Abstract
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.
Keywords
hip fracture - total fractures - risk factors - biomarkers - postmenopausal hormone
therapy - bone mineral density
