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

Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study

Hamed Khalili  1 , Edward S Huang, Brian C Jacobson, Carlos A Camargo Jr, Diane Feskanich, Andrew T Chan
Affiliations

Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: a prospective cohort study

Hamed Khalili et al. BMJ. .

Abstract

Objective: To examine the association between chronic use of proton pump inhibitors (PPIs) and risk of hip fracture.

Design: Prospective cohort study.

Setting: Nurses' Health Study, which originally recruited from the 11 most populous states in the US.

Participants: 79,899 postmenopausal women enrolled in the Nurses' Health Study who provided data on the use of PPIs and other risk factors biennially since 2000 and were followed up to 1 June 2008.

Main outcome measure: Incident hip fracture

Results: During 565,786 person years of follow-up, we documented 893 incident hip fractures. The absolute risk of hip fracture among regular users of PPIs was 2.02 events per 1000 person years, compared with 1.51 events per 1000 person years among non-users. Compared with non-users, the risk of hip fracture among women who regularly used PPIs for at least two years was 35% higher (age adjusted hazard ratio 1.35 (95% confidence interval 1.13 to 1.62)), with longer use associated with increasing risk (P(trend)<0.01). Adjustment for risk factors, including body mass index, physical activity, and intake of calcium did not materially alter this association (hazard ratio 1.36 (1.13 to 1.63)). These associations were also not changed after accounting for reasons for PPI use. The relation between PPI use and fracture differed by smoking history (P(interaction)=0.03). Among current and former smokers, PPI use was associated with greater than 50% increase in risk of fracture, with a multivariate hazard ratio for fracture of 1.51 (1.20 to 1.91). In contrast, among women who never smoked there was no association (multivariate hazard ratio 1.06 (0.77 to 1.46)). In a meta-analysis of these results with 10 prior studies, the pooled odds ratio of hip fracture associated with PPI use was 1.30 (1.25 to 1.36).

Conclusion: Chronic use of PPIs is associated with increased risk of hip fracture, particularly among women with a history of smoking.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

None
Results of meta-analysis of our results with 10 published studies of risk of hip fracture with chronic use of a proton pump inhibitor (PPI). For the study by Yu et al, risk estimates were only provided for men and women separately
See this image and copyright information in PMC

Comment in

References

    1. Targownik LE, Metge C, Roos L, Leung S. The prevalence of and the clinical and demographic characteristics associated with high-intensity proton pump inhibitor use. Am J Gastroenterol 2007;102:942-50. - PubMed
    1. Wolfe MM, Soll AH. The physiology of gastric acid secretion. N Engl J Med 1988;319:1707-15. - PubMed
    1. Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA 2006;296:2947-53. - PubMed
    1. Bliuc D, Nguyen ND, Milch VE, Nguyen TV, Eisman JA, Center JR. Mortality risk associated with low-trauma osteoporotic fracture and subsequent fracture in men and women. JAMA 2009;301:513-21. - PubMed
    1. Brauer CA, Coca-Perraillon M, Cutler DM, Rosen AB. Incidence and mortality of hip fractures in the United States. JAMA 2009;302:1573-9. - PMC - PubMed

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