Relationship between changes in BMD and nonvertebral fracture incidence associated with risedronate: Reduction in risk of nonvertebral fracture is not related to change in BMD

Introduction: In untreated patients, low BMD correlates with increased fracture risk. Whether greater increases in BMD induced by anti-osteoporosis drugs are related to greater decreases in vertebral fracture risk is controversial, and little has been written about the relationship between change in BMD and nonvertebral fracture risk. We analyzed the relationship between BMD change and nonvertebral fracture incidence using individual patient data from postmenopausal osteoporotic women receiving antiresorptive treatment with risedronate. Materials and Methods: This posthoc analysis combined data from three pivotal risedronate fracture endpoint trials. Women received risedronate 2.5 or 5 mg (n = 2561) or placebo (n = 1418) daily for up to 3 years. BMD and nonvertebral fractures confirmed by radiograph (hip, wrist, pelvis, humerus, clavicle, and leg) were assessed periodically over 3 years. Results: The incidence of nonvertebral fractures in risedronate-treated patients was not different between patients whose spine BMD decreased (7.8%) and those whose spine BMD increased (6.4%; hazard ratio to subgroup of patients who lost BMD [HR], 0.79; 95% CI, 0.50, 1.25) or between those whose femoral neck BMD decreased (7.6%) and those whose femoral neck BMD increased (7.5%; HR, 0.93; 95% CI, 0.68, 1.28). The changes in lumbar spine and femoral neck BMD explained only 12% (95% CI, 2%, 21 %; p = 0.014) and 7% (95% CI, 2%, 13%; p = 0.005), respectively, of risedronate's nonvertebral fracture efficacy. Conclusions: For patients treated with risedronate, changes in BMD as measured by DXA do not predict the degree of reduction in nonvertebral fractures.