Study of the Association Between Hip Fracture and Acid-suppressive Drug Use in a UK Primary Care Setting

Objectives: We aimed to clarify the nature of the association between hip fracture risk and use of proton pump inhibitors (PPIs) or histamine2 -receptor antagonists (H2 RAs).

Methods: We identified patients 40-89 years of age with a recorded hip fracture diagnosis in 2000-2008 using The Health Improvement Network, a UK primary care research database. Computerized records were reviewed and questionnaires sent to primary care physicians to validate hip fracture cases. A cohort study with a nested case-control analysis was performed to estimate the association between the use of acid-suppressive drugs and hip fracture.

Results: Overall incidence of hip fracture per 1000 person-years was 1.31 (95% confidence interval [CI] 1.28-1.33). There was a modest increased risk of hip fracture after adjustment for potential confounders (odds ratios [OR] during current use of PPIs and H2 RAs: 1.09 [95% CI 1.01-1.17] and 1.04 [95% CI 0.90-1.19], respectively). Relative to nonuse, an increased risk of fracture was observed with medium and high doses of PPIs (OR 1.11 [95% CI 1.01-1.22] and OR 1.31 [95% CI 1.06-1.61], respectively) and high doses of H2 RAs (OR 2.77, 95% CI 1.21-6.37). No duration response was observed (ORs for current PPI use less than 1 month and 5 years or longer: 1.16 [95% CI 0.94-1.43] and 1.02 [95% CI 0.87-1.20], respectively).

Conclusions: Patients treated with PPIs showed a modest increased risk of hip fracture after adjustment for potential cofounders. Any remaining association between PPI use and hip fracture risk may be attributable to residual confounding.