Ocular adverse effects of bisphosphonates and association with osteonecrosis from a real-world database

While bisphosphonates are widely used to treat osteoporosis, ocular adverse effects (OAEs) and their associations with serious systemic side effects, such as osteonecrosis, remain unexplored in large, diverse cohorts.

Retrospective cohort study from a deidentified aggregated multinational electronic health records database. Patients were included based on no prior recorded history of OAEs, recorded prescription of bisphosphonates and a subsequent visit. The risk of osteonecrosis for patients with and without OAEs after bisphosphonate initiation was assessed. Propensity score matching was used to control for demographic factors and prior autoimmune conditions. Rates of OAEs were compared between patients on intravenous or oral bisphosphonates.

A cohort of 944,559 patients was identified. The cohort mean age was 75 years. The most common OAEs were dry eyes (1.73%), cornea and ocular surface inflammation (0.97%), and uveitis (0.17%). Patients with any OAEs with bisphosphonate use compared to those without OAEs had an increased risk of osteonecrosis (RR: 1.48, (1.30, 1.93)), with the highest increased risk for zoledronate (RR: 2.22, (1.63-3.03)). Furthermore, intravenous bisphosphonates compared to oral bisphosphonates had an increased risk of dry eyes (RR: 1.27 (1.20, 1.36)) at all timepoints.

Although rarer than reported in literature, our large cohort size revealed that patients on bisphosphonates with OAEs had an increased risk of osteonecrosis compared to those without OAEs. Patients on intravenous compared to oral bisphosphonates were at increased risk for OAEs. These findings guide ophthalmologists to identify OAEs from bisphosphonate use and to be vigilant for increased risks of systemic side effects.