The Efficacy of Bisphosphonates in the Prevention of Vertebral, Hip, and Nonvertebral-Nonhip Fractures in Osteoporosis: A Network Meta-Analysis

Objective To evaluate the efficacy of available bisphosphonate therapies regarding the prevention of vertebral, hip, and nonvertebral-nonhip fractures in postmenopausal women with osteoporosis. Methods Eight randomized placebo controlled trials investigating the effects of zoledronic acid (1 study), alendronate (3), ibandronate (1), risedronate (2), and etidronate (1) in terms of fractures with a follow-up of 3 years (or 2 years if used for registration purposes) were identified with a systematic literature search. The endpoints of interest were morphometric vertebral fractures, hip fractures, and nonvertebral-nonhip fractures. Results of all trials were analyzed simultaneously with a Bayesian network meta-analysis by which the relative treatment effect of 1 intervention to another can be obtained in the absence of head-to-head evidence. Given the estimated treatment effects and their uncertainty, the Bayesian approach allowed for calculations of the probability of which bisphosphonate is best in terms of overall fracture reductions by weighting the impact of each by type of fracture on costs, quality of life, and incidence. Results There is a 79% probability that zoledronic acid shows the greatest reduction in vertebral fractures of all bisphophonates compared. Zoledronic acid showed a relative risk (RR) of 0.30 (95% Credible Interval 0.23-0.37) relative to placebo, an RR of 0.55 (0.41-0.76) relative to alendronate, an RR of 0.50 (0.36-0.70) relative to risedronate, and an RR of 0.58 (0.37-0.92) relative to ibandronate. Regarding hip fractures, there is a 47% probability that zoledronic acid shows the greatest risk reduction, followed by alendronate (36%) and risedronate (11%). RRs of zoledronic acid relative to placebo, alendronate, and risedronate were 0.58 (0.41-0.82), 0.95 (0.54-1.68), and 0.73 (0.37-1.44), respectively. Risedronate showed the greatest reduction in nonvertebral-nonhip fractures, followed by zoledronic acid. The RR of zoledronic acid relative to risedronate was 1.28 (0.87-1.90). Overall, there was a 94% probability that zoledronic acid showed the greatest reduction in any fracture. Weighting the impact of the different type of fractures by incidence, cost, or quality of life showed similar results. Conclusion Of the available bisphosphonates for osteoporosis, zoledronic acid has the highest probability of offering the best overall fracture protection.