| アブストラクト | BACKGROUND: Gabapentinoids are increasingly being prescribed in older adults (aged 60 years or older), but concerns have been raised that their adverse effects on the CNS can increase the risk of fractures. Previous studies have reported associations between gabapentinoid use and fracture, but many have not adequately addressed confounding by indication or examined risk across the treatment journey. Therefore, we aimed to investigate the temporal association between gabapentinoid treatment and fracture in older adults, and to assess whether concomitant opioid or benzodiazepine use further modifies this risk. METHODS: In this retrospective multinational population-based study, we used data from the UK Clinical Practice Research Datalink (CPRD) Aurum database and the South Korea National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS). The analysis included individuals aged 60 years or older prescribed a gabapentinoid and who had a hospitalised fracture between Jan 1, 2010, and Dec 31, 2020, in the UK and between Jan 1, 2003, and Dec 31, 2019, in South Korea. The observation period for each included individual was divided into four mutually exclusive windows: 90 days before gabapentinoid treatment (pre-exposure window), first 60 days of treatment period (focal window 1), remaining time of the treatment period (focal window 2), and all other non-treatment periods (referent window), to capture how risk varied across the treatment course. Adjusted incidence rate ratios (aIRRs) with 95% CI of fracture during different risk windows were estimated using conditional Poisson models within each country, and the country-specific aIRRs for the same risk window were then pooled using a random-effects model. FINDINGS: We included 20 030 participants in CPRD and 2935 in NHIS-HEALS in the analysis. In the CPRD cohort, 15 366 (76.7%) were women and the mean age at event was 77.85 years. In the NHIS-HEALS cohort, 2007 (68.4%) were women and the mean age at event was 69.24 years. The pooled results showed an increased risk of fracture during the pre-exposure window (aIRR 2.92, 95% CI 1.61-5.28, p=0.0004). The aIRR was 1.31 (95% CI 1.00-1.71, p=0.051) in the first 60 days of the treatment period and did not increase for the remainder of the treatment period (0.84, 0.54-1.32, p=0.45). Concurrent prescription of opioids or benzodiazepines elevated the risk of fracture, with an aIRR of 3.15 (95% CI 2.85-3.48, p<0.0001) for opioids and 1.91 (1.50-2.44, p<0.0001) for benzodiazepines during the first 60 days of gabapentinoid treatment period. INTERPRETATION: The risk of fracture was the highest in the period before the commencement of gabapentinoid treatment and declined after initiation of treatment. The results do not support a sustained causal relationship between gabapentinoid use and risk of fracture in older adults but warrant fall and fracture-prevention measures around gabapentinoid initiation. The elevated fracture risk observed with concomitant opioid or benzodiazepine use highlights the need for careful review of concurrent sedating medicines when initiating gabapentinoids. FUNDING: UK National Institute for Health and Care Research; Hong Kong Innovation and Technology Commission; Ministry of Food and Drug Safety, South Korea. |
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| 投稿者 | Yuen, Andrew S C; Chen, Boqing; Chan, Adrienne Y L; Hong, Bin; Kim, Ju Hwan; Hayes, Joseph F; Osborn, David P J; Besag, Frank M C; Howard, Robert; Wilson, Matthew G; Lau, Wallis C Y; Wong, Ian C K; Wei, Li; Shin, Ju-Young; Man, Kenneth K C |
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| 組織名 | Research Department of Practice and Policy, School of Pharmacy, University;College London, London, UK; Centre for Medicines Optimisation Research and;Education, University College London Hospitals NHS Foundation Trust, London, UK.;Aston Centre of Excellence in Pharmacotherapy Optimisation and;Pharmacoepidemiology Research, School of Pharmacy, Aston University, Birmingham,;UK; Centre for Safe Medication Practice and Research, Department of Pharmacology;and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong;Special Administrative Region, China.;School of Pharmacy, Sungkyunkwan University, Suwon, South Korea; Gerald Bronfman;Department of Oncology, Faculty of Medicine and Health Sciences, McGill;University, Montreal, Canada.;School of Pharmacy, Sungkyunkwan University, Suwon, South Korea; Department of;Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea.;Division of Psychiatry, University College London, London, UK; North London NHS;Foundation Trust, London, UK.;College London, London, UK; East London NHS Foundation Trust, Bedfordshire, UK;;Institute of Psychiatry, Psychology & Neuroscience, King's College London,;London, UK.;Division of Psychiatry, University College London, London, UK.;Department of Targeted Intervention, Division of Surgery & Interventional;Science, University College London, London, UK; Department of Anaesthesia and;Perioperative Medicine, University College London Hospitals NHS Foundation Trust,;Education, University College London Hospitals NHS Foundation Trust, London, UK;;Centre for Safe Medication Practice and Research, Department of Pharmacology and;Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong;Special Administrative Region, China; Laboratory of Data Discovery for Health;(D(2)4H), Hong Kong Science Park, Hong Kong Special Administrative Region, China.;(D(2)4H), Hong Kong Science Park, Hong Kong Special Administrative Region, China;;School of Pharmacy, Medical Sciences Division, Macau University of Science and;Technology, Macau Special Administrative Region, China; Advance Data Analytics;for Medical Science, Hong Kong Special Administrative Region, China.;Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea;;Department of Clinical Research Design & Evaluation, Samsung Advanced Institute;for Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea.;Electronic address: kenneth.man@ucl.ac.uk. |
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