Bone-targeted agents in multiple myeloma

Osteolytic bone disease, characterized by bone pain, increased risk of pathologic fractures, tumor-induced hypercalcemia known as skeletal-related events (SREs), is a frequent complication of patients with multiple myeloma (MM) and persists even in the absence of active disease, resulting in a major cause of morbidity and mortality. The interaction between myeloma cells and their surrounding cells in the bone marrow (BM) microenvironment promotes both myeloma cell growth and bone destruction and forms the vicious cycle of MM bone disease. Therefore, therapeutic strategies targeting the interaction between myeloma cells and cellular components including osteoclasts (OCs), stromal cells and osteoblasts (OBs) in the BM is crucial not only to attain tumor regression but also to prevent or delay the incidence of SREs, which leads to improve survival and quality of life in affected patients. Recently, several novel targets which act on components of the cycle for treating MM-associated bone disease have been identified in addition to current treatments including nitrogen-containing bisphosphonates. This review focuses on the overview of pathophysiology in MM-associated bone disease and summarizes its current clinical management. Several novel bone-targeted agents in preclinical setting will be also discussed.