Sclerostin monoclonal antibody therapy with AMG 785: a potential treatment for osteoporosis

Importance of the field: Osteoporosis is a common skeletal disease characterized by loss of bone strength that leads to increased risk of fractures. Fractures of the hip and spine are associated with disability, increased risk of death and high healthcare costs. Recent improvement in the understanding of the molecular regulators of bone metabolism has led to the investigation and development of new therapeutic agents with novel mechanisms of action that may offer advantages over currently available treatments for osteoporosis. Areas covered in this review: Sclerostin is a small protein secreted by osteocytes that downregulates osteoblast-mediated bone formation. This is a review of the rationale, mechanism of action, preclinical and clinical development of AMG 785 (CDP7851), an investigational humanized mAb that inhibits the activity of sclerostin, resulting in increased bone formation. What the reader will gain: The reader will gain an insight into the potential use of sclerostin mAb therapy for the treatment of osteoporosis. Take home message: Preclinical studies and an early report of a clinical study suggest that inhibition of sclerostin with AMG 785 may provide skeletal benefit for patients with osteoporosis.