Mechanisms of Altered Bone Remodeling in Multiple Myeloma

Multiple myeloma (MM) is a hematologic malignancy of plasma cells proliferating in the bone marrow and it is associated with the osteolytic bone disease. About 70% of myeloma patients show the bone disease at diagnosis and 15-20% have pathologic fractures. The osteolytic disease is due to the altered bone remodeling with increased activity of osteoclasts, the bone resorbing cells, and the reduced activity of osteoblasts, the bone forming cells. In the bone marrow microenvironment, the deregulated activity of bone cells is due to the malignant plasma cells through the release of soluble molecules or cell-cell contact. Recently, the key role of osteocytes, the orchestrators of bone remodeling, and the adipocytes has been highlighted in MM-bone disease. In this review, we overview the mechanisms leading to increased bone resorption as well as suppressed osteoblast formation and activity in MM-bone disease, thus highlighting cytokines that will represent new therapeutic targets to improve bone health in MM-bone disease.