Similarly, high levels of RANKL present at a skeletal level - especially in the context of metastatic bone disease [44] - may explain why OPG protects bone microenvironment from breast cancer-induced osteolysis and mitigates intra-osseous tumor growth, whereas it is able to promote primary tumor growth and cancer cells spread to sites out of the bone [134]. Here, TNFRSF11B is linked to breast cancer.