Bisphosphonate-Associated Ocular Adverse Events with an Emphasis on Uveitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PURPOSE: This study aims to investigate the risk of developing ocular adverse events, including uveitis, with bisphosphonate use and to analyze the factors that may lead to higher risks of developing the symptoms. MATERIALS & METHODS: A systematic search was conducted across multiple databases, including PubMed, Web of Science, Airiti Library, and Cochrane Library, to identify randomized controlled trials and their post-hoc analyses on bisphosphonate use published before February 2025 that reported ocular adverse events as the primary outcome or in safety analysis. A random-effects meta-analysis was utilized to evaluate the results. Additionally, the impact of different routes of administration and different generations of bisphosphonates on the risk of ocular adverse events were analyzed. The effect estimate was presented with risk ratio. RESULTS: Sixteen studies with a total of 15 062 patients were included in this systematic review. Bisphosphonate use resulted in a significantly higher risk ratio of developing overall ocular adverse events (RR = 1.42, 95% CI = [1.13, 1.80]) and uveitis (RR = 5.94, 95% CI = [1.56, 22.59]) compared to placebo. The overall incidence rate of bisphosphonate-associated ocular adverse events was 2.70%. Among studies specifically reporting uveitis, the incidence rate of uveitis was 1.12%. Additionally, the risk of developing these adverse events was significantly higher within 3 days following intravenous bisphosphonate administration (RR = 3.11, 95% CI = [1.61, 6.00]). CONCLUSIONS: Bisphosphonate use is associated with a significantly higher risk of developing ocular adverse events, including uveitis. The first three days following intravenous bisphosphonate administration are associated with an elevated risk of developing ocular adverse events.