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Published on: November 8, 2024
Proton Pump Inhibitors Are Associated With Increased Risk of Site-Specific Nonunion After Open Reduction Internal
Melissa Romoff1, Michael S Kim, Courtney Spitzer
1Department of Orthopaedic Surgery, University of California, Irvine, School of Medicine, Orange, CA.
Objectives:
To investigate the association between proton pump inhibitor (PPI) use and fracture nonunion risk across different anatomical fracture locations and patient age groups.
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 (eg, 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:
A total of 410,433 patients were analyzed, with balanced cohorts of PPI users and nonusers. PPI use significantly increased nonunion risk in tibia/fibula [4.44% vs. 2.21%; hazard ratio (HR), 2.08, 95% confidence interval (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, although 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:
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:
Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
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