Peptic ulcer disease and risk of hip fracture: a general population-based cohort study

Previous studies reported proton pump inhibitors (PPIs) use may increase the risk of fracture; however, the findings may be susceptible to indication bias since peptic ulcer disease (PUD), one major indication for PPIs, may affect skeletal health. Determining whether PUD would increase hip fracture risk may help identify high risk population and explore risk factors. We conducted a cohort study using data from The Health Improvement Network (THIN) in the UK. THIN contains patient information such as disease diagnosis and medicine prescriptions. Up to five non-PUD individuals (n=138,265) were matched to each case of incident PUD (n=27,653) by age, sex, and body mass index. We examined the association between PUD and hip fracture by a multivariable Cox-proportional hazard model. We repeated the same analysis among individuals with incident PUD and gastroesophageal reflux disease (GERD) (n=27,160), another disease with similar indication for PPIs, as a positive control exposure. Over a mean of 5.6 years follow-up, hip fracture occurred in 589 individuals with PUD and 2,015 individuals without PUD (3.8 vs 2.6/1000 person-years), with a multivariable-adjusted hazard ratio (HR) being 1.44 (95%CI: 1.31 to 1.58). The association persisted among subgroups stratified by sex and age. In positive control exposure analysis, the hip fracture risk was also higher in PUD than GERD (3.8 vs 2.4/1000 person-years; multivariable-adjusted HR=1.65, 95%CI: 1.45 to 1.7). This general population-based cohort study suggests, after controlling for acid-lowering medication and other potential risk factors, PUD is independently associated with an increased risk of hip fracture.