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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.


Emily J Peach

Clinical Associate Professor

Jack Gibson

Andrew J Andrew J. Cooper

Li-Chia Chen

Roger D. Knaggs


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.


Peach, E. J., Pearce, F. A., Gibson, J., Andrew J. Cooper, A. J., Chen, L., & 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.

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 (OUP)
Peer Reviewed Peer Reviewed
Volume 190
Issue 7
Pages 1324-1331
Keywords opioid analgesics, bone fractures, self-controlled case series, pharmacoepidemiology
Public URL
Publisher URL
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


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