Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov 4;7(11):e2444488.
doi: 10.1001/jamanetworkopen.2024.44488.

Gabapentinoids and Risk of Hip Fracture

Miriam T Y Leung  1 , Justin P Turner  1   2   3   4 , Clara Marquina  1 , Jenni Ilomäki  1   5 , Tim Tran  6 , Katsiaryna Bykov  7 , J Simon Bell  1   5   8
Affiliations

Gabapentinoids and Risk of Hip Fracture

Miriam T Y Leung et al. JAMA Netw Open. .

Abstract

Importance: The increased use of gabapentinoids has been most pronounced in older people who are also susceptible to hip fractures.

Objective: To investigate the overall association between gabapentinoids and the risk of hip fractures and the stratified association across age groups, frailty status, and history of chronic kidney disease.

Design, setting, and participants: This was a case-case-time-control study in patients hospitalized for hip fracture in Victoria, Australia, between March 1, 2013, and June 30, 2018, with at least 1 prescription for a gabapentinoid before fracture. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% CI for gabapentinoid dispensing in the index (1-60 days prefracture) compared with the reference (121-180 days prefracture) period. To adjust for the underlying time trend in gabapentinoid use, each index case was matched with up to 5 controls, selected from future cases of the same age and sex. Subgroup analyses were conducted in subgroups with or without chronic kidney disease (CKD), frailty scores less than 5, and frailty scores 5 and above. Frailty was computed using the Hospital Frailty Risk Score (HFRS). Data were analyzed from November 2023 to April 2024.

Exposure: Gabapentinoids (pregabalin or gabapentin).

Main outcome and measure: Hip fracture.

Results: Of 28 293 patients hospitalized for hip fractures, 2946 (1752 [59.5%] aged ≥80 years; 2099 [71.2%] female) were dispensed a gabapentinoid before hip fracture. Gabapentinoid dispensing was associated with increased odds of hip fractures (OR, 1.96; 95% CI, 1.66-2.32). After adjusting for the exposure-time trend and concomitant use of other central nervous system medications, the odds of hip fractures remained elevated (OR, 1.30; 95% CI, 1.07-1.57). The association between gabapentinoid dispensing and hip fracture was higher in patients with HFRS 5 and above (OR, 1.75; 95% CI, 1.31-2.33) and CKD (OR, 2.41; 95% CI, 1.65-3.52).

Conclusions and relevance: In this case-case-time-control study of Australian residents hospitalized for hip fracture, gabapentinoid use was associated with an increased risk of hip fractures, especially in patients who were frail or had chronic kidney disease. In addition to the known risk associated with kidney impairment, frailty status may be an important risk factor when considering use of gabapentinoids.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Ms Leung reported receiving a research training scholarship from the Australian Government outside the submitted work. Dr Ilomäki reported receiving grants from Amgen, National Health and Medical Research Council, Dementia Australia Research Foundation, Yulgilbar Foundation, National Breast Cancer Foundation, Medical Research Future Fund, AstraZeneca, and the Australian Government outside the submitted work. Dr Bykov reported receiving grants from National Institutes of Health and the Agency for Healthcare Research and Quality during the conduct of the study. Dr Bell reported receiving grants from the Dementia Australia Research Foundation during the conduct of the study; grants from the GlaxoSmithKline Supported Studies Programme, Amgen, Dementia Centre for Research Collaboration, National Health and Medical Research Council, Medical Research Future Fund, the Victorian Government Department of Health and Human Services, the Australian Government Department of Health and Aged Care, Yulgilbar Foundation, Aged Care Quality and Safety Commission, Dementia Centre for Research Collaboration, Pharmaceutical Society of Australia, and Society of Hospital Pharmacists of Australia; and consulting fees from the Pharmaceutical Society of Australia and the Society of Hospital Pharmacists of Australia outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Schematic Representation of Case-Case-Time-Control Study Design
aThe exclusion window was 5 years to 1 day before the index date. The comorbidities assessment window was 5 years before the index date to the baseline assessment window (day 0). The frailty assessment window was 2 years to 1 day before the index date. bIndex and reference periods were the exposure assessment periods for gabapentinoids and time-varying covariates (ie antidepressants, antipsychotics, benzodiazepines, and opioids).
Figure 2.
Figure 2.. Study Flow Diagram
See this image and copyright information in PMC

References

    1. Chan AYL, Yuen ASC, Tsai DHT, et al. . Gabapentinoid consumption in 65 countries and regions from 2008 to 2018: a longitudinal trend study. Nat Commun. 2023;14(1):5005. doi:10.1038/s41467-023-40637-8 - DOI - PMC - PubMed
    1. Johansen ME, Maust DT. Update to gabapentinoid use in the United States, 2002-2021. Ann Fam Med. 2024;22(1):45-49. doi:10.1370/afm.3052 - DOI - PMC - PubMed
    1. Ashworth J, Bajpai R, Muller S, et al. . Trends in gabapentinoid prescribing in UK primary care using the Clinical Practice Research Datalink: an observational study. Lancet Reg Health Eur. 2023;27:100579. doi:10.1016/j.lanepe.2022.100579 - DOI - PMC - PubMed
    1. Schaffer AL, Busingye D, Chidwick K, Brett J, Blogg S. Pregabalin prescribing patterns in Australian general practice, 2012-2018: a cross-sectional study. BJGP Open. 2021;5(1):bjgpopen20X101120. doi:10.3399/bjgpopen20X101120 - DOI - PMC - PubMed
    1. IQVIA Institute for Human Data Science . Medicine use and spending in the U.S.—a review of 2018 and outlook to 2023. 2019. Accessed October 9. 2024. https://www.iqvia.com/insights/the-iqvia-institute/reports-and-publicati...

Publication types