Your SlideShare is downloading. ×

Update: Osteoporosis

2,036

Published on

0 Comments
2 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
2,036
On Slideshare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
102
Comments
0
Likes
2
Embeds 0
No embeds

Report content
Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
No notes for slide
  • 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.
  • 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.

    ×