Biological relationship between bone and myeloma cells

Multiple myeloma is a B cell neoplasm caused by the monoclonal expansion and infiltration of malignant plasma cells in the bone marrow. Myeloma growth can significantly disrupt normal bone function by cell-to-cell interactions and by the secretion of factors that promote osteoclastic bone resorption and inhibit osteoblastic bone formation. This imbalance can lead to the development of osteolytic lesions, hypercalcemia, and susceptibility to bone fractures. Ultimately a vicious cycle is created that increases bone damage, releasing more factors that in turn enhance myeloma cell growth. In addition, other cells within the bone marrow microenvironment, including osteocytes, adipocytes, and immune cells, can influence myeloma cell colonization, survival, and subsequent growth or dormancy. Myeloma in vivo models, patient studies, and clinical trials support these findings. In this chapter we will discuss the biological relationship between cells in the bone marrow microenvironment and myeloma cells, describing key mechanisms that disrupt normal bone function and current bone modulating therapies.