Proton-Pump Inhibitor Use Is Associated with Increased Risk of Nonunion Following Tibiotalar Fusion, Subtalar Fusion, and Triple Arthrodesis.

Abstract

Tibiotalar, subtalar, and triple arthrodesis are surgical interventions for end-stage joint disease affecting the ankle joint or joints of the hindfoot. Failure to achieve union of the fused joint is a feared complication and is associated with significant morbidity. Proton pump inhibitors (PPIs) may impair bone remodeling through suppression of osteoclast activity. To evaluate the association between PPI use and risk of nonunion following tibiotalar, subtalar, and triple arthrodesis STUDY DESIGN: Retrospective cohort study using the The TriNetX US Collaborative Network. Patients 18 years or older who underwent tibiotalar, subtalar, or triple arthrodesis from 2006 to 2026 were included and categorized based on perioperative PPI exposure. The PPI and non-PPI cohorts were propensity score matched by age, sex, comorbidities, and medication use. Measure of association and survival analyses were performed on the matched cohorts to determine differences in risk of nonunion. This study included 9,744 patients who underwent tibiotalar or hindfoot arthrodesis. Across all exposure windows, PPI use was associated with significantly increased risk of nonunion following tibiotalar arthrodesis. Nonunion occurred in 20.3% of PPI users compared with 12.8% of non-PPI users (RR 1.588; 95% CI, 1.443 - 1.749; p < 0.001). Time-to-event analysis demonstrated increased risk among PPI users (HR 1.587; 95% CI, 1.429 - 1.762; log-rank p < 0.001). Perioperative use of PPIs was associated with significantly higher risk of nonunion following tibiotalar, subtalar, and triple arthrodesis. Orthopedic surgeons should weigh the benefits of PPI use against the potential risk of nonunion, especially in patients with risk factors for compromised arthrodesis.