Proton pump inhibitor use and bone fractures in patients with chronic kidney disease

Background: Patients with chronic kidney disease (CKD) are at high risk for bone fractures, which are associated with high morbidity and mortality. Proton pump inhibitors (PPI) have been linked to an increased risk for fractures in the general population as well as in patients with need for hemodialysis, but studies in patients with CKD are currently missing.

Methods: We performed a population-based observational case-control study exploring a sample of patients with CKD derived from the IQVIATM Disease Analyzer database. Patients with and without fractures were matched using the 1:1 nearest neighbor propensity score matching method. To investigate the association between PPI use and fractures, multivariable logistic regression analyses were performed adjusting for confounding factors.

Results: In total, 6076 patients with and 6076 patients without fractures were matched and subsequently available for analyses. In the total cohort, PPI use was associated with an increased risk for fractures [odds ratio (OR) 1.68; 95% confidence interval (95% CI) 1.55-1.83]. This association was noted for nearly all types of fractures. The strongest association between PPI use and fractures was found in patients below the age of 60 years with a PPI prescription for longer than 2 years (OR 6.85; 95% CI 1.85-25.38). The same was true when analyzing cumulative PPI doses. Here, patients below the age of 60 years with a cumulative PPI dose above 16 000 mg (highest quartile) had the highest risk for fractures (OR 4.62; 95% CI 1.87-11.44). There was no difference between men or women regarding the association between PPI use and fractures.

Conclusions: This study provides evidence that PPI use is associated with fractures in patients with CKD. Deprescription of PPI in patients without an indication for treatment could be a modifiable risk factor to reduce fracture risk in this high-risk group.