狄诺塞麦对骨转移有多大疗效？

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. 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.

Denosumab was approved by the FDA in 2009 to treat postmenopausal osteoporosis, and is used to treat bone destruction caused by breast cancer, prostate cancer bone metastasis, and multiple myeloma.

So how effective is denosumab on bone metastasis?

Clinical data showed that compared with zoledronic acid, denosumab prolonged the time to the first adverse bone event (ARE) in patients by 17%, or significantly delayed the median time to the first bone-related event (SRE) by 8.2 months (27.6 months vs. 19.4 months). months), denosumab also extended the time interval from the first episode to the recurrence of SRE by 18% in the study; in addition, for patients with mild or no pain when enrolled in the study, compared with zoledronic acid, (denosumab) can also significantly extend the time interval between pain exacerbation, which shows that the therapeutic effect of denosumab is very good.