The purpose of this study was to estimate the benefits and drawbacks of bisphosphonates in the treatment of osteoporosis and osteopenia in middle-aged and elderly individuals.

We searched Ovid MEDLINE, Embase, the Web of Science, and Cochrane library databases for randomized clinical trials (RCTs) evaluating the effects of bisphosphonates and performed a network meta-analysis to summarize the direct and indirect evidence on the efficacy and safety of bisphosphonate therapy in middle-aged and elderly individuals with osteoporosis or osteopenia.

A total of 14 RCTs (7, 769 patients with osteoporosis or osteopenia; median age, 67 years; median follow-up, 27 months) were included in this network meta-analysis. Of these, 8, 10, 9, and 6 RCTs provided outcomes on bone mineral density changes, clinical fracture rates, vertebral fracture rates, and nonvertebral fracture rates, respectively. Regarding the primary efficacy outcome, there was a 97% probability for alendronate to be the most effective treatment approach for increasing bone mineral density and an 84% probability for zoledronate to be the most effective treatment approach for clinical fractures. Regarding vertebral fractures and safety outcomes, zoledronate showed an odds ratio (OR) of 0.45 (95% confidence intervals [CI], 0.30–0.69) relative to placebo. For nonvertebral fractures, the OR of zoledronate relative to placebo was 0.51 (95% CI 0.29–0.90).

This study revealed that alendronate was effective in increasing bone mineral density in middle-aged individuals and that zoledronate was a safe treatment option for osteoporosis and osteopenia, conferring a low incidence of fracture. However, further clinical studies are needed to confirm these results.