McClung Michael R
Institute for Health and Ageing, Australian Catholic University, Melbourne, VIC Oregon Osteoporosis Center, 2881 NW Cumberland Road, Portland, OR 97210, USA.
Ther Adv Musculoskelet Dis. 2017 Oct;9(10):263-270. doi: 10.1177/1759720X17726744. Epub 2017 Aug 29.
Sclerostin is an osteocyte-derived glycoprotein that inhibits Wnt/β-catenin signaling and activation of osteoblast function, thereby inhibiting bone formation. It plays a vital role in the regulation of skeletal growth. In adults, sclerostin secretion is modulated by skeletal loading (increased secretion with immobilization; less with weight bearing) and by hormonal/cytokine actions on the osteocyte. Sclerostin deficiency syndromes in humans and animals are characterized by high bone mass of normal quality. In animal models of osteoporosis, inhibition of sclerostin by monoclonal antibodies induces osteoblast activity and new bone formation, normalizing bone mass and improving bone architecture and strength. In recently completed clinical trials, anti-sclerostin antibody therapy results in marked increases in bone mineral density and rapid and substantial reduction in fracture risk. This review will focus on these recent studies and anticipate the role of anti-sclerostin therapy in the management of patients with osteoporosis.
硬化素是一种由骨细胞分泌的糖蛋白，它可抑制Wnt/β-连环蛋白信号传导以及成骨细胞功能的激活，从而抑制骨形成。它在骨骼生长调节中起着至关重要的作用。在成年人中，硬化素的分泌受骨骼负荷（固定不动时分泌增加；负重时分泌减少）以及激素/细胞因子对骨细胞作用的调节。人类和动物的硬化素缺乏综合征的特征是骨质量正常但骨量高。在骨质疏松症动物模型中，单克隆抗体抑制硬化素可诱导成骨细胞活性和新骨形成，使骨量正常化并改善骨结构和强度。在最近完成的临床试验中，抗硬化素抗体疗法可使骨矿物质密度显著增加，并迅速大幅降低骨折风险。本综述将聚焦于这些最新研究，并展望抗硬化素疗法在骨质疏松症患者管理中的作用。
