PPI use not associated with hip fractures in postmenopausal women; modest association found for other fractures, study reveals

Among postmenopausal women, proton pump inhibitor (PPI) use does not appear to be associated with hip fractures, new data indicate, although use of these agents is modestly associated with clinical spine, forearm or wrist, and total fractures. Researchers conducted a prospective analysis of 161,806 postmenopausal women aged 50 to 79 years. The participants had no history of hip fracture and had been enrolled in the Women's Health Initiative observational study and clinical trials. The...

Among postmenopausal women, proton pump inhibitor (PPI) use does not appear to be associated with hip fractures, new data indicate, although use of these agents is modestly associated with clinical spine, forearm or wrist, and total fractures.

Researchers conducted a prospective analysis of 161,806 postmenopausal women aged 50 to 79 years. The participants had no history of hip fracture and had been enrolled in the Women's Health Initiative observational study and clinical trials. The investigators obtained data regarding the patients' medication use during in-person interviews at baseline and at 3 years. Complete information was available for 130,487 women. Mean follow-up was 7.8 years.

The study's primary outcome measure was self-reported fractures (hip, clinical spine, forearm or wrist, and total fractures). In a subsample of nearly 7,000 patients, the primary outcome measure also included 3-year change in bone mineral density (BMD).

The annualized rate of hip fractures was 0.15% for nonusers and 0.19% for PPI users. Data from the fully adjusted models indicated that PPI use was not related to an increased risk of hip fracture (HR, 1.00; 95% CI, 0.71-1.40) but was related to a significantly increased risk of clinical spine, forearm or wrist, and total fractures. Specifically, the women who used PPIs had a 47% increased risk of clinical spine fracture (HR, 1.47; 95% CI, 1.18-1.82), a 26% increased risk of forearm or wrist fractures (HR, 1.26; 95% CI, 1.05-1.51), and a 25% increased risk for total fractures (HR, 1.25; 95% CI, 1.15-1.36).

There was no difference in BMD measurements between the PPI users and nonusers at baseline. The 3-year change in BMD at the hip marginally favored no PPI use, although no difference was noted for BMD change at other sites between the PPI users and nonusers.

"Questions remain regarding the potential risk associated with long-term PPI use and fracture risk; thus, based on the accumulation of evidence, it is prudent for clinicians to periodically reevaluate the need for long-term PPI therapy," the authors concluded. "For those older adults who do require long-term PPI therapy, it is reasonable to focus on using the lowest effective dose, ensuring adequate dietary calcium intake, and adding calcium supplements when necessary." (Gray SL, et al. Arch Intern Med 2010;170:765-771.)