The Role of Sclerostin in the Pathophysiology of Sclerosing Bone Dysplasias

In the last decade, osteocyte-produced sclerostin has emerged as a key regulator of bone remodeling. Sclerostin inhibits bone formation and may also stimulate bone resorption. Impaired sclerostin synthesis leads to generalized hyperostosis, particularly of the skull bones, in patients with sclerosteosis and van Buchem disease due to unrestrained bone formation. The synthesis of sclerostin is controlled by systemic and local factors, and aberrant sclerostin synthesis has been reported in several disorders of bone and mineral metabolism. The restricted expression of sclerostin in bone, the excellent quality of bone of patients with sclerosteosis and van Buchem disease and the lack of abnormalities in organs other than the skeleton in these patients have made sclerostin a promising target for new bone-building therapies for osteoporosis.