AIMS: Recent studies have suggested an increased risk of fractures with proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs). We planned to perform a meta-analysis of fractures in patients taking PPIs and H2RAs. METHODS: We searched MEDLINE and EMBASE in September 2010 for observational studies reporting on the risk of fractures with acid-suppressing medication (PPIs and H2RA). We also checked the references lists of included studies and regulatory authority websites for additional data. We performed random effects meta-analysis of odds ratios (OR) according to fracture type and conducted subgroup analyses by duration of exposure. Heterogeneity was assessed using the I(2) statistic. RESULTS: Our review included 12 studies covering 1,521,062 patients. Pooled analysis of PPI use showed significant risk for spine fractures (4 studies, OR 1.50, 95% CI 1.32-1.72, p