Article Text
PDF
Abstract
Introduction Bisphosphonates are becoming a common treatment for osteoporosis particularly after discovery of the association between hormone replacement therapy and increased risk of breast cancer. As osteoporosis develops with age, treatment is a long-term intervention. Randomised control trials typically have limited follow-up times, which restricts investigation of the effects of the drugs on risk of primary cancers. A few observational studies have demonstrated a reduced risk of breast cancer and possibly of endometrial cancer in bisphosphonate users. Two epidemiological studies have studied the effect of the drugs on oesophageal cancer but did not reach any definite conclusions. So far, no effects on colorectal and stomach cancer have been shown. This study will investigate the association of bisphosphonates with risks of the 10 most common primary cancers.
Methods and analysis A series of nested case–control studies will be based on the general population using records from 660 UK general practices within the QResearch Database. Cases will be patients with primary cancers diagnosed between 1996 and 2011. Each case will be matched by age, sex, practice and calendar year to five controls, who are alive and registered with the practice at the time of diagnosis of the case. Exposure to bisphosphonates will be defined as at least one prescription during the study period. For the most common cancers with substantial numbers of observations, the effect of the duration of the treatment and different types of bisphosphonates will be studied. Conditional logistic regression will be applied to produce ORs adjusted for smoking status, socioeconomic status, ethnicity, cancer-specific co-morbidities and use of other medications.
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.
Statistics from Altmetric.com
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Files in this Data Supplement:
- Data Supplement - Manuscript file of format pdf
Footnotes
To cite: Vinogradova Y, Coupland C, Hippisley-Cox J. Exposure to bisphosphonates and risk of cancer: a protocol for nested case–control studies using the QResearch Primary care database. BMJ Open 2012;2:e000548. doi:10.1136/bmjopen-2011-000548
Funding This work has been funded by the Division of Primary Care of University of Nottingham. Apart from that, this research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare no support from any additional organisation for the submitted work. JH-C is professor of clinical epidemiology at the University of Nottingham and unpaid director of QResearch, a not-for-profit organisation, which is a joint partnership between the University of Nottingham and Egton Medical Information System (commercial IT supplier for 60% of general practices in the UK). JH-C is also a paid director of ClinRisk Limited, 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. CC is associate professor of medical statistics at the University of Nottingham and a paid consultant statistician for ClinRisk Limited; no other relationships or activities that could appear to have influenced the submitted work.
Ethics approval This protocol has been independently peer-reviewed by the QResearch Scientific Board and has been reported to Trent Research Ethics Committee in accordance with the agreed procedure. A full report containing the study findings will be prepared and a paper based on the report will be submitted to a peer-reviewed journal.
Contributors JH-C had the original idea for this study. CC contributed to the development of the idea. YV reviewed the literature, contributed to the study design and wrote the draft of the manuscript. JH-C and CC critically reviewed the paper. YV is the guarantor of the study. All authors approved the submitted version.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement It will be possible to access the data after the publication of the results but only on premises of the University of Nottingham. The full protocol and statistical code will be available from the authors after the publication of the results.