维生素 D 通过调节肠道对钙的吸收而对骨骼健康至关重要，而促炎细胞因子（包括 IL-1、IL-6、IL-12 和 TNF-α）已知可增加骨吸收。我们假设乳腺癌诊断时的维生素 D 和这些细胞因子可预测接受芳香酶抑制剂 (AI) 的女性的脆性骨折。在一个由 1,709 名接受 AI 治疗的乳腺癌患者组成的前瞻性队列中，我们测量了 25-羟基维生素的水平来自基线血样的 D (25OHD)、IL-1β、IL-6、IL-12 和 TNF-α。这些生物标志物与骨转换标志物（BALP 和 TRACP）、骨调节标志物（OPG 和 RANKL）、接近癌症诊断的骨矿物质密度（BMD）以及中位 7.5 年随访期间脆性骨折的风险进行了分析与维生素D缺乏的患者相比，维生素D水平充足的患者骨转换更高，骨密度更低，骨折风险更高；在控制包括 BMD 在内的协变量后，后者变得不显着，并且当排除服用维生素 D 补充剂或双磷酸盐或有骨折或骨质疏松病史的患者时，后者不再存在。 IL-1β 和 TNF-α 水平较高与骨折风险较高相关的非显着趋势（最高与最低三分位数，IL-1β：调整后 HR=1.37，95% CI=0.94-1.99；TNF- α：调整后 HR=1.38，95% CI=0.96-1.98）。我们的结果不支持促炎细胞因子或维生素 D 水平作为接受 AI 治疗乳腺癌的女性脆性骨折风险的预测因子。© 2024。作者，获得 Springer Science Business Media, LLC（Springer Nature 旗下公司）的独家许可。

Vitamin D is critical to bone health by regulating intestinal absorption of calcium, whereas proinflammatory cytokines, including IL-1, IL-6, IL-12, and TNF-α, are known to increase bone resorption. We hypothesized that vitamin D and these cytokines at the time of breast cancer diagnosis were predictive for fragility fractures in women receiving aromatase inhibitors (AIs).In a prospective cohort of 1,709 breast cancer patients treated with AIs, we measured the levels of 25-hydroxyvitamin D (25OHD), IL-1β, IL-6, IL-12, and TNF-α from baseline blood samples. The associations of these biomarkers were analyzed with bone turnover markers (BALP and TRACP), bone regulatory markers (OPG and RANKL), bone mineral density (BMD) close to cancer diagnosis, and risk of fragility fractures during a median of 7.5 years of follow up.Compared to patients with vitamin D deficiency, patients with sufficient levels had higher bone turnover, lower BMD, and higher fracture risk; the latter became non-significant after controlling for covariates including BMD and no longer existed when patients taking vitamin D supplement or bisphosphonates or with history of fracture or osteoporosis were excluded. There was a non-significant trend of higher levels of IL-1β and TNF-α associated with higher risk of fracture (highest vs. lowest tertile, IL-1β: adjusted HR=1.37, 95% CI=0.94-1.99; TNF-α: adjusted HR=1.38, 95% CI=0.96-1.98).Our results do not support proinflammatory cytokines or vitamin D levels as predictors for risk of fragility fractures in women receiving AIs for breast cancer.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.