Use of Proton Pump Inhibitors and Risk of Osteoporosis-Related Fractures

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Previous studies have suggested that the use of proton pump inhibitors (PPIs) for 1 or more years is associated with hip fracture and other osteoporotic fractures, but few data are available on increasing risk beyond 4 years exposure. This retrospective, matched cohort study examines the effects of long durations of PPI use on the development of osteoporosis-related fractures.

Using an administrative claims database in Manitoba, Canada, a total of 15,792 cases of osteoporosis-related vertebral fractures were matched with 47,289 controls (1:3 ratio) by age, sex, degree of co-morbidity, and ethnic background between April 1996 and March 2004. Adjusted odds ratios (OR) were calculated for the risk of hip fracture and all osteoporosis-related fractures with durations of continuous PPI exposure from 1 or more years to more than 7 years.

Use of PPIs was associated with increased risk of osteoporosis-related fracture after 7 or more years of continuous exposure (adjusted OR 1.92, 95% confidence interval [CI] 1.16–3.18, P ≤ 0.011). The risk of hip fracture was also increased after 5 or more years of exposure (adjusted OR 1.62, 95% CI 1.02–2.58, P ≤ 0.04), and there was higher risk after 7 or more years exposure (adjusted OR 4.55, 95% CI 1.68–12.29, P ≤ 0.002). No significant risk of osteoporosis-related fracture was found before 6 years or less exposure, and there was no risk of hip fracture with 4 or fewer years exposure.

These findings show that exposure of patients to PPIs for 7 or more years is associated with a significantly increased risk of osteoporosis-related fractures. PPI use for 5 years or more increases the risk of hip fracture. No risk was apparent for short-term use.

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