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 ( PPI s) or histamine 2 ‐receptor antagonists (H 2 RA s). 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 PPI s and H 2 RA s: 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 PPI s ( OR 1.11 [95% CI 1.01–1.22] and OR 1.31 [95% CI 1.06–1.61], respectively) and high doses of H 2 RA s ( OR 2.77, 95% CI 1.21–6.37). No duration response was observed ( OR s 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 PPI s 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.