狄诺塞麦作用及功效

On May 28, 2010, the European Commission approved the treatment of bone loss associated with hormone suppression in postmenopausal women with osteoporosis and prostate cancer. It can also be used in patients who are currently ineffective or intolerant to other treatments to reduce the risk of fractures. Denosumab was approved for the first time in 27 EU member states, as well as Norway, Iceland, and Liechtenstein. In June of the same year, this product was approved by the FDA for marketing.

What are the functions and effects of denosumab?

The main mechanism and efficacy of denosumab: The most important signaling pathway in regulating osteoclast differentiation and regulating osteoclast activity is the OPG/RANKL/RANK pathway. RANK is a human cell nuclear factor κB receptor activator, expressed in osteoclasts (OC) and osteoclast precursor cells; RANKL is a nuclear factor κB receptor activator ligand, a member of the tumor necrosis factor α receptor superfamily, and is mainly expressed in osteoblasts. RANKL mediates OC maturation and function through RANK. Osteoprotegerin (OPG) is a soluble receptor secreted by osteoblasts that competitively binds RANKL to RANK, thereby inhibiting bone resorption.

Denosumab is a monoclonal antibody of RANKL, which also belongs to the tumor necrosis factor α family. It is expressed and secreted by Chinese hamster ovary cells (CHO cells). It is a non-cytotoxic IgG2 monoclonal antibody, also known as AMG162. Its mechanism of action is similar to osteoprotegerin (OPG). Denosumab can compete with RANK to bind to the DE ring structure on the human RANKL protein. On the one hand, it activates nuclear factor κB and the latter enters the nucleus to affect the expression of related genes.

It plays a key role in the activation, differentiation, proliferation, multinucleation and survival of osteoclasts; on the other hand, it can inhibit the binding of RANKL to RANK on the surface of osteoclasts and their precursors, effectively blocking the interaction between ligands and receptors. Thereby inhibiting the formation, function and survival of activated osteoclasts, reducing osteoclast activity, inhibiting osteoclast differentiation, thereby inhibiting the bone resorption process, reducing osteolysis, improving bone density, increasing bone strength, and hindering tumor growth.