Abstract
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.
Highlights
Multiple myeloma (MM), known as plasma cell myeloma, is the second-most common hematological malignancy and is characterized by the malignant proliferation of monoclonal plasma cells in the bone marrow, leading to bone destruction, marrow failure, and associated end organ damage [1]
We discussed the pathogenesis of myeloma-related bone disease, the current treatment and the novel agents in development for the treatment of MBD
The complexity of cross relationships between MM cells and the surrounding cells has a critical role in MBD
Summary
Multiple myeloma (MM), known as plasma cell myeloma, is the second-most common hematological malignancy and is characterized by the malignant proliferation of monoclonal plasma cells in the bone marrow, leading to bone destruction, marrow failure, and associated end organ damage (hypercalcemia, renal insufficiency, anemia, or bone lesions) [1]. According to statistics for the United States, MM accounts for about 1.8% of all cancers and 18% of hematologic malignancies. MM is most frequently diagnosed in people aged 65 to 74 years; the median age is 69 years [2]. The incidence of MM is increasing worldwide, but the rate of increase is greatest in Asia. In Taiwan, the age-adjusted incidence of MM increased by 13% between 2007 and 2012 [3].
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