Terpos E, Christoulas D, Gavriatopoulou M, Dimopoulos M A
Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Alexandra General Hospital, Athens, Greece.
Eur J Cancer Care (Engl). 2017 Nov;26(6). doi: 10.1111/ecc.12761. Epub 2017 Sep 21.
Osteolytic bone disease is a frequent complication of multiple myeloma, resulting in skeletal complications that are a significant cause of morbidity and mortality. It is the result of an increased activity of osteoclasts, which is not followed by reactive bone formation by osteoblasts. Recent studies have revealed novel molecules and pathways that are implicated in osteoclast activation and osteoblast inhibition. Among them, the most important include the receptor activator of nuclear factor-kappa B ligand/osteoprotegerin pathway, the macrophage inflammatory proteins and the activin-A that play a crucial role in osteoclast stimulation in myeloma, while the wingless-type (Wnt) signalling inhibitors (sclerostin and dickkopf-1) along with the growth factor independence-1 are considered the most important factors for the osteoblast dysfunction of myeloma patients. Finally, the role of osteocytes, which is the key cell for normal bone remodelling, has also revealed during the last years through their interaction with myeloma cells that leads to their apoptosis and the release of RANKL and sclerostin maintaining bone loss in these patients. This review focuses on the latest available data for the mechanisms of bone destruction in multiple myeloma.
溶骨性骨病是多发性骨髓瘤的常见并发症，可导致骨骼并发症，这是发病和死亡的重要原因。它是破骨细胞活性增加的结果，而成骨细胞并未随之进行反应性骨形成。最近的研究揭示了与破骨细胞激活和成骨细胞抑制有关的新分子和信号通路。其中，最重要的包括核因子-κB受体活化因子配体/骨保护素信号通路、巨噬细胞炎性蛋白以及激活素A，它们在骨髓瘤破骨细胞刺激中起关键作用，而无翅型（Wnt）信号抑制剂（硬化蛋白和Dickkopf-1）以及生长因子独立性-1被认为是骨髓瘤患者成骨细胞功能障碍的最重要因素。最后，成骨细胞作为正常骨重塑的关键细胞，其作用在过去几年中也通过与骨髓瘤细胞的相互作用得以揭示，这种相互作用导致成骨细胞凋亡，并释放核因子-κB受体活化因子配体（RANKL）和硬化蛋白，从而使这些患者持续出现骨质流失。本综述聚焦于多发性骨髓瘤骨破坏机制的最新可用数据。
