Proton-pump inhibitors and risk of fractures: an update meta-analysis

Osteoporos Int. 2016 Jan;27(1):339-47. doi: 10.1007/s00198-015-3365-x.


To identify the relationship between proton-pump inhibitors (PPIs) and the risk of fracture, we conducted an update meta-analysis of observational studies. Results showed that PPI use was associated with a modestly increased risk of hip, spine, and any-site fracture.

Introduction: Many studies have investigated the association of proton-pump inhibitors (PPIs) with fracture risk, but the results have been inconsistent. To evaluate this question, we performed a meta-analysis of relevant observational studies.

Methods: A systematic literature search up to February 2015 was performed in PubMed. We combined relative risks (RRs) for fractures using random-effects models and conducted subgroup and stratified analyses.

Results: Eighteen studies involving a total of 244,109 fracture cases were included in this meta-analysis. Pooled analysis showed that PPI use could moderately increase the risk of hip fracture [RR = 1.26, 95 % confidence intervals (CIs) 1.16–1.36]. There was statistically significant heterogeneity among studies (p < 0.001; I 2 = 71.9 %). After limiting to cohort studies, there was also a moderate increase in hip fracture risk without evidence of study heterogeneity. Pooling revealed that short-term use (<1 year) and longer use (>1 year) were similarly associated with increased risk of hip fracture. Furthermore, a moderately increased risk of spine (RR = 1.58, 95 % CI 1.38–1.82) and any-site fracture (RR = 1.33, 95 % CI 1.15–1.54) was also found among PPI users.

Conclusion: In this update meta-analysis of observational studies, PPI use modestly increased the risk of hip, spine, and any-site fracture, but no evidence of duration effect in subgroup analysis.

Publication types

  • Meta-Analysis

MeSH terms

  • Hip Fractures / chemically induced
  • Humans
  • Observational Studies as Topic
  • Osteoporotic Fractures / chemically induced*
  • Proton Pump Inhibitors / adverse effects*
  • Risk Assessment / methods
  • Spinal Fractures / chemically induced


  • Proton Pump Inhibitors