The study used observational data from the Nurses' Health Study which included data for 79,899 postmenopausal women. In 2000, a questionnaire was sent to 11,080 study participants with asthma or COPD and to 11,080 randomly selected controls. This questionnaire enquired about frequency, severity and duration of heartburn and acid regurgitation. The response rate was 86%.
The resulting data set contained 565,786 person years of follow up date and included 893 cases of hip fracture. The risk of a hip fracture for users of a PPI was 2.02/1,000 person year while in non-users it was 1.51/1,000 person years. This was a 35% increase in risk (95% confidence interval 1.13 - 1.62).
After correction for factors such as body mass index, physical activity and intake of calcium the risk was similar with a hazard ratio 1.36 (95% CI 1.13 to 1.63). The authors also report that the association was not altered after correction for reasons for PPI use.
The authors note that this study contains several strengths including prospective data collection and correction for several independent risk factors for hip fracture. Disease indication for the PPI has also been reduced in this analysis. There are however some limitations also, the data are still observational, hip fracture was self-reported and not confirmed in medical records and no data were available for bone mineral density.
The authors conclude that, "chronic use of PPIs is associated with increased risk of hip fracture, particularly among women with a history of smoking". They also suggest careful evaluation of the need for long term, continuous use of PPIs, particularly among individuals with a history of smoking.
Action: This study adds to a growing body of evidence associating PPIs with fractures. Stepping down and stopping PPIs where possible would be a prudent risk management strategy.