Changes in bone mineral density explain little of the reduction in vertebral or nonvertebral fracture risk with anti-resorptive therapy.

The structural basis for the reduction in vertebral and nonvertebral fracture risk in patients using anti-resorptive therapy is not well understood. As reduced bone mineral density (BMD) increases the risk for fracture and anti-resorptive agents increase BMD, it was commonly held that the increase in BMD explained the fracture risk reduction until several meta-analyses either failed to detect a significant association between vertebral fracture risk reduction and the incremental increase in BMD or reported that only a small proportion of the vertebral fracture risk reduction was explained by changes in BMD. Recently, it was reported that the risk of nonvertebral fractures decreased when an increase in BMD accompanied anti-resorptive treatment [J. Clin. Endrocrinol. Metab. 87 (2002) 1586]. However, a reanalysis of the data, using the same statistical methods after correcting for discrepancies in the reported BMD and person-year data, suggested that the magnitude of reductions in nonvertebral fracture risk was not associated with the magnitude of increases in BMD at the end of the first year or at completion of the studies. We infer that only a small proportion of risk reduction in vertebral and nonvertebral fractures observed with anti-resorptive drug therapy is explained by the increase in BMD. Further studies are needed to define the structural basis of the fracture risk reduction.