The relationship among proton pump inhibitors, bone disease and fracture

There is growing concern about a possible association between the use of proton pump inhibitors (PPIs) and the development of fragility fractures, most notably hip and vertebral fractures. As PPIs are widely used in clinical practice, this association is of paramount clinical importance.

The authors review the published papers analyzing the relationship between PPI use and the occurrence of fragility fractures. The authors also explore the data supporting possible mechanisms through which PPIs may increase the risk of fracture, including the effects of PPIs on calcium homeostasis, bone mineral density and direct effects of PPIs on bone metabolism.

Overall, though multiple observational studies have demonstrated an association between PPIs and fragility fractures, the lack of a proven mechanism through which PPIs increase the risk of fracture suggests that this association may not be causal. At this time, the authors do not recommend discontinuing PPIs in patients with a history of fracture or those at increased risk of fracture. However, clinicians should still endeavor to avoid using PPIs in situations where benefits are minimal or clinical indications are lacking.