Comparative Risk of Uveitis with Bisphosphonate Use in Osteoporosis: A Population-Based Cohort Study Using the TriNetX US Database

PURPOSE: To investigate associations between bisphosphonates and uveitis in patients with osteoporosis. METHODS: This population-based retrospective cohort study used de-identified data from the TriNetX US Collaborative Network. Patients with at least two osteoporosis diagnoses between 2013 and 2024 were classified as bisphosphonate users or nonusers. Bisphosphonate users were further stratified according to the presence or absence of autoimmune diseases before treatment initiation. Propensity score matching at a 1:1 ratio was performed to balance baseline characteristics and reduce selection bias. Cox proportional hazards models were used to estimate the risks of overall and subtype-specific uveitis, and Kaplan-Meier analyses were conducted to compare cumulative incidence after matching. RESULTS: Bisphosphonate use was associated with increased risks of overall and anterior uveitis, particularly within the first month of treatment (overall uveitis: hazard ratio [HR], 2.22; 95% CI, 1.50-3.26; anterior uveitis: HR, 2.57; 95% CI, 1.66-3.98). Although the effect estimates decreased over time, the associations remained significant throughout follow-up. Subgroup analyses showed that patients with autoimmune diseases had higher risks of overall uveitis throughout follow-up (HR, 2.26; 95% CI, 2.02-2.54), anterior uveitis (HR, 2.24; 95% CI, 1.98-2.53), and posteriors uveitis (HR, 2.54; 95% CI, 1.91-3.38). CONCLUSION: Bisphosphonate use is associated with an increased risk of uveitis among osteoporosis patients, especially in those with pre-existing autoimmune diseases. Given the widespread use of bisphosphonates in osteoporosis treatment, increased clinician awareness may facilitate early recognition and management of uveitis risk in this population.