The "vicious cycle" of osteolytic bone metastasis

When cancer cells metastasize to bone, bone resorption is increased by osteoclast activating factors produced by the tumor cells. These osteoclast activating factors include PTHrP, IL-6, and M-CSF, which increase osteoclast formation. In addition, tumor cells induce cells in the bone environment, such as marrow stromal cells and osteocytes, to produce RANKL and decrease production of OPG and adipocytes to produce inflammatory cytokines that can increase osteoclast formation and enhance tumor growth. The increased bone resorption releases growth factors from the bone matrix that in turn increase tumor growth. This creates a "vicious cycle" of tumor cells increasing bone resorption that in turn increases tumor growth in bone.