The RANKL serum concentration was higher in thyroid cancer patients with BM than in those without metastasis or with lung metastasis alone, and the outcomes that metformin inhibited ATC tumor growth in BM by inhibiting osteoblastic RANKL production and osteoclast differentiation indicated BM of thyroid cancer were at least partly mediated by increasing the level of RANKL in osteoblasts followed by activating osteoclast differentiation and causing bone resorption (84). This evidence concerns the gene TNFSF11 and neoplasm.