In the vicious cycle model, tumor cells will stimulate an exaggerated formation and activation of osteoclasts by directly or indirectly facilitating the local production of cytokines and growth factors, including interleukin (IL)-1, IL-6, IL-8, IL-11, prostaglanding E3, tumor necrosis factor alpha (TNF-α), M-CSF, vascular endothelial growth factor (VEGF), and RANKL [44,46,47,48,49,50,51,52,53,54,55]. The gene discussed is TNFSF11; the disease is neoplasm.