These results indicate that 15d-PGJ2 blocks breast cancer-mediated bone destruction by reducing the RANKL/OPG ratio in osteoblasts that are exposed to MDA-MB-231 cell-derived osteolytic factors and inhibiting the formation and function of osteoclasts in RANKL-treated osteoclast precursors in a PPAR-independent manner. This evidence concerns the gene TNFSF11 and breast cancer.