Indeed, by the strategies such as gene manipulation and genetic analysis, some factors critical for these pathways, such as FGF23 and Klotho in FGF signaling [51, 52], WNT3A and LRP5 in Wnt signaling [53, 54], IGF-1, IRS-1 and IRS-2 in IGF-1 signaling and downstream PI3K/AKT pathway [55–57], have been found to be relevant to osteoporosis. The gene discussed is IRS1; the disease is osteoporosis.