These ROS stimulate osteoclast differentiation and bone resorption in murine calvarial and bone marrow cultures as well as in osteoblasts/spleen cells cocultures by the stimulation of the osteoclastogenic nuclear factor-kappa β ligand (RANKL)–RANK signaling pathway.[19] Binding of RANKL to RANK initiates osteoclast differentiation/activation, and thus is critical for their survival and promotion of bone resorption, and ultimately plays a role in pathogenesis of postmenopausal osteoporosis.[20,21]. This evidence concerns the gene TNFRSF11A and postmenopausal osteoporosis.