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Treatment of Postmenoapausal Osteoporosis

Treatment of Postmenoapausal Osteoporosis. What is Osteoporosis. A disease that causes bones to lose mass, weaken and fracture affects 75 million people in Europe, Japan and the United States (over 28 million Americans) 1:2 women and 1:8 men are affected progression is slow, silent, painless.

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Treatment of Postmenoapausal Osteoporosis

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  1. Treatment ofPostmenoapausalOsteoporosis medslides.com

  2. What is Osteoporosis • A disease that causes bones to lose mass, weaken and fracture • affects 75 million people in Europe, Japan and the United States (over 28 million Americans) • 1:2 women and 1:8 men are affected • progression is slow, silent, painless medslides.com

  3. Osteoporosis - definition “a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration with a consequent increase in bone fragility and susceptibility to fracture” Consensus Development Conference Osteoporosis Int 1997;7:1-6 medslides.com

  4. Osteoporosis - definition “a bone mineral density (T score) that is 2.5 SD below the mean peak value in young adults” Working Group of the W.H.O. • useful for research but limited in clinical use • ignores other determinants of bone strength • ignores higher risk of fracture in older women • failed to specify technique and site of measurement J Bone Miner Res 1994; 9:1137-41 medslides.com

  5. Bone mineral densityZ Score • Z score - a comparison with the mean value in normal subjects of the same age and sex (either at the lumbar spine or the proximal femur) • Z score below -1 (lowest 25%)risk of fracture is approx doubled • Z score below -2 (lowest 2.5%)risk of fracture is even higher N Engl J Med 1998;338:736-746 medslides.com

  6. Bone Development • Bones build mass beginning at birth and peaks by age 20-30 • bone growth promoted by adequate intake of calcium, vitamin D, and exercise • bone begin to lose mass after age 30 medslides.com

  7. Building Strong Bones • Adequate calcium intake • teenagers and postmenopasal women not taking estrogen need 1,500 mg of calcium per day • other adults need 1,000 mg per day • Vitamin D • Adequate exercise medslides.com

  8. Osteoporosisclinical risk factors • Female gender • Caucasian or Asian race • Thin body build • Late onset of menstrual periods • Early onset menopause • Caffeine, Cigarettes and Alcohol • A family history of osteoporosis medslides.com

  9. Osteoporosisclinical risk factors National Osteroporosis Foundation • low body weight (<58 kg) • current smoking • first-degree relative with low-trauma fracture • personal history of low-trauma fracture Osteoporosis Int (in press) N Engl J Med 1998;338:736-746 medslides.com

  10. Osteoporosis - Risk factors • Genetic factor • first-degree relative with low-trauma fracture • Environmental factors • cigarette smoking • alcohol abuse • physical inactivity • thin habitus • diet low in calcium • little exposure to sunlight N Engl J Med 1998;338:736-746 medslides.com

  11. Osteoporosis - Risk factors • Menstral status • early menopause (before the age of 45 years) • previous amenorrhea (e.g., due to anorexia nervosa, hyperprolactinemia) • Drug therapy • glucocorticoids (  7.5 mg/day for > 6 months) • antiepileptic drugs (e.g., phenytoin) • excessive substitution therapy (e.g., thyroxine) • anticoagulant drugs (e.g., heparin, warfarin) N Engl J Med 1998;338:736-746 medslides.com

  12. Osteoporosis - Risk factors • Endocrine disease • primary hyperparathryroidism • thyrotoxicosis • Cushing’s syndrome • Addison’s disease • Rheumatologic diseases • rheumatoid arthritis • ankylosing spondylitis N Engl J Med 1998;338:736-746 medslides.com

  13. Osteoporosis - Risk factors • Hematologic disease • myltiple myeloma • systemic mastocytosis • lymphoma, leukemia • pernicious anemia • Gastrointestinal diseases • malabsorption syndromes (e.g., celiac disease, Crohn’s disease, surgery for peptic ulcer) • chronic liver disease (primary biliary cirrhosis) N Engl J Med 1998;338:736-746 medslides.com

  14. Diagnostic Evaluation bone mineral density • indications: • in women with strong risk factors(see slides 10-13) • in those with osteoporosis-related fractures (wrist, spine. Proximal femur, or humerus after mild or moderate trauma) N Engl J Med 1998;338:736-746 medslides.com

  15. Diagnostic Evaluation bone mineral density • techniques: • dual-energy x-ray absorptiometry (DEXA) • proximal femur is most useful for predicting fractures • lumbar spine is most useful for monitoring therapy • single-energy x-ray absorptiometry • quantitative computed tomography • ultrasonography N Engl J Med 1998;338:736-746 medslides.com

  16. Diagnostic Evaluation bone mineral density • Diagnosis and treatment • T score < -2.5need treatment to prevent fractures • T score < -2 ( at any site)indicates accelerated bone lossneed to identify major risk factor • T score < -1 (lumbar spine or prox femur) need to prevent further bone loss N Engl J Med 1998;338:736-746 medslides.com

  17. Diagnostic Evaluation biochemical markers • Bone formation • serum alkaline phosphatase • serum ostocalcin • serum C- and N-propeptides of type I collagen N Engl J Med 1998;338:736-746 medslides.com

  18. Diagnostic Evaluation biochemical markers • Bone resorption • urinary excretion of • pyridium cross-links of collagen (deoxypyridinoline) • C- and N-telopeptides of collagen • galactosyl hydroxylysine • hydroxyproline • serum tartrate-resistant acid phosphatase N Engl J Med 1998;338:736-746 medslides.com

  19. Pathophysiology remodeling space • space where some bone has been resorbed but not yet replaced during the remodeling process • remodeling space is increased in postmenopausal osteoporosis N Engl J Med 1998;338:736-746 medslides.com

  20. Pathophysiology remodeling space • differential effects • cancellous-bone loss • estrogen deficiency • glucocorticoid therapy • cortical bone loss • parathyroid hormone excess N Engl J Med 1998;338:736-746 medslides.com

  21. antiresorptive drugs • antiresorptive drugs (estrogen, bisphosphonates, calcitonin)  both the rates of bone resorption (in weeks) and formation (in months) • bone mineral density is  by 5-10 % for the first 2-3 years then plateaus; this reduces the risk of fracture by 50% N Engl J Med 1998;338:736-746 medslides.com

  22. Bone formation drugs • sodium fluoride and intermittent parathyroid hormone • stimulate bone formation • overfill resorption cavities • the increase in bone density continues beyond two years N Engl J Med 1998;338:736-746 medslides.com

  23. Effective of Drug Therapy onLumbar-Spine Bone Marrow Density 1.2 Bone Formation drug 1.1 Lumbar-Spine Bone Mineral Density (g/cm2) Antiresorptive drug 1.0 Placebo 0.9 -1 0 1 2 3 4 Year N Engl J Med 1998;338:736-746 medslides.com

  24. Risk Factors for Bone Fracture •  bone marrow density (BMD) • high rate of bone turnover - the site of remodeling can break • type of drug therapy - e.g., sodium fluoride increases BMD, but weakens the bone by being incorporated into the hydroxyapatite crystals of bone N Engl J Med 1998;338:736-746 medslides.com

  25. Effects of Therapy on Lumbar-Spine BMD and Rate of Vertebral Fracture 14 12 10 8 Relative Risk of Vertebral Fracture 6 4 Sodium fluoride Alendronate 2 Estradioal 0 -4 -3 -2 -1 0 1 2Lumbar-Spine Bone Mineral Density N Engl J Med 1998;338:736-746 medslides.com

  26. Current Therapiesestrogen-replacement • Benefits • relief of menopausal symptoms • prevention of bone loss and fractures • increase in bone marrow density • decrease in bone turn over • lower relative risk (0.39) for vertebral fracture • prevention of ischemic heart disease • prevention of dementia N Engl J Med 1998;338:736-746 medslides.com

  27. Current Therapiesestrogen-replacement • Risks • return of menstrual bleeding • risk of endometrial carcinoma • breast tenderness • risk of breast carcinoma • migraine • risk of DVT and pulmonary embolism N Engl J Med 1998;338:736-746 medslides.com

  28. Current Therapiesbiphosphonates • Stable analogues of pyrophosphate • poorly absorbed from the intestine (<10%), must not be taken with food • deposited in bone at the site of mineralization; apparently causing the death of osteoclasts which results in decreased bone resorption N Engl J Med 1998;338:736-746 medslides.com

  29. Current Therapiesbiphosphonates Etidronatelow dose intermittent therapy: 400 mg /day x 2 wks, followed by 500 mg supplemental calcium per day x 11 wks • increase in BMD of 4-8% in lumbar spine and 2% in femoral neck in 3 yrs • decrease in vertebral fracture rate N Engl J Med 1998;338:736-746 medslides.com

  30. Current Therapiesbiphosphonates Alendronate10 mg per day • increase in BMD of 8.8% in lumbar spine and 5.9% in femoral neck in 3 yrs • 48% relative decrease in new fractures and height loss • associated with erosive esophagitis N Engl J Med 1998;338:736-746 medslides.com

  31. Current Therapiesbiphosphonates Alendronate • to minimize the risk of esophagitis -take with a glass of water while upright at least 30 minutes before breakfast • absolute contraindications: achalasia, esophageal strictures • relative contraindications: reflux disease N Engl J Med 1998;338:736-746 medslides.com

  32. Current Therapiescalcium and vitamin D • French Study • 3270 institutionalized women • treated with calcium (1200 mg per day) and vitamin D (800 IU per day) for 3 yrs • risk of hip fracture was reduced by 30% • reversal of secondary hyperparathyroidism • increase in BMD of the femoral neck BMJ 1994;308:1081-2 medslides.com

  33. Current Therapiescalcium and vitamin D • Dutch Study • 2578 elderly women • treated with vitamin D (400 IU per day)but no supplemental calcium • rate of hip fracture unchanged compared to placebo • comment: the women were not housebound Ann Intern Med 1996;124:400-6 medslides.com

  34. Current Therapiescalcium and vitamin D • U.S. Study • 389 men and women over age >63 • treated with calcium (500 mg per day) and vitamin D (700 IU per day) • decreased rate of nonvertebral fractures with only a small increase in BMD of the lumbar spine (0.9%), femoral neck (1.2%), and total body (1.2%) N Engl J Med 1997;337:70-6 medslides.com

  35. Current Therapiescalcitonin • a 32-amino-acid peptide produced by the thyroid C cells • inhibits the action of ostoclasts • decreases bone resorption N Engl J Med 1997;337:70-6 medslides.com

  36. Current Therapiescalcitonin • Salmon or human calcitonin • 100 IU daily, subcutaneous or intramuscular • 200 IU daily, intranasal (salmon calcitonin) • suppositories are weak and poorly tolerated • Benefits • increase BMD, decrease vertebral fracture • Side effects • nausea, flushing, diarrhea, nasal discomfort N Engl J Med 1997;337:70-6 medslides.com

  37. Current Therapiesfluoride Fluoride & Vertebral Osteoporosis Study • 354 women with osteoporosis • 2 year trial of sodium fluoride (50 mg/d) vs placebo • significant increase in lumbar-spine BMD (10.8% vs 2.4%), but no effect on the rate of vertebral fracture Ostoporosis Int (in press) N Engl J Med 1997;337:70-6 medslides.com

  38. Future Treatments • Estrogen-receptor modulators • has mixed estrogen-agonist and estrogen-antagonist activity • raloxifene * shown to decrease bone resorption and increase BMD in the lumbar-spine (2.4%), hip (2.4%), and body (2.0%) • Others: tamoxifen, drolxifene, levormeloxifene J Bone Miner Res 1996;11:835-42 medslides.com

  39. Future Treatments • Parathyroid Hormone • daily injections stimulate bone formation • increase in BMD of the spine • effects on fracture rate not yet known • Vitamin D analogues • strontium salts • ipriflavone J Clin Endocrinol Metab 1997;82:620-8 medslides.com

  40. ConclusionsTherapeutic Choices • Women most at risk should be treated • fracture with minimal or no trauma • those with low bone marrow density • Acute phase of vertebral fracture • manage with analgesic drugs • lumbar-support corset • short period of bed rest and calcitonin N Engl J Med 1997;337:70-6 medslides.com

  41. ConclusionsTherapeutic Choices • Life style change • avoid heavy lifting • encourage exercise (such as walking) • avoid sedative drugs (may cause falls) • calcium intake increase to 1500 mg / day • avoid tobacco and excess alcohol • hip protectors (poor compliance) N Engl J Med 1997;337:70-6 medslides.com

  42. ConclusionsTherapeutic Choices • first choice: • estrogen-replacement therapy should be given for at least 5 years • use preparation that do not cause uterine bleed (continuous combined estro-progest) • alternative choice: • biphosphonates (avoid SE of estrogen) • vitamin D for housebound patients N Engl J Med 1997;337:70-6 medslides.com

  43. ConclusionsTherapeutic Goal • to halve the risk of fracture • a new fracture should not be considered a set back • patients should be encouraged to continue therapy N Engl J Med 1997;337:70-6 medslides.com

  44. References • Treatment of Postmenopausal Osteoporosis.Richard Eastell, MD. N Engl J Med 1998;338:736-746 • Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women.Chapuy MC et al. BMJ 1994;308:1081-2 • Vitamin D supplementation and fracture incidence inelderly persons. Lips P et al. Ann Inern Med 1996;124:400-6 medslides.com

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