Abstract
Various definitions of nonvertebral fracture have been used in osteoporosis trials, precluding comparisons of efficacy. Using only subgroups of nonvertebral fractures for trial outcomes may underestimate the benefits and costโeffectiveness of treatments. The objectives of this study were to determine (1) the effect of antiresorptive treatment on various nonvertebral fracture outcomes, (2) whether risk reduction from antiresorptive treatment is greater for nonvertebral fractures that have stronger associations with low BMD, and (3) sample size estimates for clinical trials of osteoporosis treatments. Studyโlevel data were combined from five randomized fractureโprevention trials of antiresorptive agents that reduce the risk of nonvertebral fracture in postmenopausal women: alendronate, clodronate, denosumab, lasofoxifene, and zoledronic acid. Pooled effect estimates were calculated with randomโeffects models. The five trials included 30,118 women; 2997 women had at least one nonvertebral fracture. There was no significant heterogeneity between treatments for any outcome (all pโ>โ0.10). Antiresorptive treatment had similar effects on all fractures (summary hazard ratio [HR]โ=โ0.76, 95% CI 0.70โ0.81), highโtrauma fractures (HRโ=โ0.74, 95% CI 0.57โ0.96), lowโtrauma fractures (HRโ=โ0.77, (95% CI 0.71โ0.83), nonvertebral six (ie, hip, pelvis, leg, wrist, humerus, and clavicle) fractures (HRโ=โ0.73, 95% CI 0.66โ0.80), other than nonvertebral six fractures (HRโ=โ0.78, 95% CI 0.70โ0.87), and all fractures other than finger, face, and toe (HRโ=โ0.75, 95% CI 0.70โ0.81). Risk reduction was not greater for fractures with stronger associations with low BMD (pโ=โ0.77). A trial of all nonvertebral fractures would require fewer participants (nโ=โ2641 per arm) than one of a subgroup of six fractures (nโ=โ3289), for example. In summary, antiresorptive treatments reduced all nonvertebral fractures regardless of degree of trauma or special groupings, supporting the use of all nonvertebral fractures as a standard endpoint of osteoporosis trials and the basis for estimating the benefits and costโeffectiveness of treatments. ยฉ 2011 American Society for Bone and Mineral Research