In the present study, we revealed that SA can bind to RANKL and its receptor RANK and disrupt the RANKL–RANK interaction and that, via inhibition of RANKL‐stimulated RANK–TRAF6 binding and RANK signalling pathways activation, it effectively suppresses RANKL‐induced osteoclastogenesis in vitro and protects against osteoporosis in vivo. This evidence concerns the gene TNFRSF11A and osteoporosis.