First Department of Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Department of Endocrinology and Diabetes and Department of Medical Research, 251 Hellenic Air Force General Hospital, Athens, Greece.
Bone. 2019 Dec;129:115048. doi: 10.1016/j.bone.2019.115048. Epub 2019 Aug 24.
Denosumab (Dmab), a monoclonal antibody against the receptor activator of nuclear factor-κB (RANK) ligand (RANKL) which substantially suppresses osteoclast activity, has been approved for the treatment of common metabolic bone diseases, including postmenopausal osteoporosis, male osteoporosis, and glucocorticoid-induced osteoporosis, in which the pathway of the RANK/RANKL/osteoprotegerin is dysregulated. However, the imbalance of RANKL/RANK/osteoprotegerin is also implicated in the pathogenesis of several other rare metabolic bone diseases, including Juvenile Paget disease, fibrous dysplasia, Hajdu Cheney syndrome and Langerhans cell histiocytosis, thus rendering Dmab a potential treatment option for these diseases. Dmab has been also administered off-label in selected patients (e.g., with Paget's disease, osteogenesis imperfecta, aneurysmal bone cysts) due to contraindications or unresponsiveness to standard treatment, such as bisphosphonates. Moreover, Dmab was administered to improve hypercalcemia induced by various diseases, including primary hyperparathyroidism, tuberculosis and immobilization. The aim of this review is to summarize existing evidence on off-label uses of Dmab in metabolic bone diseases and provide opinion for or against its use, which should be always considered on an individual basis.
地舒单抗（Dmab）是一种针对核因子-κB 受体激活剂配体（RANKL）的单克隆抗体，可显著抑制破骨细胞活性，已被批准用于治疗常见代谢性骨病，包括绝经后骨质疏松症、男性骨质疏松症和糖皮质激素诱导的骨质疏松症，其中 RANK/RANKL/骨保护素途径失调。然而，RANKL/RANK/骨保护素的失衡也与其他几种罕见代谢性骨病的发病机制有关，包括青少年佩吉特病、纤维结构不良、哈杰奇-切尼综合征和朗格汉斯细胞组织细胞增生症，从而使 Dmab 成为这些疾病的潜在治疗选择。由于禁忌证或对标准治疗（如双膦酸盐）无反应，Dmab 已被超适应证用于某些患者（例如，患有佩吉特病、成骨不全症、动脉瘤样骨囊肿）。此外，Dmab 还被用于改善由各种疾病引起的高钙血症，包括原发性甲状旁腺功能亢进症、结核病和固定。本综述的目的是总结 Dmab 在代谢性骨病中超适应证使用的现有证据，并对其使用提出赞成或反对的意见，应始终根据个体情况考虑。
