Immunomodulation of multiple myeloma bone disease

Multiple myeloma (MM) is a clonal malignancy of terminally differentiated plasma cells. Myeloma patients often have extensive skeletal complications, including bone pain, osteolytic lesions and pathological fractures, which represent the major cause of morbidity and possible mortality. Osteolysis is due to the uncoupling of bone cell activity, caused by osteoclast activation and osteoblast inhibition. Osteoclast biology is dominantly regulated by the RANK/RANKL/OPG axis. A disruption of RANKL/OPG ratio, due to the prevalence of RANKL and/or inactivation of OPG, has been reported in MM bone disease by different mechanisms involving either malignant plasma cells and/or other cells of immune system. Despite the major involvement of RANKL in MM is well documented, a dysregulated production of other cytokines either with pro- or anti-osteoclastogenic activity can also contribute to the development of osteolytic lesions by acting directly on bone cells or altering RANKL/OPG axis. This review focuses on molecules produced by cells of immune system able to induce bone destruction in MM bone disease.