Risperidone and aripiprazole, commonly used antipsychotics in children with autism spectrum disorder (ASD), have previously been associated with elevated fracture risk in other populations. The aim of this study was to evaluate and compare the risk of fracture among children with ASD using risperidone or aripiprazole. This was a retrospective, propensity-score matched cohort study, set between January 2013 and December 2018. We used the MarketScan Medicaid insurance data, which covers multiple states of the United States. We included ASD children aged 2–18 years, who were new users of aripiprazole or risperidone and with no prior history of antipsychotic use or fractures. The main exposure was the continued use of aripiprazole or risperidone. The incidence rates of any fracture during follow-up were evaluated, and the risk between aripiprazole and risperidone was compared via Cox-proportional hazard models. Results were stratified by age, sex, duration of exposure and fracture site. In total, 3312 patients (78% male; mean [SD] age 11.0 [3.7] years) were identified for each cohort. Over the full duration of follow-up, fracture incidence rates per 1000 patient-years were 23.2 for risperidone and 38.4 for aripiprazole (hazard ratio and 95% confidence interval: 0.60 [0.44–0.83]). Risks were similar between cohorts throughout the first 180 days on treatment, but significantly higher in the aripiprazole group thereafter. Extremity fractures drove most of the increased risk, with the biggest differences in lower leg and ankle fractures. Differences widened for children aged 10 years or younger (HR [95% CI]: 0.47 [0.30–0.74]). In conclusion, compared to aripiprazole, risperidone was associated with 40% lower risk of fracture. Further analysis on the mechanism and long-term bone health of antipsychotic-treated children with ASD is warranted.

中文翻译：

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利培酮与阿立哌唑在自闭症谱系障碍儿童和青少年中的骨折风险

利培酮和阿立哌唑是自闭症谱系障碍 (ASD) 儿童常用的抗精神病药，以前曾与其他人群的骨折风险升高有关。本研究的目的是评估和比较使用利培酮或阿立哌唑的 ASD 儿童的骨折风险。这是一项在 2013 年 1 月至 2018 年 12 月之间进行的回顾性、倾向评分匹配的队列研究。我们使用了 MarketScan 医疗补助保险数据，该数据涵盖美国多个州。我们纳入了 2-18 岁的 ASD 儿童，他们是阿立哌唑或利培酮的新使用者，之前没有抗精神病药使用史或骨折史。主要暴露是继续使用阿立哌唑或利培酮。评估随访期间任何骨折的发生率，并通过 Cox 比例风险模型比较了阿立哌唑和利培酮之间的风险。结果按年龄、性别、暴露时间和骨折部位分层。总共有 3312 名患者（78% 为男性；平均 [SD ] 年龄 11.0 [3.7] 岁）被确定为每个队列。在整个随访期间，利培酮每 1000 患者年的骨折发生率为 23.2，阿立哌唑为 38.4（风险比和 95% 置信区间：0.60 [0.44–0.83]）。在治疗的前 180 天内，队列之间的风险相似，但此后阿立哌唑组的风险显着更高。四肢骨折是导致风险增加的主要原因，小腿和脚踝骨折的差异最大。10 岁或以下儿童的差异扩大（HR [95% CI]：0.47 [0.30–0.74]）。总之，与阿立哌唑相比，利培酮的骨折风险降低了 40%。有必要对接受抗精神病药物治疗的 ASD 儿童的机制和长期骨骼健康进行进一步分析。