Bone-modifying therapy in multiple myeloma: a comprehensive review

Multiple myeloma (MM) is a clonal hematologic malignancy characterized by plasma cell proliferation in the bone marrow. One of the most common clinical presentations is skeletal-related events (SREs), characterized by osteolysis of the bone, leading to a significant morbidity and mortality. The main aim of this review article is to provide an overview of the pathogenesis and evidence-based, guideline-recommended treatment of SREs. MM bone homeostasis is altered by numerous pathways and cytokines, leading to the pathogenesis of bone and osteolytic lesions. Historically, bisphosphonates were the mainstay of treatment, but due to toxicities and contraindications in renal impairment, denosumab-a monoclonal antibody targeting the RANKL-RANK axis, given once per month-may have become the treatment of choice, especially with three biosimilars being approved, yet adverse events may be troublesome. Furthermore, it seems that anti-MM-directed therapy has an impact on bone turnover, yet the results are premature. However, despite basic research unraveling novel targets such as micro ribonucleic acids, translational research and randomized clinical trials are lagging behind, making this area an unmet need-despite the fact that precision, risk-adapted, biomarker- and imaging-driven medicine should be a valid clinical goal in this setting.