More importantly, we blocked the biological functions of ESR1 with MPP, and the results showed that the inhibitory effects of ICT on osteoclast differentiation and anti-osteoporosis were significantly attenuated, especially in trabecular BV and BMD (Figures 6A–H), while the levels of TRAP and RANKL were significantly increased, and the level of OPG was significantly decreased (Figures 6I–K). This evidence concerns the gene TNFRSF11B and osteoporosis.