Abstract：Objective：To explore the correlation between PI3K / Akt signaling pathway and osteosarcopenia(OS) based on bioinformatics and animal experiments. Methods：The disease-related database was searched to screen OS targets，the OS target protein interaction network was constructed，the core targets were screened，and GO and KEGG were enriched and analyzed. Six months old female SPF SD rats were randomly divided into Control group，Sham group，Sham+DXM group， OVX group and OVX + DXM group，with 8 rats in each group. Rats in Sham group and Sham + DXM group underwent sham operation，and rats in OVX group and OVX+DXM group underwent bilateral oophorectomy. One week after operation，rats in Sham+DXM group and OVX+DXM group were injected intraperitoneally for 2 weeks. Three months after modeling，the rats in each group were tested for forelimb grip，whole body and femoral bone mineral density，and the expression of PI3K and Akt protein in femur and gastrocnemius muscle. Results：130 OS related targets were screened by bioinformatics. OS core target screening and KEGG pathway enrichment analysis predicted that PI3K/Akt signaling pathway might be involved in the pathogenesis of OS. Animal experiments showed that compared with the Control group and the Sham group，the forelimb grasping force， whole- body bone mineral density and femoral bone mineral density in the OVX + DXM group decreased significantly， and the expression of PI3K and Akt protein in femur and gastrocnemius muscle decreased significantly. Conclusion： The inhibition of PI3K/Akt signaling pathway is closely related to the pathogenesis of OS， which provides an intervention target for the development of OS drugs and a research example for the study of the pathological mechanism of new diseases.