Varenna M, Gatti D
Centro per la Diagnosi e la Terapia delle Patologie Osteometaboliche, U.O.C. Day Hospital di Reumatologia, Dipartimento di Reumatologia, Istituto Gaetano Pini, Milano, Italia.
Reumatismo. 2010 Jul-Sep;62(3):163-71. doi: 10.4081/reumatismo.2010.163.
Osteoporosis is a skeletal disease affecting millions of people worldwide in which a decreased bone mass and a microarchitectural deterioration compromise bone strength leading to bone fragility and increased susceptibility to fracture. Bone turnover increases at menopause, with osteoclast-mediated bone resorption exceeding bone formation. Recent discoveries in bone biology have demonstrated that RANKL, a cytokine member of the tumor necrosis factor superfamily, is an essential mediator of osteoclast formation, function and survival. Denosumab is a fully human monoclonal antibody with a high affinity and specificity for human RANKL. By binding to its target, denosumab prevents the interaction of RANKL with its receptor RANK on osteoclasts and their precursors and inhibits osteoclast-mediated bone resorption. Administered as a subcutaneous injection every six months, denosumab has been shown to decrease bone turnover and to increase bone mineral density in postmenopausal women with low bone mass and osteoporosis. In these patients denosumab significantly reduced the risk of vertebral fractures, hip fractures and nonvertebral fractures. In all clinical trials published to date, denosumab was well tolerated with an incidence of adverse events, including infections and malignancy, generally similar to subjects receiving placebo or alendronate. The denosumab therapeutic regimen consisting in a subcutaneous injection every 6 months may increase patient compliance and persistence with a further benefit from treatment. By providing a new molecular target for osteoporosis treatment, denosumab is a promising drug for the treatment of postmenopausal osteoporosis and the prevention of fragility fractures.
骨质疏松症是一种影响全球数百万人的骨骼疾病,骨量减少和微结构恶化会损害骨骼强度,导致骨骼脆弱并增加骨折易感性。绝经时骨转换增加,破骨细胞介导的骨吸收超过骨形成。骨生物学的最新发现表明,肿瘤坏死因子超家族的细胞因子成员RANKL是破骨细胞形成、功能和存活的重要介质。地诺单抗是一种对人RANKL具有高亲和力和特异性的全人单克隆抗体。通过与其靶点结合,地诺单抗可阻止RANKL与其在破骨细胞及其前体上的受体RANK相互作用,并抑制破骨细胞介导的骨吸收。每六个月皮下注射一次地诺单抗,已显示可降低骨量低和患有骨质疏松症的绝经后妇女的骨转换并增加骨密度。在这些患者中,地诺单抗显著降低了椎体骨折、髋部骨折和非椎体骨折的风险。在迄今发表的所有临床试验中,地诺单抗耐受性良好,不良事件发生率(包括感染和恶性肿瘤)通常与接受安慰剂或阿仑膦酸盐的受试者相似。每6个月皮下注射一次的地诺单抗治疗方案可能会提高患者的依从性和持续性,从而进一步从治疗中获益。通过为骨质疏松症治疗提供新的分子靶点,地诺单抗是治疗绝经后骨质疏松症和预防脆性骨折的一种有前景的药物。