In the present study, we sought to understand whether the up-regulation of SIRT1 induced by 17β-E2 could promote autophagy via the AMPK-mTOR signaling pathway and inhibit apoptosis via the FOXO3a activation in osteoblasts, and SIRT1 might become a more significant target in osteoporosis treatment. Here, SIRT1 is linked to osteoporosis.