Proton pump inhibitors (PPIs) are extensively used for the chronic treatment of common gastrointestinal disorders in dialysis patients. We evaluated the association between PPI use and bone fractures in hemodialysis patients in the DOPPS study.
Among 50411 (58% male) hemodialysis patients from the DOPPS dataset, 39% of patients received PPI treatment, aged 62.5±15 years, dialysis duration 588 days, BMI 25±6 Kg/m2. Bone fractures requiring hospitalization were considered. Hip fractures were analyzed as a subset. The median and the interquartile range of follow-time is 19 months (interquartile range: 9-27 months).
Overall, 6.5 (95% CI: 5.9-7.1) hip fractures every 1000 patients-years (PY) and 21 (95% CI: 20-22) bone fractures every 1000 PY were observed. On univariate logistic regression analyses, PPI use was related to an increased risk of hip (odds ratio: 2.27, 95% CI: 1.89-2.73, P<0.001) and bone fractures (odds ratio: 1.56, 95% CI: 1.41-1.72, P<0.001). In two logistic regression models (adjusting for confounding variables), a strong relationship was confirmed between PPI use with hip (odds ratio=1.68, 95% CI: 1.38-2.05, P<0.0001) and bone (odds ratio=1.34, 95% CI: 1.20-1.50, P<0.0001) fractures. Furthermore, a significant and inverse effect modification by age (P=0.03) on the relationship between PPI treatment with any bone fractures (but not with hip fractures) was found, so that the odds of bone fractures associated with PPI use was high in younger patients and progressively lower in older patients (Figure).
In hemodialysis patients, PPI use is associated with a +34% and a +68% excess risk for bone and hip fractures as compared to those untreated. Although we controlled for a series of well-known potential confounders, the possibility of residual confounding by indication cannot be excluded. The risk of bone fractures associated with PPI use was higher in younger patients.
Inverse effect modification by age on the relationship between PPI treatment with any bone fractures.
