title: Effects of antiresorptive treatment on nonvertebral fracture outcomes.
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 cost-effectiveness 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. Study-level data were combined from five randomized fracture-prevention 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 random-effects 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 p > 0.10). Antiresorptive treatment had similar effects on all fractures (summary hazard ratio [HR] = 0.76, 95% CI 0.70-0.81), high-trauma fractures (HR = 0.74, 95% CI 0.57-0.96), low-trauma fractures (HR = 0.77, (95% CI 0.71-0.83), nonvertebral six (ie, hip, pelvis, leg, wrist, humerus, and clavicle) fractures (HR = 0.73, 95% CI 0.66-0.80), other than nonvertebral six fractures (HR = 0.78, 95% CI 0.70-0.87), and all fractures other than finger, face, and toe (HR = 0.75, 95% CI 0.70-0.81). Risk reduction was not greater for fractures with stronger associations with low BMD (p = 0.77). A trial of all nonvertebral fractures would require fewer participants (n = 2641 per arm) than one of a subgroup of six fractures (n = 3289), 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 cost-effectiveness of treatments.
authors.affiliation: San Francisco Coordinating Center, California Pacific Medical Center, San Francisco, CA 94107, USA. dmackey@sfcc-cpmc.net
authors.forename: Dawn C
authors.initials: DC
authors.lastname: Mackey
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Black
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Bauer
authors.forename: Eugene V
authors.initials: EV
authors.lastname: McCloskey
authors.forename: Richard
authors.initials: R
authors.lastname: Eastell
authors.forename: Peter
authors.initials: P
authors.lastname: Mesenbrink
authors.forename: John R
authors.initials: JR
authors.lastname: Thompson
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001862:Bone Resorption / Q000188:drug therapy*; D005260:Female; D050723:Fractures, Bone / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged
chemical_list: D050071:Bone Density Conservation Agents