地诺单抗作用功效

It is a monoclonal antibody targeting RANKL. The drug has been approved by the US FDA for the prevention and treatment of bone metastasis in solid tumors and has also been included in the NCCN guidelines. What are the effects of denosumab?

Role: Denosumab is the first approved monoclonal antibody that specifically targets RANK ligand. RANK ligand is a transmembrane or soluble protein 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. This product has a high affinity with RANKL, prevents RANK ligand from activating RANK on the surface of osteoclasts, inhibits osteoclast activation and development, reduces bone resorption, increases bone density and bone strength of both cortical bone and trabecular bone, promotes bone reconstruction, and reduces the incidence of vertebral, non-vertebral and hip fractures in postmenopausal osteoporotic women. The effect of this product on bone reconstruction can be evaluated by measuring some bone turnover markers (BTMs), such as the bone resorption marker N-telopeptide (NTX), the bone formation marker bone-specific alkaline phosphatase (BSAP), etc. A phase I clinical study conducted in healthy postmenopausal women showed that a dose-dependent decrease in morning urine NTX levels could be observed on day 2 after administration. This decrease could last 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.

Efficacy: Clinical data showed that compared with zoledronic acid, it prolonged the time to first adverse bone event (ARE) in patients by 17%, or significantly delayed the median time to first bone-related event (SRE) by 8.2 months (27.6 months vs. 19.4 months). months), denosumab also extended the time interval between the first episode and the recurrence of SRE by 18% in the study; in addition, for patients with mild or no pain at the time of study enrollment, denosumab also significantly prolonged the time between pain exacerbation compared with zoledronic acid.