Abstract
Osteoporosis, a widespread skeletal disorder with a substantial economic load, is characterized by increased porosity of the bones resulting in vulnerability to fractures. When activated, the canonical Wnt signaling pathway results in osteoblastogenesis and bone formation. A Wnt ligand forms a complex with low-density lipoprotein receptor-related proteins 5 and 6 (Lrp5/6) and stimulates intracellular signaling cascades, leading to nuclear translocation of β-catenin and transcription of downstream molecules involved in osteoblast differentiation, maturation, and survival. Sclerostin (SOST), a glycoprotein produced by osteocytes, is an extracellular Wnt antagonist that blocks the binding of Wnt ligands to Lrp5/6, preventing the activation of the pathway and osteoblast-mediated bone formation subsequently. Inhibition of SOST represents a new therapeutic paradigm for the treatment of osteoporosis. Monoclonal antibodies to SOST include romosozumab, blosozumab, and setrusumab. With its unique dual effect of increasing bone formation (anabolic action) and decreasing bone resorption, the Food and Drug Administration approved romosozumab, a promising new treatment for postmenopausal osteoporosis. Its efficacy and safety have been established in trials. However, patients at high risk of cardiovascular or cerebrovascular events should not be prescribed romosozumab.