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Pharmacoepidemiol Drug Saf. 2018 Jun;27(6):596-603. doi: 10.1002/pds.4406. Epub 2018 Feb 28.

Proton pump inhibitor use and the risk of fractures among an older adult cohort.

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Department of Epidemiology, University of Washington, Seattle, WA, USA.
Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
Division of General Internal Medicine, Department of Medicine, University of Washington, Seattle, WA, USA.



The purpose of the study is to determine if the use of a proton pump inhibitor (PPI) is associated with an increased fracture risk, as some prior studies have suggested.


This retrospective cohort study included data on 4438 participants aged 65 and older who had no fracture in the year prior to baseline and had ≥5 years of enrollment history in Kaiser Permanente Washington, an integrated healthcare delivery system in Seattle, WA, during 1994 to 2014. Time-varying cumulative exposure to PPIs was determined from automated pharmacy data by summing standard daily doses (SDDs) across fills, and patients were categorized as no use (reference group, ≤30 SDD), light use (31-540 SDD), moderate use (541-1080 SDD), and heavy use (≥1081 SDD). Incident fractures were assessed using International Classification of Diseases, Ninth Revision codes from electronic medical records. Potential confounders, chosen a priori, were assessed at baseline and at each 2-year follow-up visit. Fracture risk was analyzed using a Cox proportional hazards model.


Over a mean follow-up of 6.1 years, 802 (18.1%) participants experienced a fracture. No overall association was found between PPI use and fracture risk. Adjusted hazard ratios comparing users to the referent category were 1.08 (95% CI 0.83-1.40) for light users, 1.31 (95% CI 0.86-1.95) for moderate users, and 0.95 (95% CI 0.68-1.34) for heavy users. Among patients with SSD > 30, no appreciable increase in fracture risk was present in persons with recent versus distant use (adjusted hazard ratio of 1.14 [95% CI 0.91-1.42]).


No association was observed between PPI use and fracture risk among older adults.


comorbidity; fracture; medications; older adult; pharmacoepidemiology; proton pump inhibitor

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