Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan.
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
Int J Mol Sci. 2022 Mar 14;23(6):3112. doi: 10.3390/ijms23063112.
Multiple myeloma is a hematologic malignancy of plasma cells that causes bone-destructive lesions and associated skeletal-related events (SREs). The pathogenesis of myeloma-related bone disease (MBD) is the imbalance of the bone-remodeling process, which results from osteoclast activation, osteoblast suppression, and the immunosuppressed bone marrow microenvironment. Many important signaling cascades, including the RANKL/RANK/OPG axis, Notch signaling, the Wnt/β-Catenin signaling pathways, and signaling molecules, such as DKK-1, sclerostin, osteopontin, activin A, chemokines, and interleukins are involved and play critical roles in MBD. Currently, bisphosphonate and denosumab are the gold standard for MBD prevention and treatment. As the molecular mechanisms of MBD become increasingly well understood, novel agents are being thoroughly explored in both preclinical and clinical settings. Herein, we will provide an updated overview of the pathogenesis of MBD, summarize the clinical management and guidelines, and discuss novel bone-modifying therapies for further management of MBD.
多发性骨髓瘤是一种浆细胞的血液系统恶性肿瘤，可导致骨质破坏病变和相关的骨骼相关事件（SREs）。骨髓瘤相关骨病（MBD）的发病机制是骨重塑过程的失衡，这是由于破骨细胞激活、成骨细胞抑制和免疫抑制的骨髓微环境所致。许多重要的信号级联反应，包括 RANKL/RANK/OPG 轴、Notch 信号通路、Wnt/β-连环蛋白信号通路以及信号分子，如 DKK-1、骨硬化蛋白、骨桥蛋白、激活素 A、趋化因子和白细胞介素等，都参与其中并在 MBD 中发挥关键作用。目前，双磷酸盐和地舒单抗是 MBD 预防和治疗的金标准。随着对 MBD 分子机制的了解越来越深入，新的药物正在临床前和临床环境中得到深入探索。本文将提供 MBD 发病机制的最新概述，总结临床管理和指南，并讨论新的骨修饰疗法以进一步管理 MBD。
