Metformin activates the AMPK pathway to promote osteoblast differentiation.[22] In recent years, with the progress of biological science, more and more basic studies based on mice have explained the mechanism of metformin effect on osteoporosis at the molecular level: metformin inhibits E2F1-mediated autophagy of osteoclast precursors to reduce bone loss, metformin reverses oxidative stress-induced apoptosis of osteoblast precursor cells through the EGFR/GSK-3β/calcium pathway to preserve more osteoblasts and protects the differentiation potential of osteoblasts in high glucose environment. Here, E2F1 is linked to osteoporosis.