Multiple myeloma (MM) is a plasma cell malignancy characterized by a tight relationship with the bone microenvironment cells. MM cells induce a significant alteration of the bone remodelling process due to the increase of osteoclast formation and activation and to the suppression of osteoblast differentiation leading to the impairment of bone formation and the development of osteolytic lesions. Recently, an increase of osteocyte death has been also demonstrated in MM patients suggesting a potential role of these cells in the alterations of bone remodelling in MM. Interestingly, the increased osteoclastogenesis and the impaired bone formation in turn support myeloma cell proliferation and survival in vitro and promote tumoral progression in vivo. In addition it has been reported that quiescent myeloma cells with stem cell features may reside in the hypoxic osteoblastic niche for protection from apoptotic stimuli and are involved in the drug resistance and the relapse of the disease.
Several studies have investigated the mechanisms involved in the relationship between myeloma cells and bone microenvironment cells. MM cells are able to stimulate the osteoclastogenesis and to suppress osteoblast formation and viability either through the release of soluble factors or the cell-to-cell contact. Recently the potential role of miRNAs has been also suggested in the mechanisms involved in the suppression of osteoblast differentiation in MM. The identification of potential pathways involved in the relationship between bone and myeloma cells has leaded to identify new therapeutic targets including RANKL, activin-A, sclerostin, HIF1α, and Wnt signaling pathways. Several new drugs have been developed and are under investigation for their future use in MM patients.