Association between proton pump inhibitor use and risk of fracture: A population-based case-control study.

Objectives: The purpose of this study was to reconfirm the association between the risk of fracture and proton pump inhibitor use and to establish evidence for defining a high-risk group of patients among proton pump inhibitor users.

Methods: A nested case-control study was performed using data from the National Health Insurance Sharing Service database from the period January 2007 to December 2017. The study population included elderly women aged ≥65 years with claims for peptic ulcer or gastro-esophageal reflux disease. The cases were all incidental osteoporotic fractures, and up to two controls were matched to each case by age, osteoporosis, and Charlson comorbidity index. Conditional logistic regression was used to calculate the adjusted odds ratio and 95% confidence interval (CI).

Results: A total of 21,754 cases were identified, and 43,508 controls were matched to the cases. The adjusted odds ratio of osteoporotic fractures related to the use of proton pump inhibitors was 1.15 (95% CI: 1.11-1.20). There was a statistically significant interaction between proton pump inhibitor and bisphosphonate use (p<0.01). The risk of fracture in patients using proton pump inhibitors was 1.15 (95% CI: 1.08-1.92) in bisphosphonate users and 1.11 (95% CI: 1.03-1.20) in bisphosphonate non-users.

Conclusion: Concomitant use of bisphosphonates and proton pump inhibitors will likely increase the risk of osteoporotic fractures in women aged 65 and over, and caution should be exercised in this high-risk group of patients.