OBJECTIVE To evaluate association of first- or second-generation antipsychotic (AP) drugs with fracture risk at different levels of frailty over the age of 80 years. DESIGN Population-based cohort study. SETTING AND PARTICIPANTS United Kingdom Clinical Practice Research Datalink including 153,304 patients aged 80 years and older between 2006 and 2015. METHODS Rates of fracture and adjusted rate ratios (RR) were estimated by AP drug exposure category, adjusting for age, sex, frailty, number of deficits, and dementia diagnosis. RESULTS Data were analyzed for 165,726 treatment episodes (153,304 patients; 61.3% women; mean age 83 years; 21,365 fractures; 681,221.1 person-years of follow-up). AP exposure was associated with increasing age, frailty, and dementia diagnosis. After adjusting for frailty and covariates, first-generation AP exposure was associated with risk of any fracture, RR 1.24 (95% confidence interval 1.07-1.43, P = .003). Second-generation AP exposure was associated with femur fracture (RR 1.41, 1.22-1.64, P < .001) but less strongly with any fracture (RR 1.12, 1.01-1.24, P = .033). Fracture incidence increased with frailty level. The number of person-years of first-generation AP treatment associated with 1 additional fracture at any site was 75 (42-257) for severely frail patients but 187 (95% confidence interval 104-640) for 'fit' patients. For second-generation AP, 1 additional femur fracture might result from 173 (111-323) person-years treatment in severe frailty but 365 (234-681) person-years treatment for 'fit' patients. CONCLUSIONS AND IMPLICATIONS Frail patients are more likely to receive AP drug treatment, but their absolute risk of AP-associated fracture is substantially greater than for nonfrail patients.

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衰弱对于抗精神病药物使用与骨折风险关联的重要性：使用电子健康记录的队列研究

目的 评估第一代或第二代抗精神病 (AP) 药物与 80 岁以上不同衰弱程度的骨折风险的关联。设计 基于人群的队列研究。设置和参与者 英国临床实践研究数据链，包括 2006 年至 2015 年间 153,304 名 80 岁及以上患者。的缺陷和痴呆症的诊断。结果 分析了 165,726 次治疗的数据（153,304 名患者；61.3% 的女性；平均年龄 83 岁；21,365 次骨折；681,221.1 人年的随访）。AP 暴露与年龄增加、虚弱和痴呆诊断有关。在调整脆弱性和协变量后，第一代 AP 暴露与任何骨折风险相关，RR 1.24（95% 置信区间 1.07-1.43，P = .003）。第二代 AP 暴露与股骨骨折相关 (RR 1.41, 1.22-1.64, P < .001) 但与任何骨折相关性较低 (RR 1.12, 1.01-1.24, P = .033)。骨折发生率随着虚弱程度的增加而增加。与任何部位 1 次额外骨折相关的第一代 AP 治疗人年数对于严重虚弱的患者为 75 (42-257)，而对于“健康”患者为 187 (95% 置信区间 104-640)。对于第二代 AP，重度虚弱患者接受 173 (111-323) 人年治疗，但“健康”患者接受 365 (234-681) 人年治疗，可能会导致 1 次额外股骨骨折。结论和启示 体弱的患者更有可能接受 AP 药物治疗，