地诺单抗好用吗？

It is approved for the prevention of bone-related events in patients with bone metastases from solid tumors. It is not indicated for the prevention of bone-related events in patients with multiple myeloma, or for the treatment of hypercalcemia in adults or bone-mature adolescents with giant cell tumors of bone who are unresectable or surgically resectable malignancies that may cause serious complications and are bisphosphonate-resistant.

Denosumab is the first approved monoclonal antibody that specifically targets 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. The effect of denosumab on bone reconstruction can be evaluated by measuring some bone renewal markers, such as the bone resorption marker N-telopeptide, the bone formation marker bone-specific alkaline phosphatase, etc. A phase I clinical study conducted in healthy postmenopausal women showed that a dose-dependent decrease in morning urine NTX levels was observed on day 2 after administration. This decrease lasted for 6 months, with the maximum decrease reaching 84% compared with baseline. This effect is reversible. When serum denosumab levels disappear, NTX levels can be seen to rise again, which reflects the reversibility of its effect on bone reconstruction. As treatment continues, these effects will persist for a new cycle.

Based on multiple trial data, denosumab was approved by the FDA on November 18, 2010. Up to now, it is approved for the prevention of bone-related events with bone metastasis of solid tumors. It is not used for the prevention of bone-related events in patients with multiple myeloma. It is used for the prevention of bone-related events in adults or bone-mature adolescents with giant cell tumors of bone that are unresectable or where surgical resection may cause serious complications. It is not used for hypercalcemia of malignant tumors.