Alhumaid Ibrahim, Abu-Zaid Ahmed
Orthopaedics, Alfaisal University College of Medicine, Riyadh, SAU.
Oncology, Alfaisal University College of Medicine, Riyadh, SAU.
Cureus. 2019 Jan 31;11(1):e3989. doi: 10.7759/cureus.3989.
Aneurysmal bone cysts (ABCs) are uncommon lesions that involve the axial and appendicular bones. Although biologically benign, ABCs have the tendency to assume an aggressive behavior causing local destruction of the underlying bone and neighboring soft tissues. Morphologically, ABCs are composed of cyst-like cavities filled with blood and bounded by an array of diverse cells including fibroblasts, inflammatory infiltrates and osteoclast-like multinucleated giant cells. From a molecular perspective, the osteoclast-like multinucleated giant cells harbor high expression of receptor activator of nuclear factor kappa B (RANK) receptors, whereas the neoplastic stromal cells harbor high expression of RANK ligand (RANKL). The RANK-RANKL interaction has been implicated in the carcinogenesis of ABCs and giant cell tumor of bones (GCTBs). Currently, the optimal management of ABCs remains a hotly debated topic. There are a multitude of treatment modalities (that is, surgery, sclerotherapy, radiotherapy and selective arterial embolization), and each modality has its own benefits, morbidity and risk of complications. The local aggressiveness of ABC and its high rates of relapse following treatment has demanded the march towards discovering more innovative therapies. One of such therapies is denosumab, a monoclonal antibody targeted against the RANKL. Denosumab is already approved by the United States Food and Drug Administration (FDA) for the treatment of adults and skeletally mature adolescents with GCTB that is unamenable to surgery, or initial surgery is anticipated to result in significant morbidity. However, denosumab is not approved by the FDA for the management of ABCs. However, taking into consideration the morphological similarity between GCTBs and ABCs, some treating physicians have logically opted to use denosumab in an off-label manner to treat select ABCs. To the best of knowledge, no study has attempted to summarize the related literature on the use of denosumab in ABCs. Therefore, the primary aim of this study is to narratively review all the available literature about the efficacy and safety of the use of off-label denosumab in the management of patients with ABCs.
动脉瘤样骨囊肿（ABCs）是一种累及中轴骨和四肢骨的罕见病变。尽管ABCs在生物学上是良性的，但它们往往表现出侵袭性，可导致其下方骨骼和邻近软组织的局部破坏。在形态学上，ABCs由充满血液的囊样腔隙组成，周围有一系列不同的细胞，包括成纤维细胞、炎症浸润细胞和破骨细胞样多核巨细胞。从分子角度来看，破骨细胞样多核巨细胞高表达核因子κB受体激活剂（RANK）受体，而肿瘤性基质细胞高表达RANK配体（RANKL）。RANK-RANKL相互作用与ABCs和骨巨细胞瘤（GCTBs）的致癌作用有关。目前，ABCs的最佳治疗方案仍是一个备受争议的话题。有多种治疗方式（即手术、硬化疗法、放疗和选择性动脉栓塞），每种方式都有其自身的益处、发病率和并发症风险。ABC的局部侵袭性及其治疗后较高的复发率促使人们寻求更多创新疗法。其中一种疗法是地诺单抗，一种靶向RANKL的单克隆抗体。地诺单抗已被美国食品药品监督管理局（FDA）批准用于治疗无法进行手术或预计初次手术会导致严重并发症的成年和骨骼成熟青少年GCTB患者。然而，FDA未批准地诺单抗用于ABCs的治疗。不过，考虑到GCTBs和ABCs在形态学上的相似性，一些治疗医生合理地选择以非标签方式使用地诺单抗来治疗某些ABCs。据我们所知，尚无研究试图总结关于地诺单抗用于ABCs的相关文献。因此，本研究的主要目的是叙述性综述所有关于非标签使用地诺单抗治疗ABCs患者的疗效和安全性的现有文献。
