Use of proton pump inhibitors and risk of osteoporosis-related fractures

Abstract

Background: The use of proton pump inhibitors has been associated with an increased risk of hip fracture. We sought to further explore the relation between duration of exposure to proton pump inhibitors and osteoporosis-related fractures.

Methods: We used administrative claims data to identify patients with a fracture of the hip, vertebra or wrist between April 1996 and March 2004. Cases were each matched with 3 controls based on age, sex and comorbidities. We calculated adjusted odds ratios (OR) for the risk of hip fracture and all osteoporosis-related fractures for durations of proton pump inhibitor exposure ranging from 1 or more years to more than 7 years.

Results: We matched 15 792 cases of osteoporosis-related fractures with 47 289 controls. We did not detect a significant association between the overall risk of an osteoportic fracture and the use of proton pump inhibitors for durations of 6 years or less. However, exposure of 7 or more years was associated with increased risk of an osteoporosis-related fracture (adjusted OR 1.92, 95% confidence interval [CI] 1.16-3.18, p = 0.011). We also found an increased risk of hip fracture after 5 or more years of exposure (adjusted OR 1.62, 95% CI 1.02-2.58, p = 0.04), with even higher risk after 7 or more years exposure (adjusted OR 4.55, 95% CI 1.68-12.29, p = 0.002).

Interpretation: Use of proton pump inhibitors for 7 or more years is associated with a significantly increased risk of an osteoporosis-related fracture. There is an increased risk of hip fracture after 5 or more years exposure. Further study is required to determine the clinical importance of this finding and to determine the value of osteoprotective medications for patients with long-term use of proton pump inhibitors.

Figure 1: Association between continuous exposure to proton pump inhibitors and osteoporosis-related fractures (hip, vertebra or wrist). *Adjusted for income, region of residence, diagnoses (short-or long-term diabetes, epilepsy, ischemic heart disease, myocardial infarction, hypertension, arthritis, solid organ transplant, chronic obstructive pulmonary disease, substance use, depression, schizophrenia, dementia), home care use and multiple medications. The reference group was patients with no exposure to proton pump inhibitors or histamine-2-receptor antagonists. Note: CI = confidence interval.

Figure 2: Relation between continuous exposure to proton pump inhibitors and (A) hip and vertebral fractures and (B) hip fractures. *Adjusted for factors listed in Figure 1. Note: CI = confidence interval.