Model for MM-induced osteoclastogenesis through RANKL induction.

Myeloma cells induce an imbalance in the OPG/RANKL ratio in stromal/osteoblastic cells through the cell-to-cell contact. In addition, myeloma cells stimulate RANKL and down-regulate IFN-γ secretion by T cells at least in part through the direct release of IL-7 or indirect involvement of the high IL-6 levels induced by myeloma cells in the bone environment. The high BM expression and level of the critical osteoclastogenetic factor RANKL associated with lower levels of osteoclastogenetic inhibitors, such as OPG and IFN-γ, may be involved in MM-induced activation of osteoclasts.