Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives

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...

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Main Authors: Oxana Lungu, Denise Toscani, Nicola Giuliani
Format: Article
Language:English
Published: Elsevier 2025-04-01
Series:Journal of Bone Oncology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2212137425000090
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author Oxana Lungu
Denise Toscani
Nicola Giuliani
author_facet Oxana Lungu
Denise Toscani
Nicola Giuliani
author_sort Oxana Lungu
collection DOAJ
description 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.
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spelling doaj-art-176de6c246e0464f94850854a3d8f2fc2025-08-20T02:50:53ZengElsevierJournal of Bone Oncology2212-13742025-04-015110066810.1016/j.jbo.2025.100668Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectivesOxana Lungu0Denise Toscani1Nicola Giuliani2Laboratory of Hematology, Department of Medicine and Surgery, University of Parma, Parma, ItalyLaboratory of Hematology, Department of Medicine and Surgery, University of Parma, Parma, ItalyLaboratory of Hematology, Department of Medicine and Surgery, University of Parma, Parma, Italy; Hematology and BMT Unit, “Azienda Ospedaliero-Universitaria di Parma”, Parma, Italy; Corresponding author at: Dept. of Medicine and Surgery, University of Parma, Via Gramsci 14, 43126 Parma, Italy.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.http://www.sciencedirect.com/science/article/pii/S2212137425000090Multiple myelomaBone diseaseOsteoblastsOsteoclastsOsteocytesMolecular pathways
spellingShingle Oxana Lungu
Denise Toscani
Nicola Giuliani
Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives
Journal of Bone Oncology
Multiple myeloma
Bone disease
Osteoblasts
Osteoclasts
Osteocytes
Molecular pathways
title Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives
title_full Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives
title_fullStr Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives
title_full_unstemmed Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives
title_short Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives
title_sort mechanistic insights into bone destruction in multiple myeloma cellular and molecular perspectives
topic Multiple myeloma
Bone disease
Osteoblasts
Osteoclasts
Osteocytes
Molecular pathways
url http://www.sciencedirect.com/science/article/pii/S2212137425000090
work_keys_str_mv AT oxanalungu mechanisticinsightsintobonedestructioninmultiplemyelomacellularandmolecularperspectives
AT denisetoscani mechanisticinsightsintobonedestructioninmultiplemyelomacellularandmolecularperspectives
AT nicolagiuliani mechanisticinsightsintobonedestructioninmultiplemyelomacellularandmolecularperspectives