国产rhPTH1-34治疗绝经后骨质疏松症的有效性和安全性:随机对照、多中心临床研究  

Efficacy and safety of domestic recombinant human parathyroid hormone N⁃terminal 1⁃34 fragment in the treatment of postmenopausal osteoporosis:a randomized,controlled,multicenter study

作　　者：李梅 章振林[2] 林华[3] 程群 屠重棋[5] 唐海[6] 游利[7] 郑淑慧[8] 徐勉[9] 金小岚 余卫[11] 胡伟伟[2] 朱秀芬[3] 朱汉民 石锐[5] 陈浩[6] 陈琳[7] 高尚聚[8] 杜鹃 程莹 夏维波 LI Mei;ZHANG Zhen-lin;LIN Hua;CHENG Qun;TU Chong-qi;TANG Hai;YOU Li;ZHENG Shu-hui;XU Mian;JIN Xiao-lan;YU Wei;HU Wei-wei;ZHU Xiu-fen;ZHU Han-min;SHI Rui;CHEN Hao;CHEN Lin;GAO Shang-ju;DU Juan;CHENG Ying;XIA Wei-bo(Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Key Laboratory of Endocrinology of National Health Commission,Beijing 100730, China;Department of Osteoporosis and Bone Disease, Shanghai Jiao Tong University Affiliated Six People's Hospital, Shanghai 200233, China;Department of Orthopaedics, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, China;Department of Osteoporosis and Bone Disease, Huadong Hospital Afliated to Fudan University, Shanghai 200040, China;Department of Orthopedics, West China Hospital, Sichuan University, Chengdu 610047, China;Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China;Department of Endocrinology and Metabolism, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China;Department of Orthopaedics, Heibei General Hospital, Shijiazhuang 050051, China;Department of Endocrinology, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, China;Department of Endocrinology, Western Theater Command General Hospital, Chengdu 610083, China;Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China)

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]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 [3]南京大学医学院附属鼓楼医院骨科,南京210008 [4]复旦大学附属华东医院骨质疏松科,上海200040 [5]四川大学华西医院骨科,成都610047 [6]首都医科大学附属北京友谊医院骨科,北京100050 [7]上海市第一人民医院内分泌科,上海200080 [8]河北省人民医院骨科,石家庄050051 [9]昆明医科大学第二附属医院内分泌科,昆明650101 [10]中国人民解放军西部战区总医院内分泌科,成都610083 [11]中国医学科学院,北京协和医学院,北京协和医院放射科,北京100730

出　　处：《中华骨质疏松和骨矿盐疾病杂志》2022年第2期135-141,共7页Chinese Journal Of Osteoporosis And Bone Mineral Research

摘　　要：目的 以原研特立帕肽和鲑鱼降钙素为阳性对照,观察国产基因重组人甲状旁腺素氨基端1-34片段(recombinant human parathyroid hormone N-terminal 1-34 fragment,rhPTH1-34)治疗绝经后骨质疏松症的有效性和安全性。方法 纳入绝经后骨质疏松症女性214例,按照1∶1∶1∶0.5比例,随机分为4组:rhPTH1-3420μg组(n=59)及40μg组(n=62)分别每天注射国产rhPTH1-3420及40μg;降钙素组(n=61)给予鼻喷鲑鱼降钙素200 IU;特立帕肽组(n=32)给予原研特立帕肽注射20μg/d;疗程均为24周。观察治疗前后腰椎(L1-4)和髋部骨密度(bone mineral density,BMD)的变化率,骨转换生化指标的变化率,包括血清Ⅰ型前胶原N-端肽(procollagen typeⅠN-terminal propeptide,P1NP)和Ⅰ型胶原交联C-末端肽(β-cross linked C-telopeptide of typeⅠcollagen,β-CTX),以及药物治疗的安全性。结果 治疗24周后,rhPTH1-3420μg及40μg组L1-4 BMD较基线分别增加3.42%和4.82%,特立帕肽组L1-4 BMD增加3.66%(均P<0.05),rhPTH1-34治疗组间骨密度变化率无明显差异;降钙素组腰椎骨密度变化率为-0.01%,骨密度无明显增加(P>0.05)。国产及原研特立帕肽的疗效均优于鼻喷降钙素组。国产与原研rhPTH1-3420μg组治疗24周使血清P1NP分别升高534.22%和277.86%,使β-CTX水平分别升高247.88%和202.25%(均P<0.001),P1NP增幅大于β-CTX。国产与原研rhPTH1-34组的安全性较好。结论 每天皮下注射20μg国产rhPTH1-34治疗24周能够显著提升腰椎BMD,促进骨形成,疗效及安全性与原研特立帕肽相当,且优于降钙素鼻喷剂。Objective To evaluate the efficacy and safety of domestic and original recombinant human parathyroid hormone N-terminal 1-34 fragment(rhPTH1-34)and salmon calcitonin in the treatment of postmenopausal osteoporosis.Methods A total of 214 postmenopausal women with osteoporosis were randomly divided into 4 groups of subcutaneous injection of domestic rhPTH1-3420μg(n=59)and 40μg(n=62),original rhPTH1-34(teriparatide)20μg(n=32),and nasal spray of salmon calcitonin 200 IU(n=61)daily.The treatment duration was 24 weeks.The change rates of bone mineral density(BMD)at lumbar spine(L1-4)and total hip were evaluated during the treatment.The change rates of bone turnover biomarkers,including procollagen type I N-terminal propeptide(P1NP)andβ-cross linked C-telopeptide of type I collagen(β-CTX),the incidence of fracture,the safety index was assessed during the treatment.Results After 24 weeks of treatment,compared with baseline,the L1-4 BMD in domestic rhPTH1-3420μg and 40μg groups increased by 3.42%and 4.82%,respectively,and the L1-4 BMD of original rhPTH1-3420μg groups increased by 3.66%(all P<0.05 compared with baseline),without significant difference in the change rate of L1-4 BMD among groups of rhPTH1-34.There was no significant increase in BMD at lumbar spine in calcitonin group(rates of change in BMD:-0.01%,P>0.05).The levels of serum P1NP were increased by 534.22%and 277.86%,andβ-CTX level was elevated by 247.88%and 202.25%after 24 weeks of domestic and original rhPTH1-3420μg treatment(all P<0.001 compared with baseline),and the increase of P1NP was greater than that ofβ-CTX.The safety of domestic and original rhPTH1-34 was quite well.Conclusions Domestic rhPTH1-3420μg treatment for 24 weeks can significantly improve lumbar BMD,and stimulate bone formation.The efficacy and safety of domestic rhPTH1-34 are equivalent to the original teriparatide,which are better than calcitonin nasal spray.

关 键 词：甲状旁腺素氨基端1-34片段 特立帕肽 绝经后骨质疏松 骨密度 

分 类 号：R681[医药卫生—骨科学] R972[医药卫生—外科学]