Proton-pump Inhibitor Use and Fracture Risk: An Updated Systematic Review and Meta-analysis.

BACKGROUND

This study's objective was to evaluate the association between proton-pump inhibitor (PPI) use and bone fracture incidence and bone mineral density (BMD) by meta-analyzing the estimates reported by epidemiological and cohort studies.

METHODS

Data were acquired from studies identified after a literature search in electronic databases. Odds ratios (ORs), hazard ratios (HRs), and risk ratios (RRs) between PPI use and bone fracture incidence were pooled under the random effects model, and meta-analysis of standardized mean differences between PPI users and controls in cross-sectional values and BMD changes was conducted.

RESULTS

Thirty-three studies fulfilled the eligibility criteria. These studies provided data from 2,714,502 individuals with a mean age of 66.91 years (95% confidence interval [CI], 63.37-70.46); 33.21% (95% CI, 30.44-35.99) were males and 64.61% (95% CI, 60.73-68.49) were females. Overall, fracture incidence was 22.04% (95% CI, 16.10-27.97) in PPI users and 15.57% (95% CI, 12.28-18.86) in controls. The overall effect size of the point estimate was 1.28 (95% CI, 1.22-1.35) between PPI use and bone fracture incidence. There was a trend towards increased fracture incidence from short duration use: OR 1.29 (95% CI, 1.19-1.40), medium duration use: OR 1.33 (95% CI, 1.12-1.55) and long duration use: OR 1.62 (95% CI, 1.33-1.90). There was no significant difference in the standardized mean differences between PPI users and controls, either in cross-sectional BMD values or in the BMD change observed in longitudinal studies.

CONCLUSIONS

Pooling of ORs, HRs, and RRs suggested that PPI use might increase fracture risk. However, there was no effect of PPI use on BMD.