Proton Pump Inhibitors Increase Fracture Risk, Meta-Analysis Shows

   In a meta-analysis of observational studies, proton pump inhibitors (PPIs) but not histamine2-receptor antagonists (H2RAs) modestly increased the risk of hip, spine, and any-site fractures. The research was presented at ENDO 2011: the 93rd Annual Meeting & Expo of the Endocrine Society in Boston.

   As known, there are concerns about the risk of fractures with acid-suppressive medications. Researchers from Harvard, Massachusetts General Hospital in Boston, and the University of California at San Francisco conducted a meta-analysis to evaluate any association between PPIs and H2RAs and fractures. They performed a systematic search of observational case-control or cohort studies, which primarily evaluated older adults, published from 1970 and 2010 in MEDLINE, EMBASE, and other sources. Ten publications reporting 11 studies were considered eligible for analysis.

   Following data analysis, with stratification by duration of use, the findings were similar in both men and women.  The researchers found a moderately increased summary effect estimate for risk of hip fracture among individuals taking PPIs with a risk ratio (RR) of 1.30, 95% confidence interval (CI), 1.19 to 1.43.  By contrast, H2RA use was not significantly associated with increased risk of hip fracture (RR 1.10, 95% CI, 0.94 to 1.30).  Additionally among PPI users there was an increase in spine (RR 1.56, 95% CI, 1.31 to 1.85) and any-site fractures (RR 1.16, 95% CI, 1.04 to 1.30).  The possibility of residual confounding cannot be excluded. 

   Based on these results, further skeletal evaluation should be considered in patients who are at risk for osteoporotic fracture and using PPI therapy as it confers a modestly increased risk of hip, spine, and any-site fractures.  H2RAs did not share this associated fracture risk.