Bone-targeted agents in multiple myeloma

Osteolytic bone disease, characterizedby bone pain, increased risk of pathologicfractures, tumor-induced hypercalcemiaknown as skeletal-related events (SREs), isa frequent complication of patients withmultiple myeloma (MM) and persists evenin the absence of active disease, resulting ina major cause of morbidity and mortality.The interaction between myeloma cells andtheir surrounding cells in the bone marrow(BM) microenvironment promotes bothmyeloma cell growth and bone destructionand forms the vicious cycle of MM bonedisease. Therefore, therapeutic strategiestargeting the interaction between myelomacells and cellular components includingosteoclasts (OCs), stromal cells andosteoblasts (OBs) in the BM is crucial notonly to attain tumor regression but also toprevent or delay the incidence of SREs, which leads to improve survival and qualityof life in affected patients. Recently, severalnovel targets which act on components ofthe cycle for treating MM-associated bonedisease have been identified in addition tocurrent treatments including nitrogen-con-taining bisphosphonates. This review focus-es on the overview of pathophysiology inMM-associated bone disease and summa-rizes its current clinical management. Several novel bone-targeted agents in pre-clinical setting will be also discussed