TOPLINE

The overall risk for adverse ocular effects from bisphosphonate therapy appears to be low, with events including dry eyes, cornea and ocular surface inflammation, and, rarely, uveitis. Patients who received intravenous bisphosphonates had a higher risk for ocular events than those who received oral therapy, and experiencing an ocular adverse effect was associated with an increased risk for osteonecrosis.

METHODOLOGY:

• Researchers analyzed de-identified electronic health records from the TriNetX Global Collaborative Network to identify ocular adverse events related to the use of bisphosphonates and their associations with serious systemic problems.
• They included 944,559 patients (mean age, 75 years; 81.1% women) who received a bisphosphonate (alendronate, zoledronate, ibandronate, pamidronate, or risedronate), had no prior eye disease, and were followed up for at least 1 year after the first prescription.
• The occurrence of ocular adverse events was assessed at multiple timepoints after the initiation of bisphosphonates: 1 month, 3 months, 6 months, 1 year, 2 years, 3 years, and 5 years.
• Events were identified using standard diagnostic codes and classified as cornea and ocular surface inflammation, uveitis, and dry eyes.
• A secondary analysis using propensity score matching compared the rates of osteonecrosis at 1, 3, and 5 years between bisphosphonate users with and without adverse ocular effects.

TAKEAWAY:

• The most prevalent adverse effect was dry eyes, with the incidence increasing progressively from 0.26% at 1 month to 4.52% at 5 years; over the same interval, the incidence of cornea and ocular surface inflammation rose from 0.13% to 2.81% and that of uveitis increased from 0.04% to 0.39%.
• After propensity score matching, patients who experienced adverse effects had a higher risk for osteonecrosis than those who did not experience them at 1 year (relative risk [RR], 1.6), 3 years (RR, 1.7), and 5 years (RR, 1.8; P < .0001 for all); uveitis, ocular surface inflammation, and dry eyes each were associated with an increased risk for osteonecrosis at 5 years.
• Among the bisphosphonates studied, zoledronate showed the highest risk for osteonecrosis at 1 year (RR, 2.224; 95% CI, 1.6-3.0).
• Intravenous bisphosphonates demonstrated a consistently higher risk for dry eyes than oral administration across all timepoints, with RRs of 1.35 at 1 month, 1.20 at 3 months, 1.27 at 6 months, and 1.13 at 1 year (P < .0001 for all).

IN PRACTICE:

“Though the overall risk of ocular side effects was low, the proportion of patients with adverse effects continued to increase with continued bisphosphonate treatment,” the researchers reported.

SOURCE:

The study was led by Samuel H. Kim, of the Medical Scientist Training Program at Stanford University School of Medicine in Stanford, California. It was published online on December 26, 2025, in Eye.

LIMITATIONS:

The study relied on standard diagnosis codes and prescription data for classification, which may have led to patient misclassification or exclusion. Patients receiving ocular care outside the TriNetX system could have been missed in the analysis. The study could not evaluate the effects of discontinuing bisphosphonate therapy or characterize the longitudinal course of adverse effects. 

DISCLOSURES:

The study received support from the E. Matilda Ziegler Foundation for the Blind and Research to Prevent Blindness, Inc. One author reported receiving grant support from the National Eye Institute. Another author disclosed serving in consulting/advisory roles and conducting research for multiple pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.