Proton Pump Inhibitors Are Associated With Increased Risk of Site-Specific Nonunion After Open Reduction Internal Fixation
Abstract
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…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 410,433 participants or records.
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