Tumor-derived factors, such as PTHrP, Dickkopf-1 (DKK-1), IL-8, TNF, TGF-β, and HPSE, can activate osteoclast maturation and promote bone resorption by receptor activator for NF-κB ligand (RANKL)-dependent and RANKL-independent mechanisms. The gene discussed is TNFSF11; the disease is neoplasm.