抗骨质疏松药物的研究进展
骨质疏松（osteoporosis）是一种最为常见的代谢性骨病,主要表现为骨量减少、骨组织微结构破坏从而导致骨痛、骨脆性及骨折危险性增加。目前临床常用抗骨质疏松药物可分为骨吸收抑制剂、骨形成刺激剂及骨矿化药物。选择性雌激素受体调节剂（SERMs）作为一种新型骨吸收抑制剂,于骨骼系统表现为雌激素激动剂作用,于乳腺等组织表现为雌激素拮抗剂作用,从而不增加致癌风险。骨保护素（OPG）及抗RANKL单克隆抗体可与核因子KB受体活化因子（RANK）竞争结合其配体（RANKL）,从而抑制破骨细胞骨重吸收作用。C-src激酶抑制剂可阻断破骨细胞的细胞内信号转导通路从而不能形成完整的细胞骨架,氯离子通道阻滞剂...
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| Published in | 中国骨质疏松杂志 Vol. 21; no. 3; pp. 367 - 371 |
|---|---|
| Main Author | |
| Format | Journal Article |
| Language | Chinese |
| Published |
重庆医科大学附属第一医院内分泌科,重庆,400016
2015
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1006-7108 |
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| Abstract | 骨质疏松（osteoporosis）是一种最为常见的代谢性骨病,主要表现为骨量减少、骨组织微结构破坏从而导致骨痛、骨脆性及骨折危险性增加。目前临床常用抗骨质疏松药物可分为骨吸收抑制剂、骨形成刺激剂及骨矿化药物。选择性雌激素受体调节剂（SERMs）作为一种新型骨吸收抑制剂,于骨骼系统表现为雌激素激动剂作用,于乳腺等组织表现为雌激素拮抗剂作用,从而不增加致癌风险。骨保护素（OPG）及抗RANKL单克隆抗体可与核因子KB受体活化因子（RANK）竞争结合其配体（RANKL）,从而抑制破骨细胞骨重吸收作用。C-src激酶抑制剂可阻断破骨细胞的细胞内信号转导通路从而不能形成完整的细胞骨架,氯离子通道阻滞剂可破坏破骨细胞骨吸收酸性微环境,αVβ3整合素抗体及其受体拮抗剂可减弱破骨细胞与骨组织粘附,组织蛋白酶K抑制剂可减少骨胶原裂解,从而均有待于成为新一代骨吸收抑制剂。新型骨形成刺激剂主要包括PTH片段制剂、钙离子敏感受体激动剂、骨硬化蛋白中和抗体、他汀类药物等。其中钙离子敏感受体激动剂于成骨细胞可通过促分裂原活化蛋白激酶（MAPK）通路来促进成骨细胞的骨形成作用,于破骨细胞可能通过RANKL信号通路以诱导破骨细胞凋亡。骨硬化蛋白中和抗体可抑制骨硬化蛋白与低密度脂蛋白受体相关蛋白（LRP）5/6结合,从而保证Wnt信号通路在骨形成及重建中发挥作用。他汀类药物则通过增强机体内骨形态发生蛋白-2基因表达以增加骨强度,减少骨折发生。本文就目前新型骨吸收抑制剂及新型骨形成刺激剂的研究进展作一综述。 |
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| AbstractList | R589; 骨质疏松（ osteoporosis ）是一种最为常见的代谢性骨病，主要表现为骨量减少、骨组织微结构破坏从而导致骨痛、骨脆性及骨折危险性增加。目前临床常用抗骨质疏松药物可分为骨吸收抑制剂、骨形成刺激剂及骨矿化药物。选择性雌激素受体调节剂（ SERMs）作为一种新型骨吸收抑制剂，于骨骼系统表现为雌激素激动剂作用，于乳腺等组织表现为雌激素拮抗剂作用，从而不增加致癌风险。骨保护素（ OPG）及抗RANKL单克隆抗体可与核因子KB受体活化因子（ RANK）竞争结合其配体（ RANKL），从而抑制破骨细胞骨重吸收作用。 C-src激酶抑制剂可阻断破骨细胞的细胞内信号转导通路从而不能形成完整的细胞骨架，氯离子通道阻滞剂可破坏破骨细胞骨吸收酸性微环境，αVβ3整合素抗体及其受体拮抗剂可减弱破骨细胞与骨组织粘附，组织蛋白酶K抑制剂可减少骨胶原裂解，从而均有待于成为新一代骨吸收抑制剂。新型骨形成刺激剂主要包括PTH片段制剂、钙离子敏感受体激动剂、骨硬化蛋白中和抗体、他汀类药物等。其中钙离子敏感受体激动剂于成骨细胞可通过促分裂原活化蛋白激酶（ MAPK）通路来促进成骨细胞的骨形成作用，于破骨细胞可能通过RANKL信号通路以诱导破骨细胞凋亡。骨硬化蛋白中和抗体可抑制骨硬化蛋白与低密度脂蛋白受体相关蛋白（ LRP）5／6结合，从而保证Wnt信号通路在骨形成及重建中发挥作用。他汀类药物则通过增强机体内骨形态发生蛋白-2基因表达以增加骨强度，减少骨折发生。本文就目前新型骨吸收抑制剂及新型骨形成刺激剂的研究进展作一综述。 骨质疏松（osteoporosis）是一种最为常见的代谢性骨病,主要表现为骨量减少、骨组织微结构破坏从而导致骨痛、骨脆性及骨折危险性增加。目前临床常用抗骨质疏松药物可分为骨吸收抑制剂、骨形成刺激剂及骨矿化药物。选择性雌激素受体调节剂（SERMs）作为一种新型骨吸收抑制剂,于骨骼系统表现为雌激素激动剂作用,于乳腺等组织表现为雌激素拮抗剂作用,从而不增加致癌风险。骨保护素（OPG）及抗RANKL单克隆抗体可与核因子KB受体活化因子（RANK）竞争结合其配体（RANKL）,从而抑制破骨细胞骨重吸收作用。C-src激酶抑制剂可阻断破骨细胞的细胞内信号转导通路从而不能形成完整的细胞骨架,氯离子通道阻滞剂可破坏破骨细胞骨吸收酸性微环境,αVβ3整合素抗体及其受体拮抗剂可减弱破骨细胞与骨组织粘附,组织蛋白酶K抑制剂可减少骨胶原裂解,从而均有待于成为新一代骨吸收抑制剂。新型骨形成刺激剂主要包括PTH片段制剂、钙离子敏感受体激动剂、骨硬化蛋白中和抗体、他汀类药物等。其中钙离子敏感受体激动剂于成骨细胞可通过促分裂原活化蛋白激酶（MAPK）通路来促进成骨细胞的骨形成作用,于破骨细胞可能通过RANKL信号通路以诱导破骨细胞凋亡。骨硬化蛋白中和抗体可抑制骨硬化蛋白与低密度脂蛋白受体相关蛋白（LRP）5/6结合,从而保证Wnt信号通路在骨形成及重建中发挥作用。他汀类药物则通过增强机体内骨形态发生蛋白-2基因表达以增加骨强度,减少骨折发生。本文就目前新型骨吸收抑制剂及新型骨形成刺激剂的研究进展作一综述。 |
| Abstract_FL | Osteoporosis is the most common metabolic bone disease, characterized by reduced bone mass, damaged microstructure, leading to bone pain and increase of bone frigidity and fracture risk.Commonly used anti-osteoporosis drugs can be classified as anti-resorptive agents, anabolic drugs, and bone mineralization drugs.Selective estrogen receptor modulators ( SERMs) are kind of new anti-resorptive agents.They are estrogen agonist in the bone and antagonist in the breast and other tissues. Osteoprotegerin ( OPG) and anti-RANKL monoclonal antibodies bind to receptor-activator of nuclear factor kappa ligand ( RANKL) to prevent its binding to RANK, hence decreasing the activation of osteoclasts.C-src kinase inhibitors stop osteoclast from forming the integrate cytoskeleton by blocking the signal transduction pathway.Chloride channel inhibitors destroy the acidic environment of bone-resorbing process.Antagonists of αVβ3 integrin receptor decrease the attachment of osteoclasts with bone matrix proteins. Cathepsin K inhibitors reduce the bone collagen degradation.All of them are the new anti-resorptive agents.Upcoming anabolic agents include PTH fragments, calcilytics, antibodies against sclerostin and statins, etc.Among those, calcium-sensing receptor antagonists ( calcilytics) can promote osteoblastic bone formation through the mitogen activated protein kinase ( MAPK) pathway. On the other hand, calcilytics induce osteoclastic apoptosis through the RANKL signal pathway.Monoclonal antibodies against sclerostin inhibit the binding of sclerostin to low density lipoprotein receptor-related protein LRP5 and LRP6, thus ensure the function of Wnt signaling pathway in bone formation and regeneration.Statins increase bone strength and reduce the fracture by enhancing bone morphogenetic protein-2 expression.This paper reviews the current research progress of novel anti-resorptive agents and bone anabolic agents. |
| Author | 崔莹 冯正平 |
| AuthorAffiliation | 重庆医科大学附属第一医院内分泌科,重庆400016 |
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| Author_FL | CUI Ying FENG Zhengping |
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| Author_xml | – sequence: 1 fullname: 崔莹 冯正平 |
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| Keywords | 骨吸收抑制剂 Anti-resorptive agents 骨质疏松 Osteoporosis Progress 骨形成刺激剂 进展 Bone anabolic agents |
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| Notes | Osteoporosis is the most common metabolic bone disease, characterized by reduced bone mass, damaged microstructure, leading to bone pain and increase of bone frigidity and fracture risk. Commonly used anti-osteoporosis drugs can be classified as anti-resorptive agents, anabolic drugs, and bone mineralization drugs. Selective estrogen receptor modulators （SERMs） are kind of new anti-resorptive agents. They are estrogen agonist in the bone and antagonist in the breast and other tissues. Osteoprotegerin （OPG） and anti-RANKL monoclonal antibodies bind to receptor-activator of nuclear factor kappa ligand （RANKL） to prevent its binding to RANK, hence decreasing the activation of osteoclasts. C-src kinase inhibitors stop osteoclast from forming the integrate cytoskeleton by blocking the signal transduction pathway. Chloride channel inhibitors destroy the acidic environment of bone-resorbing process. Antagonists of ctV[33 integrin receptor decrease the attachment of osteoclasts with bone matrix proteins. Cathepsin K |
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| Snippet | ... R589; 骨质疏松（ osteoporosis ）是一种最为常见的代谢性骨病，主要表现为骨量减少、骨组织微结构破坏从而导致骨痛、骨脆性及骨折危险性增加。目前临床常用抗骨质疏松药物可分为骨吸收抑制剂、骨形成刺激剂及骨矿化药物。选择性雌激素受体调节剂（... |
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| SubjectTerms | 进展 骨吸收抑制剂 骨形成刺激剂 骨质疏松 |
| Title | 抗骨质疏松药物的研究进展 |
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