The role of the Wnt-Inhibitors Sclerostin and Dickkopf-1 in bone disorders

Bone undergoes continuous remodeling by the tightly coordinated activities of both bone resorbing osteoclasts as well as osteoblasts which produce new mineralized bone matrix. An imbalance of these cell types is a hallmark of numerous metabolic bone disorders. The Wnt pathway plays a key role in bone remodeling by promoting the differentiation of osteoblasts. Dickkopf-1 (DKK-1) and Sclerostin represent two potent inhibitors of the Wnt pathway thereby mediating a finetuning of osteoblastogenesis. The biological function of these proteins is well characterized and both are detectable as biomarkers in humans by sensitive assays. Current pre clinical and clinical studies point to the potential therapeutic benefit by targeting DKK-1 and Sclerostin in bone disorders that are accompanied by the loss of bone mass and an increased fracture risk.