Bogado Cesar E, Boailchuk J A, Zanchetta M B, Massari F E, Zanchetta J R
Instituto de Investigaciones Metabólicas, Buenos Aires, Argentina.
Drugs Today (Barc). 2011 Aug;47(8):605-13. doi: 10.1358/dot.2011.47.8.1603507.
Denosumab is a fully human monoclonal antibody that inhibits the formation, function and survival of osteoclasts, preventing the interaction of tumor necrosis factor ligand superfamily member 11 (receptor activator of nuclear factor kappa-B ligand, RANKL) with the tumor necrosis factor receptor superfamily member 11A (osteoclast differentiation factor receptor, ODFR, receptor activator of NF-KB, RANK). This results in a reduction in bone resorption and an increase in bone mineral density. In clinical studies, denosumab has been shown to decrease the risk for vertebral, hip and nonvertebral fractures in women with postmenopausal osteoporosis and the risk for new vertebral fractures in men with nonmetastatic prostate cancer receiving androgen deprivation therapy, with a rate of side effects similar to placebo. A number of clinical trials with denosumab are ongoing to demonstrate its value for other indications and to further characterize its effects on immunomodulation. Denosumab is a new alternative for the prevention and treatment of postmenopausal osteoporosis and a promising agent for the treatment of other bone diseases associated with bone loss.
地诺单抗是一种完全人源化单克隆抗体,可抑制破骨细胞的形成、功能及存活,阻止肿瘤坏死因子配体超家族成员11(核因子κB受体活化因子配体,RANKL)与肿瘤坏死因子受体超家族成员11A(破骨细胞分化因子受体,ODFR,核因子κB受体活化因子,RANK)相互作用。这会导致骨吸收减少及骨矿物质密度增加。在临床研究中,地诺单抗已被证明可降低绝经后骨质疏松症女性发生椎体、髋部和非椎体骨折的风险,以及接受雄激素剥夺治疗的非转移性前列腺癌男性发生新椎体骨折的风险,其副作用发生率与安慰剂相似。多项关于地诺单抗的临床试验正在进行,以证明其对其他适应症的价值,并进一步明确其对免疫调节的影响。地诺单抗是预防和治疗绝经后骨质疏松症的新选择,也是治疗其他与骨质流失相关骨病的有前景药物。