Moran O, et al. - Whether osteoprotegerin (OPG) levels (a decoy receptor for receptor activator of nuclear factor κB ligand (RANKL), is known to inhibit RANK signaling) modify breast cancer risk through mammographic density, was investigated in premenopausal and postmenopausal women, presuming a possible association of RANKL pathway with mammographic density as the role of RANK signaling in mammary epithelial cell proliferation has already been established. Specifically observed in postmenopausal women, low OPG levels may be related to high mammographic density. For high-risk women with high mammographic density, particularly those with low circulating OPG levels, targeting RANK signaling may represent a plausible, non-surgical prevention option.