Research

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

BMJ 2012; 344 doi: 10.1136/bmj.e372 (Published 31 January 2012)
Cite this as: BMJ 2012;344:e372
  1. Hamed Khalili, clinical and research fellow1,
  2. Edward S Huang, clinical and research fellow1,
  3. Brian C Jacobson, attending physician2,
  4. Carlos A Camargo Jr, attending physician, associate professor34,
  5. Diane Feskanich, assistant professor4,
  6. Andrew T Chan, attending physician, associate professor14
  1. 1Gastroenterology Unit, Massachusetts General Hospital, 55 Fruit Street, GRJ-728A, Boston MA 02114, USA
  2. 2Section of Gastroenterology, Boston University Medical Center, Boston MA 02118
  3. 3Department of Emergency Medicine, Massachusetts General Hospital, Boston MA 02114
  4. 4Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston MA
  1. Correspondence to: A T Chan achan{at}partners.org
  • Accepted 6 November 2011

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 (Ptrend<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 (Pinteraction=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.

Footnotes

  • An abstract of this work was presented in the Distinguished Abstract Plenary of the Clinical Practice Council at the annual meeting of the American Gastroenterological Association on 9 May 2011. The complete manuscript has not been published in any other form.

  • Contributors: HK was responsible for study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and statistical analysis. ESH was responsible for acquisition of data, analysis and interpretation of data, and critical revision of the manuscript for important intellectual content. BCJ was responsible for acquisition of data and critical revision of the manuscript for important intellectual content. CAC was responsible for acquisition of data, analysis and interpretation of data, and critical revision of the manuscript for important intellectual content. DF was responsible for acquisition of data, analysis and interpretation of data, and critical revision of the manuscript for important intellectual content. ATC was responsible for study concept and design, analysis and interpretation of data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content.

  • Funding: This study was funded by the US National Institutes of Health (grant No NIH R01 CA137178, P01 CA87969). ATC is a Damon Runyon Cancer Research Foundation clinical investigator. BCJ is supported by a grant from the National Institutes of Health (NIH R01 DK088782). HK is supported by a career development award from the IBD Working Group. ESH is supported by a career development award from the American Gastroenterological Association.

  • 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.

  • Ethical approval: The institutional review board at the Brigham and Women’s Hospital approved this study.

  • Data sharing: Requests for access to data, statistical code, questionnaires, and technical processes may be made by contacting the corresponding author at achan@partners.org

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

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