Is bone mineral density predictive of fracture risk reduction?

SUMMARY Bone mineral density (BMD) measurement is a widely available noninvasive means of identifying individuals with osteoporosis and, possibly, those at high risk for fracture. This nonsystematic review examines the relationship between BMD increase and fracture risk reduction in clinical trials evaluating osteoporosis therapy. The trials examined here are predominantly in postmenopausal women. BMD increase correlates poorly with fracture risk reduction in clinical trials of osteoporosis therapy conducted in postmenopausal women. Although BMD may increase with therapy, the increase is not measurable until later, and the overall increase is too small to account for the timing and magnitude of fracture risk reduction. BMD is only one of many contributors to bone strength and fracture risk reduction. Bone strength is derived from bone quantity, which consists of density and size, and bone quality, which, in turn, consists of structure (micro- and macroarchitecture), material properties, and turnover. Data are beginning to accrue suggesting that changes in bone turnover markers may be an accurate predictor of fracture risk reduction. Future research will elucidate the link between changes in bone turnover markers and bone architecture as a measure of osteoporosis treatment efficacy. Until then, physicians will continue to rely on fracture risk reduction data from well-designed clinical trials when judging the efficacy of different treatments for osteoporosis.