Proton Pump Inhibitors and Histamine-2 Receptor Antagonists in Spinal Fusion: A Systematic Review

Study DesignSystematic Review.ObjectivesTo evaluate the impact of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2 blockers) on spinal fusion outcomes.MethodsA systematic search of PubMed (MEDLINE) was conducted for studies published between January 2000 and July 2025 using Title/Abstract terms for PPIs, H2 blockers, spine, and fusion. Eligible studies were English-language articles assessing the relationship between acid suppression and spinal fusion outcomes. Two reviewers independently screened studies and extracted data.ResultsOf 798 records screened, five studies met inclusion criteria: three retrospective cohort studies, one animal study, and one prospective study evaluating H2 blocker use. Four of the five studies evaluated PPIs. All three clinical studies observed higher pseudarthrosis rates among postoperative PPI users undergoing spinal fusion. The animal model found no significant fusion impairment. The H2 blocker study showed reduced inflammatory markers but did not assess osseous union.ConclusionsCurrent evidence suggests an association between PPI use and impaired spinal fusion, particularly in the cervical and lumbar spine. In contrast, H2 blockers appear to have a more neutral skeletal profile, though no studies have directly evaluated their impact on spinal fusion or pseudarthrosis rates. Most available data on PPIs are derived from retrospective studies or animal models, with substantial heterogeneity in surgical level, fusion construct, PPI type, and follow-up duration. Future research should prioritize prospective, randomized studies or large registry-based analyses to clarify the causal relationship between acid suppression therapy and spinal fusion.