The Impact of Proton Pump Inhibitors on Pseudarthrosis Rates Following Multi-Level Lumbar Fusion.

Background: Multi-level lumbar fusion carries exceptionally high pseudarthrosis risk, with reported rates reaching 35% in contemporary series; however, the impact of proton pump inhibitors (PPIs) on fusion outcomes remains underexplored in this high-risk population. Recent evidence associates PPIs with increased pseudarthrosis in single-level cervical and lumbar fusions, given their established links to impaired bone metabolism. This study is the first to evaluate their association, specifically in multi-level lumbar fusion, where extended fusion constructs and heightened biomechanical demands amplify biological vulnerability to pseudarthrosis. Methods: This retrospective cohort study analyzed 9,608 adults undergoing elective ≥2-level posterior lumbar interbody fusion/transforaminal lumbar interbody fusion from the TriNetX database. The exposed cohort comprised patients with sustained postoperative PPI use (≥3 months), while controls had no PPI prescriptions. Rigorous 1:1 propensity score matching (PSM) balanced 15 covariates, including demographics (age, sex, race), comorbidities (diabetes, osteoporosis, gastroesophageal reflux disease), body mass index categories, and medication exposures (nonsteroidal anti-inflammatory drugs) between cohorts. Pseudarthrosis incidence was assessed at standardized 6-month, 1-year, and 3-year postoperative intervals. Statistical significance was defined as p<0.05. Results: After PSM (n=2,739 per cohort), PPI users did not demonstrate a significantly elevated pseudarthrosis risk at 6 months (17.9% vs. 16.2%; risk ratio [RR]=1.10, p=0.136). However, significant risk increases emerged at 1 year (20.3% vs. 16.5%; RR=1.23, p<0.001) and 3 years (22.0% vs. 18.9%; RR=1.16, p<0.01), revealing a time-dependent effect. Conclusions: This large-scale analysis demonstrated that postoperative PPI use is significantly associated with increased long-term pseudarthrosis risk following multi-level lumbar fusion, with absolute risk elevations of 3.8% (1 year) and 3.1% (3 years), a notable finding given baseline nonunion rates reported to exceeding 35% in multilevel constructs. PPIs may thus represent a modifiable perioperative risk factor, and careful evaluation of prolonged PPI therapy is warranted to minimize the risk of compromised fusion. Optimizing perioperative PPI management may offer surgeons a tangible opportunity to improve spinal fusion outcomes.