Ye Carrie, Lee Kevin, Leslie William D, Lin Mu, Walker John, Kolinsky Michael
Department of Medicine, University of Alberta, Edmonton, Canada.
Department of Medicine, University of Manitoba, Winnipeg, Canada.
Osteoporos Int. 2023 Apr;34(4):735-740. doi: 10.1007/s00198-023-06690-1. Epub 2023 Feb 2.
T cell activation can lead to osteoporosis and while there are several case reports of fractures occurring after immune checkpoint inhibitor (ICI) use, to date, there are no population level studies looking at fracture risk related to ICI use.
Using Alberta Cancer Registry data, we identified all individuals treated with ICI for cancer between September 29, 2010, and March 31, 2019. Linked records from Alberta's healthcare administrative databases were assessed for the presence of fracture diagnostic codes in the year prior to and up to two years after ICI initiation. Fracture rate was stratified based on the time-period before and after ICI initiation. Fracture rates after ICI were compared to baseline.
The study cohort consisted of 1600 ICI users (mean age 65.7 years, 60% male). Most patients were treated with an anti-PD-1 agent (73.9%). ICIs were initiated on average 707.8 days after cancer diagnosis. 76 (4.8%) individuals had a remote history of a major fracture, and 141 (8.8%) had been treated with an osteoporosis medication prior to ICI treatment. The fracture rate in the year prior to ICI initiation was 11.3 per 1000 patient-years. The fracture rate in the year after ICI initiation was significantly higher at 27.3 per 1000 patient-years. The fracture rate dropped to 17.6 per 1000 patient-years in the second year after ICI initiation. The incidence rate ratio of sustaining a major fracture in the year after compared to the year prior to ICI initiation was 2.43 (95% CI 1.34-4.27).
Fracture risk may be increased in cancer patients early after initiation of ICI, and this may represent a novel immune-related adverse event.
T细胞活化可导致骨质疏松，虽然有几例免疫检查点抑制剂（ICI）使用后发生骨折的病例报告，但迄今为止，尚无针对与ICI使用相关的骨折风险的人群水平研究。
利用艾伯塔省癌症登记数据，我们确定了2010年9月29日至2019年3月31日期间所有接受ICI治疗癌症的个体。评估艾伯塔省医疗保健管理数据库中的关联记录，以确定ICI开始前一年直至开始后两年内是否存在骨折诊断代码。骨折率根据ICI开始前后的时间段进行分层。将ICI后的骨折率与基线进行比较。
研究队列包括1600名ICI使用者（平均年龄65.7岁，60%为男性）。大多数患者接受抗PD-1药物治疗（73.9%）。ICI平均在癌症诊断后707.8天开始使用。76名（4.8%）个体有既往重大骨折史，141名（8.8%）在ICI治疗前接受过骨质疏松药物治疗。ICI开始前一年的骨折率为每1000患者年11.3例。ICI开始后一年的骨折率显著更高，为每1000患者年27.3例。ICI开始后第二年的骨折率降至每1000患者年17.6例。与ICI开始前一年相比，开始后一年发生重大骨折的发病率比值为2.43（95%CI 1.34-4.27）。
ICI开始后早期癌症患者的骨折风险可能增加，这可能代表一种新的免疫相关不良事件。
