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Background: Recent case reports suggested a link between oral bisphosphonate use and esophageal cancer. We therefore examined the association between these medications and the risk of esophageal adenocarcinoma (EAC) in patients with Barrett's esophagus (BE).Design: This was a nested, matched case-control study. Cases with incident EAC at least 6 months following BE index date were matched by incidence density sampling to controls with BE without EAC. Patients with BE were found in the national Department of Veterans Affairs computerized databases, and each filled prescriptions for oral bisphosphonates between BE diagnosis and EAC diagnosis (or corresponding dates in controls). Incidence density ratios were calculated using conditional logistic regression models.Results: In a cohort of 11,823 patients with BE, we compared 116 cases and 696 controls. Most were men (97%). Most cases and controls had at least one filled proton pump inhibitor (PPI) prescription (95 vs. 94%, P = 0.5). Filled bisphosphonate prescriptions were very uncommon (1.7 vs. 1.9%) and were not associated with EAC; the incidence density ratio was 0.92 (95% CI, 0.21-4.15).Conclusion: In patients with BE, oral bisphosphonates were not associated with an increased risk of EAC. [ABSTRACT FROM AUTHOR]