Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Opinion
  • Published:

Bisphosphonates and esophageal cancer—a pathway through the confusion

Nature Reviews Rheumatology volume 7, pages 369–372 (2011)Cite this article

Subjects

Abstract

Two recent papers that examined the association between oral bisphosphonates and the risk of esophageal cancer reported seemingly discrepant findings, despite both studies using data from the UK General Practice Research Database, from similar time periods. Each paper set out brief conclusions within their abstracts, generating two opposing impressions: that the risk of incident esophageal cancer is not significantly increased with bisphosphonate use, or that the risk is increased when bisphosphonates have been prescribed ten or more times, or for longer than 5 years. Of course, the latter conclusion was more widely reported in the popular press, and with patients arriving at the clinic wanting to discuss the reports, clinicians must be able to interpret the existing evidence correctly. In this article we discuss important methodological issues regarding the two observational studies, define areas of consensus and discrepancy, examine possible bias and confounding, and condense the results into a clinically useful summary.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Differences in study design between two analyses of data from the UK General Practice Research Database, Cardwell et al. and Green et al., in which the risks of esophageal cancer associated with bisphosphonate use were calculated.1,2

Similar content being viewed by others

References

  1. Cardwell, C. R., Abnet, C. C., Cantwell, M. M. & Murray, L. J. Exposure to oral bisphosphonates and risk of esophageal cancer. JAMA 304, 657–663 (2010).

    Article  CAS  Google Scholar 

  2. Green, J. et al. Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case–control analysis within a UK primary care cohort. BMJ 341, c4444 (2010).

    Article  Google Scholar 

  3. Watson, J., Wise, L. & Green, J. Prescribing of hormone therapy for menopause, tibolone, and bisphosphonates in women in the UK between 1991 and 2005. Eur. J. Clin. Pharmacol. 63, 843–849 (2007).

    Article  Google Scholar 

  4. Lassen, A., Hallas, J. & de Muckadell, O. B. Esophagitis: incidence and risk of esophageal adenocarcinoma—a population-based cohort study. Am. J. Gastroenterol. 101, 1193–1199 (2006).

    Article  Google Scholar 

  5. Daily Mail reporter. Drugs to fight bone thinning 'double the risk of cancer'. Daily Mail (London) (3 Sep. 2010).

  6. Askling, J. & Dixon, W. The safety of anti-tumour necrosis factor therapy in rheumatoid arthritis. Curr. Opin. Rheumatol. 20, 138–144 (2008).

    Article  CAS  Google Scholar 

  7. Meier, C. R., Schlienger, R. G., Kraenzlin, M. E., Schlegel, B. & Jick, H. HMG-CoA reductase inhibitors and the risk of fractures. JAMA 283, 3205–3210 (2000).

    Article  CAS  Google Scholar 

  8. van Staa, T. P., Wegman, S., de Vries, F., Leufkens, B. & Cooper, C. Use of statins and risk of fractures. JAMA 285, 1850–1855 (2001).

    Article  CAS  Google Scholar 

  9. de Vries, F. de Vries, C., Cooper, C., Leufkens, B. & van Staa, T. P. Reanalysis of two studies with contrasting results on the association between statin use and fracture risk: the General Practice Research Database. Int. J. Epidemiol. 35, 1301–1308 (2006).

    Article  Google Scholar 

  10. Solomon, D. H., Rekedal, L. & Cadarette, S. M. Osteoporosis treatments and adverse events. Curr. Opin. Rheumatol. 21, 363–368 (2009).

    Article  Google Scholar 

  11. Herxheimer, A. Communicating with patients about harms and risks. PLoS Med. 2, e42 (2005).

    Article  Google Scholar 

  12. Gigerenzer, G. Reckoning with risk: Learning to live with uncertainty (Penguin Books, London, 2003).

  13. Calman, K. C. & Royston, G. Risk language and dialects. BMJ 315, 939–942 (1997).

    Article  CAS  Google Scholar 

  14. Black, D. M. et al. Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur. N. Engl. J. Med. 362, 1761–1771 (2010).

    Article  CAS  Google Scholar 

  15. Gallagher, A. M., Rietbrock, S., Olson, M. & van Staa, T. P. Fracture outcomes related to persistence and compliance with oral bisphosphonates. J. Bone Miner. Res. 23, 1569–1575 (2008).

    Article  Google Scholar 

  16. Abrahamsen, B., Eiken, P. & Brixen, K. Atrial fibrillation in fracture patients treated with oral bisphosphonates. J. Intern. Med. 265, 581–592 (2009).

    Article  CAS  Google Scholar 

  17. Kim, S. Y., Kim, M. J., Cadarette, S. M. & Solomon D. H. Bisphosphonates and risk of atrial fibrillation: a meta-analysis. Arthritis Res. Ther. 12, R30 (2010).

    Article  Google Scholar 

  18. Loke Y. K., Jeevanantham V. & Singh S. Bisphosphonates and atrial fibrillation: systematic review and meta-analysis. Drug Saf. 32, 219–228 (2009).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

W. G. Dixon is supported by an MRC Clinician Scientist Fellowship (G0902272), and D. H. Solomon receives salary support from the National Institutes of Health of the USA (AR055989).

Author information

Authors and Affiliations

  1. Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK

    William G. Dixon

  2. Department of Medicine, Division of Rheumatology, Brigham & Women's Hospital, 75 Francis Street, Boston, 02115, MA, USA

    Daniel H. Solomon

Authors
  1. William G. Dixon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniel H. Solomon
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

W. G. Dixon and D. H. Solomon contributed equally to all aspects of the preparation of this manuscript.

Corresponding author

Correspondence to William G. Dixon.

Ethics declarations

Competing interests

D. H. Solomon receives a research grant from Amgen for the study of rheumatoid arthritis. W. G. Dixon declares no competing interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dixon, W., Solomon, D. Bisphosphonates and esophageal cancer—a pathway through the confusion. Nat Rev Rheumatol 7, 369–372 (2011). https://doi.org/10.1038/nrrheum.2011.60

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrrheum.2011.60

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing