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02-02-2012 | Gastroenterology | Article

PPI use raises hip fracture risk in smokers


Free abstract

MedWire News: Older women who use proton pump inhibitors (PPIs) for heartburn or gastroesophageal reflux have a significantly increased risk for hip fracture, with research showing that current or former smokers are at particular risk.

"In view of the steadily growing prevalence of regular PPI use, our estimates of an absolute increase in risk of five hip fractures per 10,000 person-years associated with PPI use suggest the potential for a high burden of fractures attributable to PPIs across the population," write Andrew Chan (Massachusetts General Hospital, Boston, USA) and co-authors in the BMJ.

"These findings further support the recent decision of the Food and Drug Administration to revise labeling of PPIs to incorporate concerns about a possible increase in risk of fractures with these drugs."

The team examined data from the Nurses' Health Study for 79,899 postmenopausal women. The women were asked at 2-year intervals between 1994 and 2006 if they had regularly used PPIs in the past 2 years.

In all, 893 hip fractures were reported over 565,786 person-years of follow-up.

Analysis revealed that the absolute risk for hip fracture was significantly higher among women who had regularly used PPIs than those who had not (2.02 vs 1.51 events per 1000 person-years).

After adjusting for age, the hazard ratio (HR) for hip fracture among women who had used PPIs for at least 2 years was a significant 1.35, with risk increasing with duration of use.

Although the risk did not significantly alter after adjustment for body mass index, physical activity, and calcium intake (HR=1.36), there was a significant relationship between smoking history and hip fracture risk, Chan et al report.

Specifically, the HR for hip fracture for use of PPIs in current and former smokers was 1.51, whereas for never smokers, there was no significant increased risk for hip fracture with PPI use.

Reassuringly, the increased risk for hip fracture fell 2 years after women discontinued PPI use, and did not significantly differ from nonusers after this point.

"Smoking and PPIs may have a synergistic effect on fracture risk mediated by impaired calcium absorption," Chan et al write. "In addition, experimental studies have postulated that both PPIs and smoking influence osteoclast function, perhaps suggesting a shared negative effect on bone remodeling."

They conclude that further research should be conducted into the joint impact of smoking and PPI use.

By Lynda Williams

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