(C-001) Denosumab Use and Cataract Risk in Patients with Osteoporosis: A Propensity Score-matched Cohort Study

Background: Cataracts and osteoporosis are common conditions in older adults, with emerging evidence suggesting a potential link between the two through shared physiological mechanisms such as calcium metabolism dysregulation and hormonal imbalances. Recent studies have suggested that denosumab, a commonly used anti-osteoporosis drug, may lower cataract risk; however, relevant evidence remains limited and requires further investigation.

Objectives: This study aimed to evaluate the association between denosumab use and the risk of developing cataracts in patients with osteoporosis.

Methods: We conducted a retrospective cohort study using the TriNetX Analytics Network, which includes electronic health records from 64 healthcare organizations in the United States. Adults with osteoporosis who initiated denosumab or zoledronic acid between January 2010 and June 2024 were included. Zoledronic acid was used as an active comparator because both drugs have similar prescription indications in Taiwan. Patients with prior cataract diagnoses, an estimated glomerular filtration rate (eGFR) ≤30 mL/min, or prior bisphosphonate or denosumab use were excluded. Propensity score matching was applied to balance baseline characteristics between treatment groups, including age, sex, race, comorbidities, baseline medication use, and relevant laboratory test results. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident cataracts. Subgroup analyses were conducted based on age and sex.

Results: After propensity score matching, 14,856 patients receiving denosumab and 14,856 receiving zoledronic acid were included. The denosumab group had a significantly lower risk of developing cataracts compared to the zoledronic acid group (HR: 0.807; 95% CI: 0.731–0.890). Subgroup analyses showed that denosumab use was associated with a significantly reduced cataract risk in both men (HR: 0.692; 95% CI: 0.496–0.967) and women (HR: 0.755; 95% CI: 0.672–0.848). A lower cataract risk with denosumab was also observed in individuals aged ≥65 years (HR: 0.788; 95% CI: 0.652–0.953), while no significant difference was found in those aged < 65 years.

Conclusions: This study suggests that denosumab use is associated with a lower risk of cataracts compared to zoledronic acid in patients with osteoporosis. These findings highlight the potential impact of osteoporosis treatment choice on ocular health. However, further studies are needed to confirm these results and establish causality.