Introduction: Disorders with inactivating mutations of the SOST gene result in reduced or absent expression of sclerostin and are associated with high bone mass. Sclerostin is an important regulator of bone formation due to its inhibitory actions in the osteoanabolic Wnt signaling pathway. Advances in understanding the mechanisms of action of this signaling molecule have led to the development of a pharmacological inhibitor of sclerostin with potential clinical applications as an osteoanabolic drug for the treatment of osteoporosis.
Areas covered: Romosozumab is the first humanized monoclonal sclerostin antibody to be tested in clinical trials. Similar to preclinical animal studies with sclerostin antibodies, initial clinical studies show that romosozumab increases bone formation and bone mineral density.
Expert opinion: Blocking sclerostin action with romosozumab is a promising new therapeutic approach to osteoanabolic therapy of osteoporosis; efficacy and safety data on large controlled studies are awaited.