Association of benzodiazepine and opioid use with hip fracture treated with arthroplasty: a nationwide case-control study

Yepes-Calderón, M.; Nelissen, R.G.H.H.; Bouvy, M.L.; Steenbergen, L.N. van; Dahan, A.; Rosendaal, F.R.; Gademan, M.G.J. (2026)

Article / Letter to editor

Background: Despite safety warnings, the use of benzodiazepines and opioids is increasing among community-dwelling older adults. We investigated whether these medications, individually and in combination, are associated with an increased risk of hip fracture treated with arthroplasty (HF-arthroplasty) and assessed their population-level impact.

Methods: In this nationwide case-control study, we linked the Dutch Arthroplasty Register and the Dutch Foundation for Pharmaceutical Statistics. The resulting cohort does not include patients residing in or discharged to institutional care. Cases were all HF-arthroplasties in patients >= 65-years between 2013 and 2022. Estimates for controls were obtained from the general Dutch population in the same sex and 5-year age group during the calendar month of indexation. Medication use was defined as >= 1 dispensation of benzodiazepines, opioids, or both in the month before surgery (cases) or the corresponding calendar month (controls). We calculated stratified odds ratios (ORs) using the Mantel-Haenszel method, as well as the population attributable fraction (PAF).

Results: We included 15,728 HF-arthroplasties (43% men; mean age 80 +/- 8 years) and approximate to 3,228,768 monthly controls (range 25,848-528,914 per stratum). Among cases, 8.2% used benzodiazepines, 8.3% opioids, and 2.5% both medications in the pre-procedure month, compared to 5.9%, 2.6%, and 0.9% monthly use rates among controls, respectively. Benzodiazepine use was associated with HF-arthroplasties in individuals between 65-69-years with e.g. an OR of 1.75 [95%-CI 1.25-2.44] for males. Opioid use was associated with a higher risk of outcome across all groups, with ORs between 1.88 [95%-CI 1.43-2.46] and 5.08 [95%-CI 3.89-6.63]. The individual risk of HF-arthroplasty was highest with concurrent use, especially in individuals aged 65-69 years with ORs between 5.23 [95%-CI 3.73-7.33] and 7.51 [95%-CI 4.92-11.48]. At the population level, opioid exposure had the greatest impact, with the proportion of patients with hip fractures treated with arthroplasty potentially attributable to opioid use ranging from 3.7% to 6.0%.

Conclusions: Benzodiazepine and opioid use are associated with an increased risk of HF-arthroplasty, particularly among individuals aged 65-69 years and when used concurrently. Opioid use contributed the most to the population burden, underscoring the importance of responsible opioid use in older adults, especially in combination with benzodiazepines.

• Benzodiazepine
• Opioids
• Concurrent use
• Hip fracture
• Pharmacoepidemiology

• All authors: Yepes-Calderón, M.; Nelissen, R.G.H.H.; Bouvy, M.L.; Steenbergen, L.N. van; Dahan, A.; Rosendaal, F.R.; Gademan, M.G.J.
• Date: 2026-02-11
• Journal: BMC Geriatrics
• Volume: 26
• Issue: 1
• DOI: doi:10.1186/s12877-025-06803-x