The ratio of RANKL/OPG is much higher in Ctsk‐Cre;Trp53f/f/Rb1f/f mice compared to that in the control, suggesting that osteoblasts/osteocytes derived from Ctsk+ cells with loss of Trp53 and Rb1 may promote osteoclastogenesis and osteolysis in tumor microenvironment through increasing RANKL expression. This evidence concerns the gene TNFRSF11B and neoplasm.