IGF1 and neoplasm: Key mediators of the osteolytic tumor pathway include the parathyroid hormone-related peptide (PTHrP), which upregulates RANK-L from osteoblasts and stromal cells, resulting in down regulation of osteoprotegerin, activation of osteoclasts, production of TGF-β and IGF which in turn promotes tumor cell growth and further release of PTHrP, creating a “vicious cycle of bone metastases” [18] (Figure 1).