金天格胶囊治疗原发性骨质疏松症的有效性及安全性:随机、双盲双模拟、阳性药平行对照、多中心临床试验  

Efficacy and safety of Jintiange capsule in the treatment of primary osteoporosis:a randomized,double⁃blind,double⁃dummy,positive⁃controlled,multicenter clinical trial

作　　者：王鸥 夏维波 成志峰[2] 夏培金[3] 王亮[4] 沈洁[5] 孔西建 曾玉红[7] 晁爱军[8] 闫莉梅 林华[10] 孙海飚[11] 程群 朱梅[13] 胡侦明[14] 章振林[15] 唐海[16] 尚美霞 WANG Ou;XIA Wei-bo;CHENG Zhi-feng;XIA Pei-jin;WANG Liang;SHEN Jie;KONG Xi-jian;ZENG Yu-hong;CHAO Ai-jun;YAN Li-mei;LIN Hua;SUN Hai-biao;CHENG Qun;ZHU Mei;HU Zhen-ming;ZHANG Zhen-lin;TANG Hai;SHANG Mei-xia(Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Endocrinology of National Heath Commission, Beijing 100730, China;Department of Endocrinology, the Fourth Affiliated Hospital of Harbin Medical University, Haerbin 150001, China;Department of Endocrinology, the Central Hospital of Fuling District, Chongqing 408099, China;Department of Geriatric Medicine, the Eighth Medical Center of Chinese PLA General Hospital, Beijing 100091, China;Department of Endocrinology and Metabolism, the Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China;Osteoporosis Medical Center, Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital), Luoyang 471002, Henan, China;Department of Osteoporosis, Honghui Hospital of Xi'an Jiaotong University Medical School, Xi'an 710086, China;Department of Osteoporosis, Tianjin Hospital of Tianjin City, Tianjin 300299, China;Department of Endocrinology, Changchun Central Hospital, Changchun 130041, China;Department of Orthopedic, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China;Department of Orthopedic, First Hospital of Shanxi Medical University, Taiyuan 030001, China;Department of Osteoporosis, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China;Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin 300052, China;Department of Orthopedic, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China;Department of Osteoporosis and Bone Diseases, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200233, China;Department of Orthopedic, Beijing

机构地区：[1]中国医学科学院北京协和医学院北京协和医院内分泌科,国家卫生健康委员会内分泌重点实验室,北京100730 [2]哈尔滨医科大学附属第四医院内分泌科,哈尔滨150001 [3]重庆市涪陵中心医院内分泌科,重庆408099 [4]中国人民解放军第八医学中心老年医学科,北京100091 [5]南方医科大学附属第三医院内分泌代谢科,广州510630 [6]洛阳正骨医院(河南省骨科医院)骨质疏松诊疗中心,河南洛阳471002 [7]西安交通大学医学院附属红会医院骨质疏松科,西安710086 [8]天津市天津医院骨内科,天津300299 [9]长春市中心医院内分泌科,长春130041 [10]南京大学医学院附属鼓楼医院骨科,南京210008 [11]山西医科大学第一医院骨科,太原030001 [12]复旦大学附属华东医院骨质疏松科,上海200040 [13]天津医科大学总医院内分泌代谢科,天津300052 [14]重庆医科大学附属第一医院骨科,重庆400042 [15]上海交通大学附属第六人民医院骨质疏松和骨病专科,上海200233 [16]首都医科大学附属北京友谊医院骨科,北京100050 [17]北京大学第一医院医学统计室,北京100034

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2022年第2期142-151,共10页Chinese Journal Of Osteoporosis And Bone Mineral Research

基　　金：中国医学科学院创新工程CIFMS(2016-I2M-3-003,2021-12M-1-002)。

摘　　要：目的 评价金天格胶囊联合阿法骨化醇软胶囊治疗原发性骨质疏松症的有效性及安全性。方法 2016年11月至2019年5月,前瞻性纳入来自全国16个中心原发性骨质疏松症/骨量减少患者,采用分层区组随机方法,随机分配患者至试验组和对照组。两组均给予阿法骨化醇软胶囊,其中试验组口服金天格胶囊和碳酸钙片模拟剂,对照组口服碳酸钙片和金天格胶囊模拟剂,疗程均为52周。以干预52周时的腰椎1-4(L1-4)、股骨颈及全髋骨密度作为主要疗效指标;骨转换标志物[包括血清1型前胶原N-端前肽(procollagen typeⅠN-terminal propeptide,P1NP)、血清1型胶原羧基末端肽(β-C-terminal peptide of typeⅠcollagen,β-CTX)]、临床主要症状评分、疼痛评分及新发骨折与跌倒发生作为次要结局指标。安全性指标包括血尿常规、肝肾功、血钙等血尿生化指标、不良事件发生情况。结果 试验组(金天格胶囊+阿法骨化醇软胶囊)166例及对照组(碳酸钙片+阿法骨化醇软胶囊)168例完成了52周的治疗及随访。两组治疗24周时即观察到L1-4骨密度较基线明显升高,至52周时金天格组与对照组L1-4骨密度仍显著高于基线,分别较治疗前增加0.99%(-1.52%,3.55%)和1.46%(-0.71%,3.81%),均P<0.025。两组骨转换标志物的变化在用药12周时出现,于24周时下降至最低水平,与基线比较差异均有统计学意义(P<0.05)。治疗后两组临床主要症状评分均较基线显著降低,且52周时试验组评分显著低于对照组[2.00(0.00,3.00)vs.3.00(0.00,5.00),P<0.001]。两组疼痛症状评分均有显著改善,且试验组治疗24、36及52周的疼痛评分均低于对照组(P<0.05)。试验组与对照组新发骨折与跌倒发生无显著性差异。两组不良反应发生率无显著性差异,均未出现与研究药物相关的严重不良事件。结论 金天格胶囊联合阿法骨化醇软胶囊治疗能够增加原发性骨质疏松患者的骨密度,其效果�Objective To evaluate the efficacy and safety of Jintiange capsule combined with alfacalcidol soft capsule in the treatment of primary osteoporosis.Methods From November 2016 to May 2019,patients with primary osteoporosis from 16 centers across China were prospectively enrolled.Stratified block randomization was adopted to randomly allocated the participants to the experimental group and the control group.Alfacalcidol soft capsule was given to both groups.The patients in the experimental group were given oral Jintiange capsule and calcium carbonate tablet simulant,while those in the control group were given oral calcium carbonate tablet and Jintiange capsule simulant.The treatment course of both groups were 52 weeks.Bone mineral density(BMD)of lumbar 1-4(L1-4),femoral neck(FN),and total hip(TH)at 52 weeks were used as the primary efficacy endpoint.Bone turnover markers,serum procollagen typeⅠN-terminal propeptide(P1NP)andβ-C-terminal peptide of typeⅠcollagen(β-CTX),clinical major symptom scores,pain scores,and the incidence of new fractures and falls were secondary endpoints.Safety included routine blood and urine,liver and kidney function,blood calcium and other biochemical indicators of blood and urine,and the occurrence of adverse events.Results A total of 166 patients in the experimental group(Jintiange capsule+alfacalcidol soft capsule)and 168 patients in the control group(calcium carbonate tablet+alfacalcidol soft capsule)completed 52 weeks of treatment and follow-up.A significant increase in BMD of L1-4 was observed in both groups at 24 weeks of treatment,and a significant increase in BMD of L1-4 compared with baseline was observed in both experimental group and control group at 52 weeks of treatment[0.99%(-1.52%,3.55%)and 1.46%(-0.71%,3.81%),respectively,all P<0.025].The changes in P1NP andβ-CTX were significant at 12 weeks and decreased to the lowest level at 24 weeks in both groups(P<0.05).The clinical major symptom scores decreased continuously and significantly during the treatment in both grou

关 键 词：金天格胶囊 人工虎骨粉 原发性骨质疏松症 随机对照试验 骨密度 

分 类 号：R681[医药卫生—骨科学]