硬骨素与OPG/RANKL在注射唑来膦酸钠治疗绝经后骨质疏松患者中浓度的早期表达  

Early expression changes of sclerostin,OPG and RANKL following zoledronic acid injection in elderly women with postmenopausal osteoporosis

作　　者：曹燕明[1] 李兴[1] 陈勇[1] 何敏辉 

机构地区：[1]广州医科大学附属第二医院骨科,510260

出　　处：《中华关节外科杂志（电子版）》2015年第2期53-57,共5页Chinese Journal of Joint Surgery(Electronic Edition)

基　　金：广东省自然科学基金(S2011010003333)

摘　　要：目的探讨在运用唑来膦酸钠治疗绝经后骨质疏松症（OP）患者中硬骨素、骨保护素（OPG）及核因子κB受体激活因子配基（RANKL）在治疗前后浓度水平变化,从而探索唑来膦酸钠的药物作用与骨转换表达的关系,为临床联合用药提供一定的实验基础。方法收集本组60~88岁诊断为绝经后OP患者22例,测定静脉注射唑来膦酸钠第0、2、7、30天患者血清中硬骨素、RANKL、OPG、CTX（Ⅰ型胶原交联羧基端肽）及PINP（Ⅰ型前胶原氨基端原肽）的浓度,并运用Pearson＇s相关性分析,分析硬骨素、RANKL、OPG与CTX、PINP的相关性。结果 （1）在注射唑来膦酸钠后,骨吸收指标CTX在第2、7、30天明显降低,并与注射前比较有统计学意义（P〈0.01）;骨形成指标PINP在第2、7、30天降低,但只在第7、30天与注射前比较有统计学意义（P〈0.01）。（2）在注射唑来膦酸钠后,硬骨素在第2、7天急剧上升并有统计学意义（P〈0.01）,在第30天后慢慢下降;硬骨素的变化与CTX的变化在第2天（r=-0.518;P〈0.05）、第7天（r=-0.571;P〈0.01）、第30天（r=-0.484;P〈0.05）呈负性相关并有统计学意义;与PINP变化在第2天（r=-0.927;P〈0.01）第7天（r=-0.562;P〈0.01）、第30天（r=-0.451;P〈0.05）呈负相关并有统计学意义。（3）在注射唑来膦酸钠后,RANKL在第2、7天上升,在第30天后下降,但无统计学意义（P〉0.05）;OPG呈上升趋势,但无统计学意义（P〉0.05）。结论由实验结果可知,在运用唑来膦酸治疗绝经后OP患者中,硬骨素的浓度早期急剧升高,而硬骨素对骨的形成起负性调节作用,因而在临床治疗中,可尝试将硬骨素单克隆抗体与唑来膦酸钠联合用药,增强患者对药物抗骨质疏松的能力,Objective To explore the variation in sclerostin,RANKL,OPG serum levels after zoledronic acid administration for postmenopausal osteoporosis in order to determine the correlation between the drug effects and the changes in bone turnover markers,and provide experimental reference for clinical medications. Methods Twenty-two postmenopausal women（ aged between 60 and 88 years）,who were admitted to the Center for the Prevention and Cure of Osteoporosis in the 2nd affiliated hospital of Guangzhou Medical University were enrolled in this study. The patients with secondary osteoporosis of other causes were previously excluded. The exclusion criteria included chronic renal or liver failure,heart failure,hypocalcemia or hypercalcemia, a prior cancer diagnosis or the patients previously received medications potentially involving bone and mineral metabolism. All the 22 women were treated with 5 mg of zoledronic acid administered intravenously in about 30 minutes at a constant speed. Before the infusion of zoledronic acid（ baseline）,then in two,seven and 30 days after the infusion,the levels of sclerostin,RANKL,OPG,c-telopeptide of typeⅠcollagen（ CTX） and Procollagen-I-N-Terminal-Propeptide（ PINP）were evaluated,and the changes of the sclerostin and RANKL,OPG were observed; the Pearson＇ s correlation analysis was carried out for the drug effects and bone resorption and formation. Results（ 1）After the zoledronic acid infusion,the CTX level decreased in day 2,day 7,and day 30 with significant difference（ P〈0. 01）; the PINP concentration decreased in day 2,day 7,and day 30,the differences between the pre-infusion data and the data in day 7 and day 30 were significant（ P〈0. 01）.（ 2） After the zoledronic acid infusion,the sclerostin level sharply increased in day 2 and day 7,and slowly declined in day 30; compared with the pre-infusion level,the difference was significant（ P〈0. 01）. The change of sclerostin showed a negative correlation with the change of CTX in day 2（ r =- 0. 518; P

关 键 词：SOST蛋白  人 RANKL蛋白 骨保护素 唑来膦酸钠 骨质疏松  绝经后 

分 类 号：R580[医药卫生—内分泌]