Anti-sclerostin antibodies: Utility in treatment of osteoporosis

Abstract

Monoclonal antibodies to molecular targets important for bone formation and bone resorption are being investigated for treatment of postmenopausal osteoporosis. Postmenopausal osteoporosis is characterized by increased bone turnover, with bone resorption typically exceeding bone formation. These pathophysiological changes cause decreased bone mineral density and disruption of bone microarchitecture which lead to low-trauma fractures.Sclerostin is a glycoprotein inhibitor of osteoblast Wnt signaling produced by osteocytes that has been recognized as a new target for therapeutic intervention in patients with osteoporosis. Sclerostin was first recognized when disorders with inactivating mutations of the sclerostin gene SOST were found to be associated with high bone mass. These observations suggested that inhibitors of sclerostin might be used to increase bone mineral density.Romosozumab (AMG 785) is the first humanized anti-sclerostin monoclonal antibody that has been demonstrated to increase bone formation. This investigational monoclonal antibody, and blosozumab, another investigational anti-sclerostin antibody, have osteoanabolic properties with the potential to improve clinical outcomes in patients with osteoporosis. Similar to preclinical animal studies with sclerostin antibodies, initial clinical studies have shown that romosozumab increases bone formation and BMD. Further evaluation of the efficacy and safety of this agent in a large phase III controlled study is awaited. Phase I clinical trial data have recently been published with blosozumab. These novel interventions appear to be promising agents for the treatment of osteoporosis.