The effect of proton pump inhibitors on fracture risk: report from the Canadian Multicenter Osteoporosis Study

Abstract

A large Canadian cohort was studied over 10 years to see if proton pump inhibitor (PPI) use increased the risk of sustaining a fragility fracture. We found an increased risk of fracture in individuals who used PPIs. The risk remained after controlling for other known fracture risk factors.

Introduction: Multiple retrospective studies have linked proton pump inhibitor use with increased risk of fragility fracture. We prospectively studied the association between PPI use and fracture in a large cohort over a 10-year period while controlling for known fracture risk factors.

Methods: We studied 9,423 participants in the Canadian Multicenter Osteoporosis Study. The cohort was formed in 1995-1997 and followed for 10 years with monitoring for incident nontraumatic fracture and PPI use. Cox regression analyses were used to assess the association between PPI use and incident fracture risk.

Results: PPI use, coded as a time-dependent variable, was associated with a shorter time to first nontraumatic fracture, hazard ratio (HR)=1.75 (95% confidence interval (CI) 1.41-2.17, p<0.001). After controlling for multiple risk factors, including femoral neck bone density, the association remained significant, HR=1.40 (95% CI 1.11-1.77, p=0.004). Similar results were obtained after controlling for bisphosphonate use, using PPI "ever" use, or when the outcome was restricted to hip fracture.

Conclusions: In this large prospective population-based cohort study, we found an association between PPI use and increased risk of fragility fracture. Although the increased risk found was modest, this finding is important, given the high prevalence of PPI use and the excess morbidity and mortality associated with osteoporosis-related fractures.

Conflict of interest statement

LAF has been on the speaker’s bureau for Amgen. WDL has received speaker fees and unrestricted research grants from Merck Frosst; unrestricted research grants from Sanofi-Aventis, Warner Chilcott, Novartis, Amgen, and Genzyme and from advisory boards for Genzyme, Novartis, and Amgen. LET, advisory boards and grants for investigator initiated research from Astra Zeneca Canada and Janssen Canada. AP has been a consultant/speaker for Amgen, Aventis, Eli Lilly, Merck Frosst, Novartis, Procter & Gamble, Servier, and Wyeth-Ayerst; conducted clinical trials for Eli Lilly, Merck Frosst, Novartis, Procter & Gamble, and Sanofi-Aventis; and received unrestricted grants from Amgen, Eli Lilly, Merck Frosst, Procter & Gamble, and Sanofi-Aventis. JDA has received research support and has been a consultant of Amgen, Astra Zeneca, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Nycomed, Pfizer, Procter & Gamble, Roche, Sanofi-Aventis, Servier, Warner Chilcott, and Wyeth.

Figures

Fig. 1

Kaplan–Meier curve showing unadjusted fragility fracture-free survival by PPI use (defined as PPI ever use). PPI= proton pump inhibitor. P-value from the log rank test

Fig. 2

Kaplan–Meier curve showing unadjusted hip fracture-free survival by PPI use (defined as PPI ever use). PPI= proton pump inhibitor. P-value from the log rank test