Comparative efficacy of bisphosphonates in short-term fracture prevention for primary osteoporosis: a systematic review with network meta-analyses

Our network meta-analyses compared the efficacy of different bisphosphonates preventing fractures for primary osteoporosis. By including 36 studies, we found that zoledronic acid seemed the most effective in preventing vertebral fracture, nonvertebral fracture, and any fracture, and alendronate or zoledronic acid seemed the most effective in preventing hip fracture. Introduction This study was conducted in order to analyze the available evidence on the efficacy of bisphosphonates for preventing fractures. Methods We considered randomized trials comparing any bisphosphonate with other bisphosphonate or placebo. We searched Cochrane Library, Embase, and PubMed and manually searched reference list of relevant articles. Pairwise and network meta-analyses were performed. The primary outcome is vertebral fracture. Secondary outcomes include nonvertebral fracture, hip fracture, wrist fracture, and any fracture. Results Thirty-six studies were included. Significant difference was found between bisphosphonates for vertebral fracture and nonvertebral fracture (P < 0.0001 and P = 0.04, respectively). Compared with placebo, alendronate, clodronate, ibandronate, minodronate, pamidronate, risedronate, and zoledronic acid significantly prevented vertebral fracture. Zoledronic acid significantly reduced the risk of vertebral fracture, compared with alendronate, clodronate, etidronate, ibandronate, risedronate, and tiludronate (0.65 (0.46, 0.91), 0.53 (0.33, 0.86), 0.45 (0.27, 0.74), 0.52 (0.36, 0.75), 0.59 (0.42, 0.83), and 0.31 (0.21, 0.48), respectively). Compared with etidronate, clodronate and zoledronic acid significantly prevented nonvertebral fracture. Compared with alendronate, zoledronic acid significantly prevented any fracture. The possibility rankings showed that zoledronic ranked first in preventing vertebral fracture, hip fracture, and any fracture, and pamidronate ranked first in preventing nonvertebral fracture and wrist fracture. In the sensitivity analyses, zoledronic acid ranked first in preventing nonvertebral fracture, and alendronate ranked first in preventing hip fracture and wrist fracture. Conclusion Zoledronic acid seemed the most effective in preventing vertebral fracture, nonvertebral fracture, and any fracture, and alendronate or zoledronic acid seemed the most effective in preventing hip fracture. Uncertainty still remains and future studies are needed to accurately evaluate the comparative efficacy of bisphosphonates.