Pharmacotherapy of osteoporosis 2

Published on August 31, 2015   41 min

Other Talks in the Series: Bone in Health and Disease

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Let's just turn and discuss denosumab. This is one of the newer treatments for osteoporosis, and its availability grew out of new understanding of the molecular control and modulation of bone remodeling. As you're aware, RANK Ligand is a protein secreted by osteoblasts and osteoclasts. The action to RANK LIGAND is necessary for the activation and proliferation of osteoclasts. Denosumab is a fully human monoclonal antibody that binds to and then activates RANK Ligand. And as a result, denosumab therapy inhibits the differentiation proliferation and activity of osteoclasts and substantially reduces bone resorption. As with bisphosphonates because of a decrease number in activity of osteoclasts, the feedback to osteoblast is reduced, and there is a secondary inhibition bone formation as well. The pharmacokinetics of denosumab, which is given subcutaneously, is complex. One dose of 60 milligrams or greater reduces bone turnover for at least six months. In the studies that have been performed, denosumab therapy results in a progressive increase in bone mineral density over at least the first eight years of therapy, different and greater in magnitude than we observe with bisphosphonate therapy. Because of the pharmacokinetics, once therapy is discontinued, there's a very rapid and complete reversal of the effects on bone remodeling within just a few weeks of missing the every six-month dose.