During the increased osteolysis, tumor growth-promoting factors are released from the bone matrix (e.g., bone morphogenetic proteins (BMPs), insulin-like growth factor 1 (IGF-1), and transforming growth factor-beta1 (TGF-β1)), resulting in a feedforward loop referred to as the vicious cycle of bone metastasis [21,22]. The gene discussed is IGF1; the disease is neoplasm.