Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece.
Clin Endocrinol (Oxf). 2012 Dec;77(6):816-22. doi: 10.1111/j.1365-2265.2012.04459.x.
Patients treated with intravenous zoledronate frequently experience an acute phase reaction (APR) characterized by flu-like symptoms and increased levels of inflammatory cytokines. We aimed to define the role of various cytokines/adipocytokines in zoledronate-induced APR and develop a prognostic model for its prediction.
Fifty-one postmenopausal women with low bone mass were subjected to zoledronate intravenous infusion. Patients were divided into those who experienced APR (APR+) and those who did not (APR-). APR was clinically defined by body temperature and the visual analogue pain scale for musculoskeletal symptoms. White blood cell count, leucocytic subpopulations, C-reactive protein, interleukin-6, tumour necrosis factor-alpha, visfatin, resistin and leptin were measured before and 48 h following the infusion. The quantitative insulin sensitivity check index (QUICKI) and homoeostasis model of assessment - insulin resistance (HOMA-IR) were calculated to assess insulin sensitivity and resistance, respectively.
(APR+) patients were younger and had lower baseline visfatin and higher baseline lymphocytes and phosphate compared with APR- patients. QUICKI decreased and HOMA-IR increased in APR+ patients while remained unchanged in APR- patients. In binary logistic regression analysis, a model containing previous bisphosphonate treatment, age, body mass index, lymphocytes and visfatin, which predicted zoledronate-induced APR with 82·1% sensitivity and 73·9% specificity, was selected. In this model, lymphocytes (P = 0·010) and visfatin (P = 0·029) at baseline could independently predict APR.
Zoledronate-induced APR is associated with serum increases of pro-inflammatory cytokines and an increase of insulin resistance. Patients with higher lymphocytes and lower visfatin levels at baseline are at higher risk for APR.
接受唑来膦酸静脉输注的患者常出现以流感样症状和炎症细胞因子水平升高为特征的急性期反应（APR）。我们旨在确定各种细胞因子/脂肪细胞因子在唑来膦酸诱导的 APR 中的作用，并开发一种预测其的预后模型。
51 名患有低骨量的绝经后妇女接受唑来膦酸静脉输注。患者分为出现 APR（APR+）和未出现 APR（APR-）的患者。APR 是通过体温和肌肉骨骼症状的视觉模拟疼痛量表临床定义的。在输注前和输注后 48 小时测量白细胞计数、白细胞亚群、C 反应蛋白、白细胞介素-6、肿瘤坏死因子-α、内脏脂肪素、抵抗素和瘦素。计算定量胰岛素敏感检查指数（QUICKI）和稳态模型评估-胰岛素抵抗（HOMA-IR）以分别评估胰岛素敏感性和抵抗。
（APR+）患者较 APR-患者年轻，基线内脏脂肪素较低，淋巴细胞和磷酸盐较高。APR+患者的 QUICKI 降低，HOMA-IR 升高，而 APR-患者则保持不变。在二元逻辑回归分析中，选择了包含先前使用双膦酸盐治疗、年龄、体重指数、淋巴细胞和内脏脂肪素的模型，该模型以 82.1%的敏感性和 73.9%的特异性预测唑来膦酸诱导的 APR。在该模型中，基线时的淋巴细胞（P=0.010）和内脏脂肪素（P=0.029）可独立预测 APR。
唑来膦酸诱导的 APR 与血清中促炎细胞因子的增加和胰岛素抵抗的增加有关。基线时淋巴细胞较高和内脏脂肪素较低的患者发生 APR 的风险较高。
