    • Increase risk DVT
    • No effect on endometrium
    • Decreases risk of breast cancer
    • Causes hot flashes (6%)
  • 25. Calcitonin
    • Miacalcin: nasal, SQ or IM
    • 200 IU intranasally qd
    • 25-39% reduction vertebral
    • Possible analgesic action for acute osteoporotic fracture
  • 26. PTH (Teriparatide)
    • Forteo 20 ug SQ daily
    • Previous failed therapy
    • Decrease vertebral fx 65%
    • Osteosarcoma in rats
    • Expensive
  • 27. Estrogen
    • FDA approved
      • Osteoporosis prevention
      • Vasomotor symptoms
      • Vulvovaginal atrophy
    • Progesterone combination if no hysterectomy
    • Risk MI/Stroke/Breast CA
    • Consider non-estrogen treatment first
  • 28. Monitoring Effectiveness
    • Monitor and encourage compliance
    • Review risk factor modification
    • Calcium and vitamin D intake
    • Repeat BMD q 2 years (medicare guidelines)
  • 29. Osteoporosis in Men
    • 1.5 million men over age 65 in US have osteoporosis
    • Mortality with hip fractures higher in men up to 37.5%
    • Absolute BMD in men who fracture hip is higher than in women.
    • Prevalence:
      • 7% white men
      • 5% black men
      • 3% Hispanic men
  • 30. Case
    • 68 year old WM
    • COPD
    • Stopped smoking 9 years ago
    • 2 prior pred tapers x 2 weeks
    • Wt 180 lb, Ht 5 ft 8in
    • No alcohol, RA
    • FH negative
    • Frequent yard work
  • 31. ACP Guidelines for Screening in Men Risk Factors
    • Age >70 years
    • Low body weight (BMI<20-25 kg/m 2)
    • Weight loss > 10%
    • Physical inactivity
    • Use of oral corticosteroids
    • Previous fragility fracture
    Ann Intern Med 2008;148:680-684.
  • 32. Common Secondary Causes in Men
    • Cushing’s or steroid therapy
    • Excessive alcohol use
    • Hypogonadism
    • Low calcium intake of Vit D insufficiency
    • Smoking
    • Family history of minimal trauma fracture
    Ann Intern Med 2008;148:680-684
  • 33. ACP Guidelines in Men Recommendations
    • 1- Perform individualized assessment of risk factors for osteoporosis in older men (Strong recommendation; high-quality evidence)
    • 2- Obtain DXA for men who are at increased risk for osteoporosis and are candidates for drug therapy (Strong recommendation; moderate-quality evidence)
    • 3- Further research to evaluate osteoporosis screening tests in men
    Ann Intern Med 2008;148:680-684
  • 34. Treatment in Men
    • Treat secondary causes
    • Bisphosphonates reasonable first line
    • Teriparatide
    • Calcitonin
    • Raloxifene not well studied in men
  • 35. Pharmacologic Treatment of Low Bone Density or Osteoporosis to Prevent Fractures: A Clinical Practice Guideline from the ACP (Ann Intern Med 2008;149:404-415.)
    • What are the comparative benefits in fracture reduction among treatments for low bone density?
    • How does fracture reduction resulting from treatments vary among individuals with different fracture risks?
    • What are the short and long-term adverse effects and do these vary by specific subpopulations?
  • 36. Effect of Bisphosphonates on Fracture Risk Reduction Annals 2008;149:404-415 ↓ ↓ ↓ Risedronate ↓ ↓ ↓ Zoledronic acid Not studied ↔ ↓ Ibandronate ↓ ↓ ↓ Alendronate Hip Nonvertebral Vertebral
  • 37. Copyright restrictions may apply. Black, D. M. et al. JAMA 2006;296:2927-2938. BMD Change in FLEX Participants
  • 38. Copyright restrictions may apply. Black, D. M. et al. JAMA 2006;296:2927-2938. Incidence of Fracture by Treatment Group
  • 39. Effect on Fracture Risk Reduction Annals 2008;149:404-415 ↔ Not studied ↔ Tamoxifene ↔ ↔ ↓ Raloxifene modest ↓ modest ↓ modest ↓ Calcium +Vit D Not studied ↓ ↓ Teriparatide ↓ ↓ ↓ Estrogen Not studied ↔ ↓ Calcitonin Hip Nonvertebral Vertebral
  • 40. MacLean, C. et. al. Ann Intern Med 2008;148:197-213 Risk for hip fractures relative to placebo for participants who are at high risk for fracture, by agent
  • 41. MacLean, C. et. al. Ann Intern Med 2008;148:197-213 Risk for hip fracture relative to placebo for participants who are not at high risk for fracture, by agent
  • 42. ACP Recommendations
    • 1- Offer pharmacologic treatment to men and women who have known osteoporosis and to those with h/o fragility fractures. (Strong recommendation; high-quality evidence)
    • 2- Consider treatment for men and women at risk for developing osteoporosis. (weak recommendation; moderate-quality evidence)
    • 3- Choose treatment options based on assessment of risk and benefit to individual patients. (Strong recommendation; moderate-quality evidence)
    • 4- ACP recommends further research to evaluate treatment of osteoporosis in men and women.
    Ann Intern Med 2008;149:404-415
  • 43. Risk of Afib with Bisphosphonates
    • Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly -Pivotal Fracture Trial (HORIZON)*
    • RCCT: 7765 postmenopausal women with osteoporosis yearly zoledronic acid vs placebo x 3 yrs.
    • Significant reduction in hip and vertebral fractures
    • Increased incidence of Afib classified as serious adverse event ( 1.3% vs 0.4%) P<0.001
    • Overall freq of AF no different in 2 groups (2.4 vs 1.9%)
    • Subsequent HORIZON-Recurrent Fracture Trial failed to find increased AF in treatment group.
  • 44. Rate of AF serious adverse events Horizon-Pivotal Fracture Trial .09% 0.51% Year 3 .17% 0.53% Year 2 .29% 0.47% Year 1 Placebo Zoledronic Acid
  • 45. Association of other Bisphosphonates with AF Risk
    • Fracture Intervention Trial (FIT): RCCT of alendronate in 6459 postmenopausal women. Serious adverse AF events alendronate (1.5%) vs placebo (1.0%) P=.07 NEJM 2007;356:1895-1896.
    • Case control study : More AF patients (719) than controls(966) had ever used alendronate (6.5% vs 4.2%, P=.03) Arch Int Med. 2008;168(8):826-31.
    • Larger case control study in Denmark : No assn of bisphosphonate use with AF in 13,586 patients w/AF and 68,054 controls. (3.2% vs 2.9%) BMJ 2008;336:813-16.
  • 46. Summary
    • Some suggestion of increased AF serious adverse events with bisphosphonate therapy
    • Not a consistent finding
    • Prior RCCT were not designed to examine the occurrence of Afib.
    • Unlikely that there is causal relation between AF and bisphosphonates.
  • 47. Case
    • 68 year old WF calls you saying that her dentist wants to extract a tooth, but he is very concerned because she is on alendronate 70mg weekly. She wants to know your opinion regarding her risk for ONJ.
    • PMH: 2 prior fragility fractures, T score <2.5
    • MEDS: alendronate 70 mg x 8 years
  • 48. ONJ
  • 49. Bisphosphonate Associated ONJ: Definition
    • Current or previous treatment with a bisphosphonate
    • Exposed, necrotic bone in the maxillofacial region > 8 weeks
    • No history of radiation therapy to the jaws
    American Academy of Oral and Maxillofacial Surgeons
  • 50. Case Series 119 patients . J Oral Maxillofac Surg. 2005 Nov;63(11):1567-75
  • 51. Case Series 119 patients J Oral Maxillofac Surg. 2005 Nov;63(11):1567-75
  • 52. Epidemiology
    • Annals systematic review: 368 ONJ patients
      • 84% with multiple myeloma or breast cancer
      • 4% with osteoporosis
      • 60% after dentoalveolar surgery
      • Remaining 40% probably related to infection, denture trauma or other trauma
      • Prevalence of ONJ in cancer patients 6-10%
      • Prevalence in osteoporosis patients unknown
    Ann Intern Med 2006;144:753-761.
  • 53. Epidemiology
    • ASBMR task force review of case reports estimated risk as 1 in 10,000 to 1 in 100,000 patient years of treatment.
    • Post-marketing surveillance
      • Merk: 170 cases/20 million patient years (0.7/100,000patient years)
      • Proctor and Gamble: 1/10,000 patient years
    • RCCTs :
      • No cases of ONJ reported alendronate, risedronate, ibandronate
      • HORIZON: 2 cases (control, and placebo equal)
    • Population based prevalence studies :
      • 3 cases in 780,000 patients receiving bisphosphonates for osteoporosis.
      • <1 in 100,000 patient-years
  • 54. Case
    • Patient later informed you that she underwent procedure without incident. The dentist had drawn “blood-work” which indicated that her risk for ONJ was very low.
  • 55. Bone Turnover Markers as Predictors of Risk?
    • Serum levels of morning fasting C terminal telopeptide (CTX)
    • Based on data from 17 ONJ patients receiving bisphosphonates
      • <100 low risk
      • 100-150 moderate risk
      • >150 high risk
    • Limitations:
      • No controls
      • Reduced markers of resorption expected in patients receiving bisphosphonates
      • Low normal range in healthy women falls within range proposed as high risk.
    J Oral Maxillofac Surgery 2007;65:2397-2410
  • 56. Clinical Application
    • Risk of ONJ <1 in 100,00 patient years in non-cancer patients using bisphosphonate treatment suggests a positive benefit-risk profile.
    • All patients taking bisphosphonates should be informed of the benefits and risks of treatment.
    • Patients taking bisphosphonates should be encouraged to maintain good oral hygeine.
  • 57. Summary
    • Consider screening postmenopausal women and men over 50 at increased risk for osteoporosis
    • Educate patients on universal recommendations
    • Consider treating patients with:
      • Prior fragility fracture
      • T<-2.5
      • Osteopenic patients with elevated risk profile
    • Review risk/benefit profile with all patients
  • 58. Medicare Coverage for BMD Testing
    • Estrogen deficient women at clinical risk
    • Individuals with vertebral abnormalities
    • Individuals receiving or planning to receive long term glucocorticoid therapy
    • Primary hyperparathyroidism
    • To assess response to therapy
  • 59. Screening: Pros and Cons
    • Pros:
      • Common disease with significant morbidity
      • Screening methods available
      • Interventions available to reduce risk
      • Knowledge of risk could improve compliance
    • Cons:
      • Little direct evidence that screening improves outcome.
      • No cutoff value for BMD that delineates fracture risk.
      • Other risk factors may be more important than BMD
      • Cost efficiency issues
      • Knowledge of normal value may hinder compliance
  • 60. Non-FDA Approved Drugs
    • Calcitriol
    • Other bisphosphonates: (etidronate, pamidronate, tiludronate)
    • Parathyroid Hormone (PTH-84)
    • Sodium Flouride
    • Strontium renelate
    • Tibolone
  • 61. Adverse Effects of Drugs
    • Bisphosphonates:
      • Gastrointestinal:
        • Esophageal ulcerations
        • Mild upper GI events (reflux, nausea)
      • Osteonecrosis of the jaw:
      • Atrial fibrillation:
        • Alendronate and zolendronic acid
  • 62. Adverse Effects
    • Estrogen
      • Thromboembolic events
      • Breast cancer (estrogen + progesterone)
    • Teripartide
      • RCCTS  no evidence of serious adverse events
    • SERMs
      • Pulmonary embolism
      • Thromboembolic
    • Calcium and vitamin D
      • RCCTs no clinically important serious adverse events.