Lungu Oxana, Toscani Denise, Giuliani Nicola
Laboratory of Hematology, Department of Medicine and Surgery, University of Parma, Parma, Italy.
Hematology and BMT Unit, "Azienda Ospedaliero-Universitaria di Parma", Parma, Italy.
J Bone Oncol. 2025 Mar 4;51:100668. doi: 10.1016/j.jbo.2025.100668. eCollection 2025 Apr.
Multiple myeloma (MM) is a hematological malignancy that leads to significant bone destruction, resulting in debilitating pain and skeletal-related events. The pathophysiology of osteolytic bone destruction in MM involves complex interactions between malignant plasma cells (PCs) and the bone marrow (BM) microenvironment. This review aims to provide a comprehensive synthesis of the cellular and molecular pathways underlying MM-associated bone disease. We discuss the role of osteoclast (OC), osteoblast (OB), osteocytes, along with the complex interactions between immune cells and the BM microenvironment in shaping disease progression. Additionally, we explore the molecular signaling pathways involved in bone disease as well as the influence of inflammatory cytokines, and the role of the metabolic alterations that characterize the MM BM. We also explore novel therapeutic strategies targeting these pathways to improve clinical outcomes. Understanding these mechanisms is crucial for the development of more effective treatments to prevent bone damage in MM patients.
多发性骨髓瘤（MM）是一种血液系统恶性肿瘤，会导致严重的骨质破坏，引发使人衰弱的疼痛和骨相关事件。MM中溶骨性骨破坏的病理生理学涉及恶性浆细胞（PC）与骨髓（BM）微环境之间的复杂相互作用。本综述旨在全面综合MM相关骨病背后的细胞和分子途径。我们讨论破骨细胞（OC）、成骨细胞（OB）、骨细胞的作用，以及免疫细胞与BM微环境之间在塑造疾病进展过程中的复杂相互作用。此外，我们探讨了参与骨病的分子信号通路以及炎性细胞因子的影响，以及MM骨髓特征性代谢改变的作用。我们还探索了针对这些途径的新型治疗策略以改善临床结局。了解这些机制对于开发更有效的治疗方法以预防MM患者的骨损伤至关重要。
