Deal Chad
Center for Osteoporosis and Metabolic Bone Disease, Department of Rheumatology, Orthopedic and Rheumatology Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Curr Opin Rheumatol. 2009 Jul;21(4):380-5. doi: 10.1097/BOR.0b013e32832cbc2a.
To describe new agents for the treatment of osteoporosis, discuss a conceptual framework of agents that are antiresorptive or anabolic, and review pathways that affect bone turnover and steps in those pathways that are targets for new therapeutic agents.
Novel antiresorptive agents are being developed. Denosumab, a fully human mononoclonal antibody to receptor activator of nuclear factor kappa B ligand, has completed its major fracture trial. Assessment of odanacatib, an inhibitor of cathepsin K, an osteoclast enzyme required for resorption of bone matrix, is underway. Glucagon-like peptide 2 is an intestinal peptide that prevents the nocturnal rise in bone resorption. Anabolic agents act by stimulating new bone formation. Novel anabolic agents in development include antibodies that target molecules (sclerostin and Dkk1) involved in Wnt signaling, a pathway that regulates gene transcription of proteins that are important for osteoblast function. An antagonist to the calcium-sensing receptor and an activin receptor fusion protein, which functions as an activin antagonist, have shown promise as anabolic agents in early human trials.
This review discusses potential future advances in drug therapy for osteoporosis including novel antiresorptive and anabolic agents that may become available in the coming years.
描述治疗骨质疏松症的新型药物，讨论抗吸收或促合成药物的概念框架，并回顾影响骨转换的途径以及这些途径中作为新型治疗药物靶点的步骤。
新型抗吸收药物正在研发中。地诺单抗是一种针对核因子κB受体活化因子配体的全人单克隆抗体，已完成其主要骨折试验。组织蛋白酶K抑制剂奥达卡替布正在进行评估，组织蛋白酶K是骨基质吸收所需的破骨细胞酶。胰高血糖素样肽2是一种肠道肽，可防止夜间骨吸收增加。促合成药物通过刺激新骨形成发挥作用。正在研发的新型促合成药物包括靶向参与Wnt信号通路的分子（硬化蛋白和Dickkopf-1）的抗体，Wnt信号通路调节对成骨细胞功能重要的蛋白质的基因转录。钙敏感受体拮抗剂和激活素受体融合蛋白（作为激活素拮抗剂发挥作用）在早期人体试验中已显示出作为促合成药物的前景。
本综述讨论了骨质疏松症药物治疗未来可能的进展，包括未来几年可能上市的新型抗吸收和促合成药物。
