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

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


Purpose: 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.

Methods: 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.

Results: 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]).

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

Keywords: comorbidity; fracture; medications; older adult; pharmacoepidemiology; proton pump inhibitor.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Dose-Response Relationship, Drug
  • Female
  • Follow-Up Studies
  • Fractures, Bone / chemically induced
  • Fractures, Bone / epidemiology*
  • Gastroesophageal Reflux / drug therapy
  • Humans
  • Incidence
  • Male
  • Peptic Ulcer / drug therapy
  • Prospective Studies
  • Proton Pump Inhibitors / administration & dosage
  • Proton Pump Inhibitors / adverse effects*
  • Retrospective Studies
  • Risk Factors
  • Washington / epidemiology


  • Proton Pump Inhibitors