Proton Pump Inhibitor Use and Risk of Hip Fractures in Patients without Major Risk Factors

Abstract

To estimate the relative risk of hip fracture associated with proton pump inhibitor (PPI) use in a population without major risk factors. A two-phase, matched, nested case-control study. United Kingdom General Practice Research Database (GPRD). Phase 1 identified 4414 case patients (aged 50-79 yrs) with an incident hip fracture between 1995 and 2005 who had at least 2 years of recorded history in the GPRD; each case was matched by age, sex, and index date (date of first-time hip fracture for cases, same date for matched controls) to up to 10 controls who did not have hip fracture. Phase 2 included the 1098 case patients identified as having no major medical risk factors for hip fracture (as assessed in phase 1) and a new set of 10,923 controls without major risk factors for hip fracture matched by sex, age, index date, and duration of history in the GPRD. In phase 1, we identified major medical risk factors for hip fracture. In phase 2, we restricted the study to case patients with none of these risk factors and matched them to new controls, who also had none of the risk factors. Data on use of PPIs were collected and compared between the groups. The relative risk (RR) for hip fracture among patients who received any PPI prescription was 0.9 (95% confidence interval 0.7-1.1) compared with those with no PPI prescription. We found no evidence of an increased risk of hip fracture with increased PPI use. The RR estimates were similar in both sexes and in all age subgroups. No specific PPI was associated with an increased risk of hip fracture. Use of PPIs does not increase the risk of hip fracture in patients without major risk factors. The difference in results between our study and that of another, which indicated that PPI use increases the risk of hip fracture, may be due to residual confounding or effect modification in the latter study.