H&E and TRAP staining and micro-CT imaging showed that E-sEVs treatment dramatically prevented bone loss in the context of VPA-induced osteoporosis, but no difference was observed between sEVs group and E- sEVs group in OVX and glucocorticoid-induced osteoporotic mouse models, suggesting that E-sEVs might be a specific drug for VPA-induced bone loss with less side effects. Here, ACP5 is linked to osteoporosis.