Use of proton-pump inhibitor (PPI) therapy is associated with an increased risk of fragility fractures, data from a large, prospective cohort study reveal.

PPI therapy is commonly used to manage stomach acid-related diseases. An association of PPI therapy and increased fracture risk has been reported in a number of retrospective studies; however, in many of these studies adjustment was only made for a limited number of risk factors for fracture. In addition, the magnitude of the fracture risk associated with use of PPIs was unclear, as various levels of increased fracture risk have been reported in different studies.

Fraser and co-workers studied a cohort of 9,423 Canadian community-dwelling men and women over a period of 10 years to examine the association of PPI use and fragility fractures. Incident fractures were confirmed by medical or radiographic reports. At study start, 261 individuals (2.8%) were receiving PPI therapy, but the number had increased to 530 (6.9%) after 5 years and to 675 (12.1%) after 10 years. Over the 10-year period, 1,295 individuals had one or more fragility fracture.

PPI use was associated with an increased risk of fractures at any site (HR 1.40, 95% CI 1.11–1.77), after adjustment for a number of fracture risk factors, including BMD. Additional adjustment for use of bisphosphonates or restriction of the outcome to hip fractures gave similar results.

The researchers conclude that their findings support the growing body of literature on the increased risk of fragility fractures associated with use of PPIs, and they highlight the importance of this association, despite its modest strength, owing to the widespread use of PPIs and the considerable morbidity and mortality associated with fragility fractures.