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Long-term Management of Osteoporosis March 25, 2013

Long-term Management of Osteoporosis March 25, 2013. Ronald C. Hamdy , MD, FRCP, FACP Professor of Medicine Cecile Cox Quillen Chair of Geriatric Medicine Director, Osteoporosis Center East Tennessee State University. R. C. Hamdy - Disclosures.

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Long-term Management of Osteoporosis March 25, 2013

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  1. Long-term Management of OsteoporosisMarch 25, 2013 Ronald C. Hamdy, MD, FRCP, FACP Professor of Medicine Cecile Cox Quillen Chair of Geriatric Medicine Director, Osteoporosis Center East Tennessee State University

  2. R. C. Hamdy - Disclosures

  3. Long-term Management of OsteoporosisMarch 25, 2013 • OBJECTIVES • Evaluate the risk/benefit of long-term therapy for osteoporosis • Develop a long-term management strategy tailored to the individual circumstances of the patient. • Recognize the possible long-term complications of medications commonly used for osteoporosis

  4. Mrs. DA, 68 years old WW- OsteoporosisOn alendronate for about 12 years • Taking the medication as directed • Pain in left thigh, 6 weeks: 6/10 not constant, gradually worse precipitated by exertion, especially jogging partly relieved by rest & local heat now, often wakes her at night. Starting to interfere with daily activities

  5. Mrs. DA, 68 years old WW- OsteoporosisOn alendronate for about 12 years • 12 years ago: T-score -2.9 lumbar vertebrae • Surgical menopause at age 32, no HRT • Family history: positive, mother fragility hip fracture • Good dietary calcium and vitamin D intake • Physically active lifestyle, exercises regularly: daily jogging, twice weekly: aerobic/resistive exercises • Medication: alendronate calcium/vitamin D supplements

  6. Mrs. DA, 68 years old WW- OsteoporosisOn alendronate for about 12 years • Weight 152 pounds, steady; height 64” • No kyphosis • Tenderness to deep palpation upper 1/3 left femur • Pain worse when she stands on left leg • Good range of movement both hips • No pain on passively moving both hips • Leg raising test negative, both sides • No evidence of arthritis • No evidence of neurologic deficits

  7. Mrs. DA, 68 years old WW- OsteoporosisOn alendronate for about 12 years • Weight 152 pounds, steady; height 64” • No kyphosis • Tenderness to deep palpation upper 1/3 left femur • Pain worse when she stands on left leg • Good range of movement both hips • No pain on passively moving both hips • Leg raising test negative, both sides • No evidence of arthritis • No evidence of neurologic deficits

  8. Hamdy, RC, Lewiecki, EM. Osteoporosis: Oxford University Press, 2013

  9. Warning sign: Impending fracture Hamdy, RC, Lewiecki, EM. Osteoporosis: Oxford University Press, 2013

  10. Prevention is better than cure Hamdy, RC, Lewiecki, EM. Osteoporosis: Oxford University Press, 2013

  11. Rod inserted prophylactically Hamdy, RC, Lewiecki, EM. Osteoporosis: Oxford University Press, 2013

  12. Reports of femoral shaft fractures occurring in patients on bisphosphonate therapy.

  13. Reports of femoral shaft fractures occurring in patients on bisphosphonate therapy. Atypical femoral shaft fractures

  14. Femoral Shaft Fractures Fractures occurring anywhere between the lesser trochanter and the supracondylar flare.

  15. Femoral Shaft Fractures • 7 to 10% of all femoral shaft fractures • Bimodal age distribution

  16. Femoral Shaft Fractures • 7 to 10% of all femoral shaft fractures • Bimodal age distribution • 75% due to severe trauma • Usually good prognosis

  17. Femoral Shaft Fractures • 7 to 10% of all femoral shaft fractures • Bimodal age distribution • 75% due to severe trauma • Usually good prognosis • 25% due to low trauma or no trauma

  18. Femoral Shaft Fractures • 7 to 10% of all femoral shaft fractures • Bimodal age distribution • 75% due to severe trauma • Usually good prognosis • 25% due to low trauma or no trauma • Osteoporosis • More frequent in women than men • Poor prognosis • Mortality: 14% first year, 25% second year • 50% do not achieve pre-fracture level • 71% need alternative accommodation

  19. Femoral Shaft Fractures • 7 to 10% of all femoral shaft fractures • Bimodal age distribution • 75% due to severe trauma • Usually good prognosis • 25% due to low trauma or no trauma • Osteoporosis • More frequent in women than men • Poor prognosis • Mortality: 14% first year, 25% second year • 50% do not achieve pre-fracture level • 71% need alternative accommodation

  20. Femoral Shaft Fractures Typical: underlying osteoporosis v/s Atypical: osteoporosis treatment

  21. Atypical Femoral Shaft Fractures ASBMR Task Force - Major Features Between lesser trochanter & supracondylar flare • No/minimal trauma • Unilateral or bilateral • Complete or incomplete Non-comminuted Short transverse or oblique configuration Medial spike Shane E, et al. JBMR 2010;25:2267-2294

  22. Atypical Femoral Shaft Fractures ASBMR Task Force - Minor Features • Prodromal symptoms • Localized pain • Localized bone tenderness • Imaging studies • Insufficiency/stress fractures • Localized periosteal reaction • Localized increased Technetium uptake • Other morbidities Shane E, et al. JBMR 2010;25:2267-2294 Hamdy, RC, Lewiecki, EM. Osteoporosis: Oxford University Press, 2013

  23. Basic Science Considerations Bisphosphonates Prevent Bone Loss Increase Bone Mass Reduced Bone Resorption Reduced Fracture Risk

  24. Basic Science Considerations Bisphosphonates Prevent Bone Loss Increase Bone Mass Reduced Bone Resorption Increased Mature Cross-Links Micro-damage AGE Products Reduced Fracture Risk

  25. Basic Science Considerations Bisphosphonates Prevent Bone Loss Increase Bone Mass Reduced Bone Resorption Increased Mature Cross-Links Micro-damage AGE Products Micro-architectural Deterioration Reduced Fracture Risk

  26. Basic Science Considerations Bisphosphonates Prevent Bone Loss Increase Bone Mass Reduced Bone Resorption Increased Mature Cross-Links Micro-damage AGE Products Micro-architectural Deterioration Increased Bone Brittleness Reduced Fracture Risk

  27. Basic Science Considerations Bisphosphonates Prevent Bone Loss Increase Bone Mass Reduced Bone Resorption Increased Mature Cross-Links Micro-damage AGE Products Micro-architectural Deterioration Increased Bone Brittleness Reduced Fracture Risk Stress Fractures

  28. Basic Science Considerations Bisphosphonates Prevent Bone Loss Increase Bone Mass Reduced Bone Resorption Increased Mature Cross-Links Micro-damage AGE Products Micro-architectural Deterioration Increased Bone Brittleness Reduced Fracture Risk Atypical Femoral Shaft Fractures Stress Fractures

  29. Basic Science Considerations Bisphosphonates Prevent Bone Loss Increase Bone Mass Reduced Bone Resorption Increased Mature Cross-Links Micro-damage AGE Products Micro-architectural Deterioration Increased Bone Brittleness Impaired Healing Process Reduced Fracture Risk Atypical Femoral Shaft Fractures Stress Fractures

  30. Basic Science Considerations Bisphosphonates Prevent Bone Loss Increase Bone Mass Reduced Bone Resorption Reduced Bone Angiogenesis Increased Mature Cross-Links Micro-damage AGE Products Micro-architectural Deterioration Increased Bone Brittleness Impaired Healing Process Reduced Fracture Risk Atypical Femoral Shaft Fractures Stress Fractures

  31. Atypical Femoral Shaft Fractures Bisphosphonate Therapy • Bisphosphonates: • 2004: 57 million prescriptions in USA • 2007: 225 million prescriptions worldwide • Largest case series of Atypical Femoral Shaft Fractures: • 320: Shane et al, 2010 • 141: Giusti et al, 2010

  32. Placebo-controlled Studies • Double-blind, randomized, prospective studies Alendronate 2,027 Risedronate 5,445 + 2,458 + 1,116 Ibandronate 2,946 Zoledronic acid 7,736 Denosumab 7,736 • Extension studies No increased risk • Re-analysis of data including extension studies No increased risk* *Black DM et al. NEJM 2010;362(19):1761-71

  33. Retrospective Population Studies Danish registry-based cohort study: 11,944 subjects > 60 years 2-matched cohorts: • 5,187 • 10,374 Patients with FSF were not more likely than patients with hip fractures to be on alendronate, but more patients were on corticosteroids. Abrahamsen B, et al. JBMR 2009;24:1095-1102

  34. Retrospective Population Studies Positive effect of bisphosphonates on FSF Higher reduction of FSF in patients highly compliant with bisphosphonate therapy. • Abrahamsen B, et al. Subtrochanteric and diaphyseal femur fractures in patients treated with alendronate: a register-based national cohort study. JBMR 2009; 24(6):1095-102. • Hsiao FY, et al. Hip and subtrochanteric or diaphyseal femoral fractures in alendronate users: a 10-year, nationwide retrospective cohort study in Taiwanese women. ClinTher. 2011;33(11):1659-67.

  35. ASBMR Task ForceAtypical Femoral Shaft Fractures& Anti-resorptive Therapy A causal relationship between bisphosphonates and femoral shaft fractures could not be established. ASBMR Task Force. JBMR 2010;25:2267-2294

  36. Atypical Femoral Shaft Fractures& Anti-resorptive Therapy Over-use, or over-dose not adverse effect

  37. Atypical Femoral Shaft Fractures& Anti-resorptive Therapy Over-use, or over-dose not adverse effect Often can be anticipated

  38. Femoral Fractures per 100,000National Hospital Discharge Survey & MarketScan® 1996-2006 Nieves JW, et al OsteoporosInt 2010;21(3):399-408

  39. Femoral Fractures per 100,000National Hospital Discharge Survey & MarketScan® 1996-2006 Let’s be vigilant, but not stop positive effects of therapy Nieves JW, et al OsteoporosInt 2010;21(3):399-408

  40. Mrs. BD, 68 years old WW- Osteoporosis • T-score -2.7, left femoral neck • Post surgical menopause at age 34 years, no HRT • Positive family history: mother fragility hip fracture • Good daily calcium and vitamin D intake • No excessive sodium/caffeine intake • Exercies regularly: aerobic/resistive exercises • No medications • No secondary causes

  41. Mrs. BD, 68 years old WW- Osteoporosis • Refuses bisphosphonates Concerned about Atypical femoral shaft fractures

  42. Mrs. BD, 68 years old WW- Osteoporosis • Refuses bisphosphonates Concerned about Atypical femoral shaft fractures • Probability of sustaining: Atypical femoral shaft fracture 1:10,000 to 1:20,000

  43. Mrs. BD, 68 years old WW- Osteoporosis • Refuses bisphosphonates Concerned about Atypical femoral shaft fractures • Probability of sustaining: Atypical femoral shaft fracture 1:10,000 to 1:20,000 Osteoporotic fracture Hip # 33% 1:3 Other # 50% 1:2

  44. Mrs. OJ, 68 years old WW- Osteoporosis • Has been on oral bisphosphonates for about 12 years • Taking them as directed, no adverse effects • Dentist concerned about impending tooth extraction

  45. Mrs. OJ, 68 years old WW- Osteoporosis • Natural menopause at age 47 years, no HRT • Positive family history: mother fragility hip fracture • Daily dietary calcium intake about 1,200 mg • No excessive sodium/caffeine intake • Exercies regularly: aerobic/resistive exercises • No medications, except alendronate

  46. Mrs. OJ, 68 years old WW- Osteoporosis • Should bisphosphonates be discontinued? • What else can be done to prevent Osteonecrosis of the jaw?

  47. Necrotic tissue removed, Larger cavity left, lined by injured bone Tooth to be extracted Cavity left after tooth extraction Some of injured bone: recovers Undergoes necrosis Osteo-necrosis of the jaw

  48. Tooth to be extracted Cavity lined by injured bone Cavity left after tooth extraction Some of injured bone: recovers Undergoes necrosis Osteo-necrosis of the jaw

  49. Tooth to be extracted Cavity lined by injured bone Osteoclasts remove injured bone Cavity left after tooth extraction Some of injured bone: recovers Undergoes necrosis Osteo-necrosis of the jaw

  50. Tooth to be extracted Cavity lined by injured bone Osteoclasts remove injured bone Access denied Cavity left after tooth extraction Some of injured bone: recovers Undergoes necrosis Osteo-necrosis of the jaw

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