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OsteoporosisACOG 2004; 50: 203-16. R4 Osteoporosis Systemic skeletal disease Microarchitectural deterioration of bone tissue with a resultant increase in fragility. 13-18 % of U.S. women over 50 years Another 37-50% have osteopenia Increase the risk of fracture Hip Fx. Morbidity and mortality 15-20% Thoracic spine Fx. Morbidity, including pain Deformity Loss of indepandence Reduce of cardiovascular, respiratory, digestive function. Osteoporosis is a largely preventable complication of menopause.Background Definition Pathophysiology Factors Affecting Bone Mass Screening MethodsDefinitionsAxial skeleton measurement of bone mineral density. Z score or T scores of DXA of lumbar spine or hip.Z score Based of standard deviation from the bone mineral density of a same sex, race, and age.T score Based on the mean peak bone mineral density of a normal young adult population.Definitions 1 SD decrease = 2 fold increase of Fx. Risk Peripheral bone T score Cannot used WHO classification. Used predict of fracture. Osteoporosis screening. In development.Pathophysiology Bone remodeling unit : osteoblast, osteoclast Cycle is divided into 4 phase Take several months to complete Resting Stem cell from BM are attracted to bone surface and differentiate into osteoclasts. Resorption Acid pH mineral dissolve , proteolytic enzymes digest the bone proteins. Reversal Osteoclast cease removing bone. Stem cell attracted to the bone surface, and differentiated into osteoblast. Formation Make new bone with protein matrix(osteoid). Protein matrix accounts for much of tensile strength. Mineral component provides compressional strength. Cytokine (interleukin 1, 3, 6, 11), growth factor, platelet derived GF, IGF-I,II modulate osteoclast and osteoblast function.PathophysiologyBone can be divided into 2 major type Cortical boneOuter shall75% of total bone mass Trabecular boneInternal supportSpongy, interlacing network.25% of total bone massMost of the volume in bone.Because of its larger surface and higher rate of turnover, it shows early bone loss, and first response to therapy.PathophysiologyBone mass peaks at age 30 years 0.4% lost per year after peak. 2% of cortical bone, 5% of trabecular bone loss per year for the 5-8 years after menopause. In recently menopause, excess bone loss is commonly caused by excessive osteoclast-mediated resorption. Later poatmenopausal, suppression of osteoblast activity and inadequate formation of bone play a major role of osteoporosisFactors Affecting Bone Mass Single largest factor is Genetic factor. Family history Caucasian and Asian women Mexican-American African-American Weight-bearing exercise stimulate osteoblastic activity. High dose of corticosteroid(7.5mg) chronic heparin thrapy(12,000-50,000) is associated with bone loss. Hyperthyroidism Factors Affecting Bone MassClinical Considerations and Recommendations When should screening for osteoporosis be initiated? Under what circumstances are screening tests other than DXA useful? Can lifestyle changes prevent osteoporosis and osteoporosis related fracture? Is there a role for estrogen and progestin for the prevention or treatment of osteoporosis? When estrogen therapy is discontinued, how should a woman be monitored for osteoporosis risk? Is other pharmacotherapy beneficial for the prevention and treatment of osteoporosis? Are complementary and alternative therapies beneficial for the prevention of osteoporosis? When should treatment for osteoporosis begin and how should patients be followed?When should screening for osteoporosis be initiated? Guidelines of testing bone mineral density All postmenopausal women aged 65yrs or older. Post menopausal women younger than 65yrs who have 1 or more risk factor All postmenopausal women with fracture to confirm the diagnosis of osteoporosis and determine disease severity. National Osteoporosis Foundation : postmenopausal women aged 50-60 with risk factors or 60-65yrs with or without R/F. Premenopausal women with certain disease or medical conditions For making decision about prevention therapy of early menopausal women. Without new risk factor, not be performed more frequently than every 2 years. Vertebral Fx. order, menopausal women bone mineral density test nonvertebral Fx.(hip or wrist) .Under what circumstances are screening tests other than DXA useful? Peripheral bone densinometry Less expensive, portable, reasonable precision, and low radiation exposure. Screening tools in the evaluation of bone loss, but cannot replace DXA scan for prediction of hip Fx. And the diagnosis of osteoporosis. Quantitative Ultrasonography Provides information on bone elasticity and structure in peripheral sites. Advantage : low cost and lack of radiation. Peripheral Quantitative Computed Tomography Ability to distinguish cortical form trabecular bone. Early and more precise assessment of skeletal change, due to quick change of trabecular bone More expensive and more radiation Less dataUnder what circumstances are screening tests other than DXA useful? Biochemical Makers of Bone Turnover Cannot diagnose osteoporosis, predict bone density or fracture risk. Useful to help identify women with high bone turnover. Assessment of theraputic response (earlier than bone mineral density change) Very expensive.Can lifestyle changes prevent osteoporosis and osteoporosis-related fracture? Weight-bearing exercise stimulate osteoblast to form new bone. Persist only when exercise is continued. For 22 months, 6.1% of bone density of lumbar vertebrae increase observed in postmenopausal women. Disease and sensory impairments that can cause falling should be treated. Medications, living environment should be monitored. Cessation of smoking, reducing alcohol intake Alcohol(7 oz or more per week) increase the risk for both fall and hip fracture and has detrimental effect on bone mineral density. Moderate alcohol is associated with increased mineral bone density. (it is not clear why this occur)Is there a role for estrogen and progestin for the prevention or treatment of osteoporosis? Conjugated equine estrogen(0.625 mg/d) with medroxyprogesterone acetate(2.5 mg/d) reduced the risk of hip and vertebral Fx by 34%, overall Fx by 24%. Lower dose combinations of conjugated equine estrogen(0.3 mg/d) with medroxyprogesterone acetate(2.5 mg/d) increased bone density 3.5-5.2% in postmenopausal(order than 65 yrs). Other study 0.3mg of oral esterified estrogens Transdermal 17B-estradiol 0.025-0.1 mg per day Optimal time to initiate therapy Not determined Believed work best in the first 5-10 years after menopause. A study shows order (mean 76 yrs old) women therapy increased bone density. Therapy discontinued, bone turn over and bone loss accelerated, then approaches that of not treated. Risk of long-term use Increase the risk of cardiovascular and breast cancer.When estrogen therapy is discontinued, how should a woman be monitored for osteoporosis risk?Same as early stage of menopause.Based on age and other risk factorIs other pharmacotherapy beneficial for the prevention and treatment of osteoporosis?2 categories Bisphosphonates (ie, alendronate, risendronate)Inhibit osteoclast activityBoth spine and hipReduce Fx. 30-50%Upper G-I S/E and very poor absorption(less then 1%) Take on empty stomach With only water Remain upright at least 30 min. No additional food or drink during this period. Used when established disease.Is other pharmacotherapy beneficial for the prevention and treatment of osteoporosis? Selective estrogen receptor modulators (SERMs) (ie, raloxifene, tibolone, tamoxifen) Mixed estrogenic and antiestrogenic property depending on tissue. Estrogen like effect on skeleton bone density and to reduce fracture without stimulating endometrial and breast tissue. Raloxifene Reduce 35-50% vertebral Fx. S/E vasomotor symptoms (hot flush, night sweat)- DVT Tibolone Reduce Fx risk Androgenic effect on sexual function Progestational effect on the endometrium. Tamoxifen Used as estrogen receptor positive breast ca. and for chemo prevention of breast ca. Reduce Fx risk . Increase vasomotor Sx. Stimulate endometrium. Incerase venous thrombosisIs other pharmacotherapy beneficial for the prevention and treatment of osteoporosis? Salmon calcitonin is available for osteoporosis treatment. S.C. inj. or nasal spray Reduce lumbar spine Fx(36%) at a dose 200U per day, but did not reduce hip Fx. Reduce bone turnover, but bone density change are small(1 %). Reduce bone pain of osteoporotic compression Fx. S/E : nausea, local inflammation(inj.), flush of face and hands, nasal irritation. Recombinant human PTH Increase trabecular bone density and connentivity. Use in case of failed response to other therapy or very severe disease. Reduce vertebral Fx 53-54%. Expensive and needs daily injection. PTH is significantly reduced when co-administration with bisphosphonates; therefore, they should not be combined. Fluoride increase bone brittleness and propensity to fracture. Testosterone effect is not clear.Is other pharmacotherapy beneficial for the prevention and treatment of osteoporosis? Combinations of Antiresorptive Therapies Addition of progesterones, addition of androgens can have additive effect on bone mineral density. Risedronate, alendronate and raloxifen bone mineral density (1-3%) . fracture protection . Calcium and vit.D should be considered adjuvant therapy for individual.Are complementary and alternative therapies beneficial for the prevention of osteoporosis? Isoflavones (a class of phytoestrogens found in rich supply in soybeans and red clover) studies has not demonstrated a reliable positive effect on bone density, bone turnover marker, or fracture risk in woman with osteoporosisWhen should treatment for osteoporosis begin and how should patients be followed?T score 1 SD decrease = 10-12% change in bone mineral density.Low risk of fracture in young women with osteopenia High cost long term side effect led to suggest withholding treatment until certain theraputic threshold have been reached.The National Osteoporosis Foundation T score -2 without risk factor T score -1.5 with risk factorWhen should treatment for osteoporosis begin and how should patients be followed?Monitoring of treatment requires central bone densinometry. Precision : 2-3% Repeat DXA testing untreated post menopausal per 3-5 yearsTreatment monitor 2 .4-5% mineral density loss .Summary of Recommendations Recommendations based on good and consistent scientific evidence (Level A) Treatment should be initiated to reduce fracture risk in postmenopausal women who have experienced a fragility or low-impact fracture. T scores less than -2 by central DXA in the absence of risk factor and less than -1.5