Sclerostin: clinical insights in muscle-bone crosstalk

Abstract

Sclerostin, a protein encoded by the sclerostin (SOST) gene, is mostly expressed in osteocytes. First described in the pathogenesis of three disorders, sclerosteosis, van Buchem's disease, and craniodiaphyseal dysplasia, sclerostin has been identified as an important regulator of bone homeostasis, controlling bone formation by osteoblasts through inhibition of the canonical Wnt signaling pathway. Recent studies have highlighted a hypothetical role of sclerostin in myogenesis, thus modulating the interaction between bone and muscle. This narrative review provides an overview of the clinical implications of sclerostin modulation on skeletal muscle mass and function, and bone metabolism. Improving knowledge about muscle-bone crosstalk may represent a turning point in the development of therapeutic strategies for musculoskeletal disorders, particularly osteosarcopenia.

Keywords: Sclerostin; Wnt-pathway; falls; muscle mass; muscle strength; myoblasts; osteocytes; osteoporosis; osteosarcopenia; romosozumab.

Figure 1.

Overview of the effects of sclerostin on bone and muscle. Sclerostin blocks the Wnt pathway, the latter having bone protective effects by reducing receptor activator of nuclear factor-kB ligand (RANK-L) production, increasing osteoprotegerin (OPG) production and transcription of genes for osteoblasts survival and activity; moreover, the Wnt pathway also positively acts on skeletal muscle, by increasing myoblast differentiation and reducing satellite cell quiescence, thus improving muscle mass and function. Thus, modulation of the Wnt pathway through the block of sclerostin might counteract osteosarcopenia and its clinical consequences.