NMA: Nonprescription Medicines Academy

Regular Use of Proton Pump Inhibitors Increases Hip Fracture Risk by 35%

April 4th, 2012

In an evaluation of data from the Nurses’ Health Study, chronic use of proton pump inhibitors (PPIs) by postmenopausal women was associated with an increased risk of hip fracture, with the strongest risk observed in women with the longest duration of use or a history of smoking.

The prospective cohort study included information from 79,899 postmenopausal women who responded to questions about PPI use and other risk factors biennially beginning in 2000. The authors analyzed data collected through June 1, 2008.

A total of 893 incident hip fractures were documented during 565,786 person years of follow-up. The absolute risk of hip fracture among regular PPI users was 2.02 events per 1,000 person years, compared with 1.51 events per 1,000 person years among non-users. The risk of hip fracture was 35% higher among women who used PPIs regularly for at least 2 years than among non-users (age-adjusted hazard ratio, 1.35; 95% CI, 1.13–1.62). Longer duration of PPI use was associated with increasing risk (P <0.01). Adjustment for risk factors associated with PPI use and risk of hip fracture—including body mass index, physical activity, and intake of calcium—did not materially alter this association (hazard ratio, 1.36; 95% CI, 1.13–1.63). Among current and former smokers, PPI use was associated with a greater than 50% increase in the risk of fracture (multivariate hazard ratio for fracture, 1.51; 95% CI, 1.20–1.91). No association was seen among women who never smoked (multivariate hazard ratio, 1.06; 95% CI, 0.77–1.46).

The authors also conducted a meta-analysis of these results added to the results of 10 previous studies. The pooled odds ratio of hip fracture associated with PPI use was 1.30 (95% CI, 1.25–1.36).

BMJ. 2012 Jan 30;344:e372. doi: 10.1136/bmj.e372.