VnP-16 is a peptide corresponding to residues 270-281 of human vitronectin, which exerts an anti-osteoporotic effect via beta1 and alphavbeta3 integrin signaling. VnP-16 promotes bone formation by accelerating osteoblast differentiation through direct interaction with beta1 integrin followed by FAK activation, while inhibiting bone resorption through restraint of JNK-c-Fos-NFATc1 induced osteoclast differentiation and alphavbeta3 integrin-c-Src-PYK2 mediated resorption. In a mouse model of estrogen deficiency induced osteoporosis, VnP-16 reverses ovariectomy induced bone loss by increasing osteoblast differentiation and promoting bone formation, while decreasing osteoclastogenesis and inhibiting bone resorption.