Macrophages with upregulated RANKL (Receptor Activator of Nuclear Factor Kappa-B ligand) in their cell surface, in GCTB’s tumor microenvironment, secrete MCSF (Macrophage Colony Stimulation Factor) and display an extensive combination of receptors with low OPG secretion, which in turn produce a large number of large osteoclastic giant cells responsible for osteoclastogenesis in GCTB (Figure 3) [134,135]. The gene discussed is TNFSF11; the disease is neoplasm.