Appelman-Dijkstra Natasha M, Papapoulos Socrates E
Center for Bone Quality, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
Calcif Tissue Int. 2016 Apr;98(4):370-80. doi: 10.1007/s00223-016-0126-6. Epub 2016 Mar 26.
The recognition of the importance of the Wnt-signaling pathway in bone metabolism and studies of patients with rare skeletal disorders characterized by high bone mass identified sclerostin as target for the development of new therapeutics for osteoporosis. Findings in animals and humans with sclerostin deficiency as well as results of preclinical and early clinical studies with sclerostin inhibitors demonstrated a new treatment paradigm with a bone building agent for the management of patients with osteoporosis, the antifracture efficacy, and long-term tolerability of which remain to be established in on-going phase III clinical studies. In this article we review the currently available preclinical and clinical evidence supporting the use of sclerostin inhibitors in osteoporosis.
Wnt信号通路在骨代谢中的重要性得到认可,对以高骨量为特征的罕见骨骼疾病患者的研究确定了硬化素是开发骨质疏松症新疗法的靶点。硬化素缺乏的动物和人类研究结果以及硬化素抑制剂的临床前和早期临床研究结果表明,一种用于治疗骨质疏松症患者的骨形成药物的新治疗模式,其抗骨折疗效和长期耐受性仍有待正在进行的III期临床研究确定。在本文中,我们综述了目前支持在骨质疏松症中使用硬化素抑制剂的临床前和临床证据。