地诺单抗的疗效怎么样呢？

It is the first approved monoclonal antibody specifically targeting RANK ligand. RANK ligand is a transmembrane or soluble protein that is necessary for osteoclasts to maintain their structure, function, and survival. Human RANKL mRNA is mainly found in bones, bone marrow and lymphoid tissues. Its main function in bones is to stimulate the differentiation and activity of osteoclasts and inhibit the apoptosis of osteoclasts. Osteoclasts are responsible for bone resorption, and osteoclast precursors must have low levels of macrophage colony-stimulating factor and RANKL during their differentiation into mature osteoclasts. Denosumab has a high affinity with RANKL, preventing RANK ligand from activating RANK on the surface of osteoclasts, inhibiting osteoclast activation and development, reducing bone resorption, increasing bone density and bone strength of both cortical bone and trabecular bone, promoting bone reconstruction, and reducing the incidence of vertebral, non-vertebral and hip fractures in postmenopausal osteoporotic women.

On May 23, 2018, the U.S. FDA approved a new indication for Amgen’s denosumab, allowing the drug to be used to treat glucocorticoid-induced osteoporosis (GIOP), suitable for male and female patients at high risk of fractures. The decision allows physicians to use the drug in patients with a history of osteoporosis fractures, in patients with multiple risk factors for fractures, or in patients who are ineffective or intolerant of other existing osteoporosis drugs.

How effective is denosumab?

Data from a phase 3 trial showed that patients treated with denosumab experienced greater increases in bone density than those treated with risedronate. The study compared denosumab 60 mg subcutaneously every six months with risedronate 5 mg once daily in two subgroups, those who continued glucocorticoid therapy and those who started glucocorticoid therapy.

The data showed that in the subgroup of patients who received continuous glucocorticoid therapy, risedronate resulted in greater increases in bone density, with increases in bone density occurring at the lumbar spine (4.4% and 2.3%, respectively) and at the hip (2.1% and 0.6%, respectively). In the subgroup of patients who had recently started glucocorticoid therapy, denosumab also induced greater increases in BMD, also in the lumbar spine (3.8% and 0.8%, respectively) and hip (1.7% and 0.2%, respectively).