Opioids and the risk of fracture: a self-controlled case series study in the Clinical Practice Research Datalink

Peach, Emily J; Pearce, Fiona A; Gibson, Jack; Andrew J. Cooper, Andrew J; Chen, Li-Chia; Knaggs, Roger D.

Abstract

Self-controlled study designs can be used to assess the association between exposures and acute outcomes while controlling for important confounders. Using routinely collected health data, a self-controlled case series design was used to investigate the association between opioid use and bone fractures in 2008–2017 among adults registered in the United Kingdom Clinical Practice Research Datalink. The relative incidence of fracture was estimated, comparing periods when exposed and unexposed to opioids, adjusted for time-varying confounders. Of 539,369 people prescribed opioids, 67,622 sustained fractures and were included. The risk of fracture was significantly increased when exposed to opioids, with an adjusted incidence rate ratio of 3.93 (95% confidence interval: 3.82, 4.04). Fracture-risk was greatest in the first week of starting opioids (adjusted incidence rate ratio: 7.81, 95% confidence interval: 7.40, 8.25) and declined with increasing duration of use. Re-starting opioids after a gap in exposure significantly increased fracture-risk (adjusted incidence rate ratio: 5.05, 95% confidence interval: 4.83, 5.29) when compared to non-use. These findings highlight the importance of raising awareness of fractures among patients at opioid initiation and demonstrate the utility of self-controlled methods for pharmacoepidemiologic research.

Citation

Peach, E. J., Pearce, F. A., Gibson, J., Andrew J. Cooper, A. J., Chen, L.-C., & Knaggs, R. D. (2021). Opioids and the risk of fracture: a self-controlled case series study in the Clinical Practice Research Datalink. American Journal of Epidemiology, 190(7), 1324-1331. https://doi.org/10.1093/aje/kwab042

• Journal Article Type: Article
• Acceptance Date: Dec 14, 2020
• Online Publication Date: Feb 19, 2021
• Publication Date: 2021-07
• Deposit Date: Dec 15, 2020
• Publicly Available Date: Feb 20, 2022
• Journal: American Journal of Epidemiology
• Print ISSN: 0002-9262
• Publisher: Oxford University Press
• Peer Reviewed: Peer Reviewed
• Volume: 190
• Issue: 7
• Pages: 1324-1331
• DOI: https://doi.org/10.1093/aje/kwab042
• Keywords: opioid analgesics, bone fractures, self-controlled case series, pharmacoepidemiology
• Public URL: https://nottingham-repository.worktribe.com/output/5149219
• Publisher URL: https://academic.oup.com/aje/advance-article/doi/10.1093/aje/kwab042/6144851
• Additional Information: This is a pre-copyedited, author-produced version of an article accepted for publication in American Journal of Epidemiology; following peer review. Emily J Peach, Fiona A Pearce, Jack Gibson, Andrew J Cooper, Li-Chia Chen, Roger D Knaggs, Opioids and the Risk of Fracture: A Self-Controlled Case Series Study in the Clinical Practice Research Datalink, American Journal of Epidemiology, Volume 190, Issue 7, July 2021, Pages 1324–1331 is available online at https://doi.org/10.1093/aje/kwab042.