首次使用唑来膦酸的急性期反应预测及对肝肾功能影响的分析

Prediction of the acute phase response of the first use of zoledronic acid and analysis its effect on hepatorenal function

目的观察首次使用唑来膦酸的急性期反应(Acute Phase Response,APR)对血细胞计数及对肝肾功能指标变化的影响,以分析常规实验室检查是否存在APR的预测因子及评估临床用药的安全性。方法对2013年1月-2014年6月于我院首次使用唑来膦酸治疗的66例绝经后老年女性骨质疏松症患者进行回顾性研究,按是否出现APR分为反应组和无反应组。记录发生APR情况,注射前后行血液分析、生化等实验室检查,记录相关数据,统计分析使用前后数据是否存在差异,并对相关因素行多因素回归分析,试图找出APR预测因子,对比肝肾功能指标,评估用药安全性。结果 66例骨质疏松症患者出现APR共42人,APR发生率为63.6%,其中最常见为发热34例(51.5%),骨关节肌肉疼痛18例(27.2%),四肢乏力12例(18.1%),呕吐5例(7.5%),头痛4例(6.0%)。注射后反应组中心粒细胞(P=0.009)、嗜酸性粒细胞(P=0.005)、碱性磷酸酶(P=0.005)较无反应组显著升高,淋巴细胞(P=0.002)及单核细胞(P=0.042)显著降低。肝肾功能指标中仅碱性磷酸酶(P=0.005)显著升高。多因素回归分析显示,较小年龄及单核细胞基线水平较高的患者更容易出现APR。结论注射唑来膦酸后APR发生率较高,但多为一过性反应,程度较轻,注射前后预防和干预能有效缓解,注射后对肝肾功能无明显影响,用药安全性较高。较小年龄及更高基线值的单核细胞与APR显著相关,但二者目前不能作为APR的准确预测因子。

Objective To observe the acute phase response（ APR） after the first use of zoledronic acid and its effect on whole blood cell count and the parameters of hepatorenal function before and after the use,and to analysis if the clinical and laboratory parameters can predict zoledronic acid-induced APR and the safety of the drug. Methods Sixty-six postmenopausal elderly women with osteoporosis,who were treated with intravenous zoledronic acid for the first time in our hospital from January 2013 to June2014,were retrospectively studied. They were divided into APR group（ APR ＋） and no APR group（ APR-） according to their response after the infusion. The APR situation was recorded. Blood analysis,laboratory parameters,and related data before and after the injection were recorded. Data were compared and analyzed to look for the predictive factors. The hepatorenal function was compared and evaluated for the drug safety. Re sults Forty-three patients experienced APR（ 63. 6%）. Among those,34 had fever（ 51. 5%）,18 had musculoskeletal pain（ 27. 2%）,12 had limb weakness（ 18. 1%）,5 had vomiting（ 7. 5%）,and 4 had headache（ 6. 0%）. Compare to those in the APR-group,the neutrophils,eosinophilic granulocytes,and alkaline phosphatase increased significantly in the APR ＋ group,but the lymphocytes and monocytes decreased significantly. Multifactor regression analysis showed that the patients with younger age and high level of baseline monocytes were highly correlated with APR.Conclusion The incidence of APR induced by the first use of zoledronic acid is high. Intravenous zoledronic acid is quite safe for the liver and kidney function. Our data suggest that pretreatment higher monocyte number and younger age increases the risk of APR,but both of them can not be the predictive factor of APR.