OBJECTIVES: To investigate the association between proton pump inhibitor (PPI) use and fracture nonunion risk across different anatomical fracture locations and patient age groups. METHODS: Design : Retrospective cohort study utilizing propensity score matching to control for confounding variables. Setting: Multicenter database analysis (TriNetX). Patient Selection Criteria: This study included patients who underwent operative fixation of a fracture of the humerus, radius/ulna, femur, or tibia/fibula corresponding to OTA/AO fracture types 11-13, 21-23, 31-33, and 41-43, respectively. Fractures that occurred between 2015 and 2023 were identified using ICD and CPT codes. Propensity matching balanced cohorts by age, sex, race/ethnicity, comorbidities (e.g., obesity, chronic kidney disease, hypertension), bone health conditions (osteoporosis, osteopenia), and medication use affecting fracture healing (NSAIDs, Denosumab, Alendronate, Vitamin D). Outcome Measures and Comparisons: The primary outcome was rate of fracture nonunion. Comparisons included anatomical fracture site (humerus, radius/ulna, femur, tibia/fibula), and patient age groups (18-44, 45-64, ≥65 years). RESULTS: 410,433 patients were analyzed, with balanced cohorts of PPI users and non-users. PPI use significantly increased nonunion risk in tibia/fibula (4.44% vs 2.21%; HR: 2.08, 95% CI: 1.86-2.31, p <0.0001) and radius/ulna fractures (3.36% vs. 1.88%; HR: 1.85, 95% CI: 1.56-2.20, p <0.0001). The highest vulnerability was among younger patients (ages 18-44) with tibia/fibula fractures (HR: 10.87, 95% CI: 6.95-16.99). Nonunion rates were higher, though not statistically significant for femur (4.34% vs. 3.88%; HR: 1.11, 95% CI: 0.97-1.27, p =0.0958) and humerus fractures (6.06% vs. 5.21%; HR: 1.21, 95% CI: 1.01-1.44, p =0.0802). CONCLUSIONS: Proton pump inhibitor (PPI) use was associated with increased nonunion risk, particularly in tibia/fibula and radius/ulna fractures. Younger patients demonstrated greater susceptibility to PPI-associated nonunion. The findings indicated that PPI exposure may have adversely affected fracture healing in specific anatomical or demographic subgroups and warranted further investigation. LEVEL OF EVIDENCE: Level III.
Romoff et al. (Tue,) studied this question.