Bone-modifying therapy in multiple myeloma: a comprehensive review

Area of Science:

• Hematologic Malignancies
• Bone Biology
• Pharmacology

Background:

• Multiple myeloma (MM) involves plasma cell proliferation in bone marrow.
• Skeletal-related events (SREs), characterized by osteolytic bone lesions, are a common and severe complication of MM.
• MM disrupts bone homeostasis through various pathways and cytokines, leading to significant morbidity.

Purpose of the Study:

• To review the pathogenesis of SREs in multiple myeloma.
• To provide an overview of evidence-based, guideline-recommended treatments for SREs.
• To identify unmet needs in the management of MM-related bone disease.

Main Methods:

• Literature review of pathogenesis and treatment of SREs in MM.
• Analysis of historical and current therapeutic strategies, including bisphosphonates and denosumab.
• Discussion of emerging research and future directions in precision medicine for MM bone complications.

Main Results:

• MM-induced bone lesions result from altered bone homeostasis.
• Bisphosphonates were historically used but have limitations; denosumab is a viable alternative, though it has adverse events.
• Anti-MM therapies may influence bone turnover, but data are preliminary.

Conclusions:

• SREs are a major challenge in multiple myeloma management.
• Current treatments like denosumab offer benefits but have drawbacks, and adverse events require attention.
• There is a significant unmet need for advanced translational research and clinical trials to develop precision, risk-adapted therapies for MM bone disease.