Therapeutic Drug Review on Romosozumab: The First Sclerostin Inhibitor

Abstract

Osteoporosis is a progressive skeletal disorder which is characterised by low bone mass, normal mineralisation and abnormal bone microarchitecture. This disruption of bone microarchitecture causes subsequent increase in bone fragility and raises risk of fractures. Osteoporosis is a growing public health problem and affects approximately over 200 million people worldwide. In the United Kingdom, it is estimated that around 3 million people have osteoporosis. Since the evolution of drug therapy for osteoporosis in the 1940's with oestrogen therapy several approaches to developing novel therapeutics for osteoporosis in animal studies and clinical observations (e.g., oestrogen, calcitonin, and teriparatide) or opportunistic repurposing of existing compounds (e.g., bisphosphonates) to one driven by advances in fundamental bone biology (e.g., denosumab). The advent of biologic agents has provided a more specific and targeted approach to the treatment of osteoporosis. Sclerostin is a glycoprotein secreted by osteocytes and regulates bone metabolism by inhibiting activation of osteoblast function and bone formation. By inhibiting sclerostin, targeted therapeutic pharmacological agents are being developed to address severe osteoporosis and patients who do not respond well to primary line of medical management of osteoporosis. Romosozumab is humanised as a monoclonal antibody designed to target sclerostin. This review assesses the mechanism and current role of romosozumab in osteoporosis treatment.