Myeloma and osteoclast relationship

Multiple myeloma (MM) is a plasma cell malignancy characterized by the high capacity to induce bone destruction. Osteolysis is the hallmark of bone lesions in MM patients due to a severe uncoupled and unbalanced bone remodeling with an increase of osteoclast (OC) formation and activity and the suppression of osteoblast formation and function. The biological mechanisms involved in MM-induced osteoclastogenesis have been elucidated in recent years, highlighting the critical role of the RANKL system. The activation of OCs by MM cells in turn stimulates MM cell survival and growth of MM cells. In vivo models also support the pro-survival critical role of OCs in MM patients. In this chapter we summarize the pathophysiological mechanisms involved in MM-induced activation of the OC formation and activity focusing on the reciprocal relationship between OCs and MM cells.