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Exposure to bisphosphonates and risk of gastrointestinal cancers: series of nested case-control studies with QResearch and CPRD data

BMJ 2013; 346 doi: (Published 16 January 2013) Cite this as: BMJ 2013;346:f114
  1. Yana Vinogradova, research fellow in medical statistics,
  2. Carol Coupland, associate professor and reader in medical statistics,
  3. Julia Hippisley-Cox, professor of clinical epidemiology and general practice
  1. 1Division of Primary Care, University Park, Nottingham NG2 7RD, UK
  1. Correspondence to: Y Vinogradova yana.vinogradova{at}
  • Accepted 18 December 2012


Objective To investigate the association between use of bisphosphonates estimated from prescription information and risk of gastrointestinal cancers.

Design Series of nested case-control studies.

Setting General practices in the United Kingdom contributing to the QResearch primary care database (660) and the Clinical Practice Research Datalink (CPRD) (643).

Participants Patients aged ≥50 with a diagnosis of a primary gastrointestinal cancer in 1997-2011, each matched with up to five controls by age, sex, practice, and calendar year.

Main outcome measures Odds ratios for incident gastrointestinal cancers (colorectal, oesophageal, gastric) and use of bisphosphonates, adjusted for smoking status, ethnicity, comorbidities, and use of other drugs.

Results 20 106 and 19 035 cases of colorectal cancer cases, 5364 and 5135 cases of oesophageal cancer cases, and 3155 and 3157 cases of gastric cancer were identified from QResearch and CPRD, respectively. Overall bisphosphonate use (at least one prescription) was not associated with risk of colorectal, oesophageal, or gastric cancers in either database. Adjusted odds ratios (95% confidence interval) for QResearch and CPRD were 0.97 (0.79 to 1.18) and 1.18 (0.97 to 1.43) for oesophageal cancer; 1.12 (0.87 to 1.44) and 0.79 (0.62 to 1.01) for gastric cancer; and 1.03 (0.94 to 1.14) and 1.10 (1.00 to 1.22) for colorectal cancer. Additional analyses showed no difference between types of bisphosphonate for risk of oesophageal and colorectal cancers. For gastric cancer, alendronate use was associated with an increased risk (1.47, 1.11 to 1.95; P=0.008), but only in data from the QResearch database and without any association with duration and with no definitive confirmation from sensitivity analysis.

Conclusions In this series of population based case-control studies in two large primary care databases, exposure to bisphosphonates was not associated with an increased risk of common gastrointestinal cancers.


  • We acknowledge the contribution of EMIS and the University of Nottingham for expertise in creating and maintaining QResearch, and to the EMIS practices that contribute data, without whom this research would not be possible.

  • Contributors: JH-C had the original idea for this study. CC contributed to the development of the idea and the study design. YV reviewed the literature, contributed to the study design, undertook the primary analysis and the first interpretation, and wrote the first draft of the paper. JH-C and CC critically reviewed the paper. All authors approved the submitted version. YV is guarantor.

  • Funding: This work was funded by the division of primary care of University of Nottingham.

  • Competing interests: All authors have completed the Unified Competing Interest form at (available on request from the corresponding author) and declare no support from any additional organisation for the submitted work. JH-C is an unpaid director of QResearch, a not-for-profit organisation that is a joint partnership between the University of Nottingham and EMIS (commercial IT supplier for 60% of general practices in the UK). JH-C is also a paid director of ClinRisk, which produces open and closed source software to ensure the reliable and updatable implementation of clinical risk algorithms within clinical computer systems to help improve patient care.

  • Ethical approval: This protocol has been published in BMJ Open. It has also independently peer reviewed by the QResearch Scientific Board and has been reported to Trent research ethics committee in accordance with the agreed procedure (reference No MREC/03/4/021). For CPRD data analysis, the protocol was approved by independent scientific advisory committee (reference No ISAC 11_149).

  • Data sharing: Descriptive statistics for users and non-users of bisphosphonates and results of unadjusted and sensitivity analyses are available from the corresponding author.

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: and

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