Consistent with the abovementioned hypothesis, we observed that the numbers of TRAP+-multinucleated mature osteoclasts and TRAP enzymatic activity were drastically increased in pre-osteoclasts (pre-OC) treated with conditioned media (CM) from BC/circIKBKB cells (CM-BC/circIKBKB) (Fig. 2c). This evidence concerns the gene ACP5 and breast cancer.