Proton pump inhibitors increase risk of bone fractures in men with cirrhosis: a population-based study

Background Bone fractures are a frequent complication in patients with cirrhosis. Proton pump inhibitors (PPIs) are among the most frequently prescribed medications and may impair bone quality and quantity. Aims To investigate whether PPI use predisposes patients with cirrhosis to bone fractures. Methods We performed a population-based case-control study exploring a sample of patients with cirrhosis derived from the Disease Analyzer database. In total, 1795 cirrhotic patients with fractures were compared to 10 235 cirrhotic patients without fractures. PPI use overall and the cumulative PPI dose 5 years prior to the index date were analyzed. To estimate the association between PPI use and fractures, logistic regression analyses were performed taking cofounding factors into consideration. Results PPI use was more frequently seen in cirrhotic patients with fractures compared to controls with cirrhosis (67.0% vs 53.4%,P < 0.001). In regression analyses, PPI use was associated with bone fractures after adjusting for important confounders (OR 1.34, 95% CI 1.20-1.51,P < 0.001). Importantly, the strongest effect of PPIs on bone fractures was seen in men and patients below 70 years of age. On further sensitivity analyses we observed a dose-dependent effect for all PPIs with the strongest effect in cirrhotic patients receiving a dose of >50 000 mg during the 5 years prior to index date (OR 1.63, 95% CI 1.32-2.03). Conclusions PPI use was associated with bone fractures in a dose-dependent fashion in patients with cirrhosis. PPI use in these patients should be based on a careful risk-benefit assessment.