Activated AKT suppress MDM2 by phosphorylation, which results in the release p53 from negative control of phosphorylated MDM2.52, 53, 54 Following, activated p53 ultimately lead to progressive inflammation, premature atrophy and cell death.52, 53, 54, 55 The recent study has demonstrated that PI3K‐AKT inhibitor as well as MDM2 antagonist regulated tumour cells apoptosis, which showed significant anti‐cancer effect.56 However, the effect of PI3K‐AKT‐induced cell death has not been reported in osteoporosis. This evidence concerns the gene MDM2 and osteoporosis.