Insights into the Epidemiology of Postmenopausal Osteoporosis: The Women's Health Initiative

Osteoporosis and its associated increased risk for fragility fracture is one of the Most disabling consequences of aging in women. To successfully reduce the public health burden of this pervasive disease, it is necessary to develop strategies that permit the earlier identification of women at risk for fracture and ensure that preventive interventions to reduce the risk for fracture are both safe and effective. The Women's Health Initiative offers the unprecedented opportunity to systematically address both of these issues. Eleven clinically available risk factors (age, race/ethnicity, self-reported health, weight, height, physical, activity, parental hip fracture, fracture history after age 54, current smoking, corticosteroid use, and history of treated diabetes), have been identified to predict 5-year hip fracture risk in white women. Two of these factors (age and fracture history) also predict risk for total fractures in women irrespective of race-ethnicity. Biomarkers including low vitamin D or bioavailable testosterone and/or high cystatin C, pro-inflammatory cytokines, Osteoprotegerin and sex hormone-binding globulin also predict risk for hip fracture independent of clinical risk factors. Two cornerstones of therapy for postmenopausal osteoporosis-postmenopausal hormone therapy and calcium plus vitamin D supplementation-were rigorously studied. Estrogen with or without a progestin was effective at preventing bone loss and reducing risk for hip, Clinical Vertebral and total fractures but the balance of risks and benefits failed to show an overall benefit of taking estrogen-alone or estrogen plus progestin as a preventive strategy for skeletal health. Calcium plus vitamin D supplementation also demonstrated a small but significant favorable effect on hip bone density but in contrast, the Modest effect did not translate into a significant reduction in the risk of fractures in intent-to-treat analyses. Data such as these have helped to lay a foundation for the more effective management of postmenopausal osteoporosis.