LAUSR

Abstract Osteoporosis (OP), which is associated with an imbalance between osteoblasts (OBs) and osteoclasts (OCs), is sequentially treated with anabolic and anti-resorption agents in the clinic to improve outcome. However, the long duration of treatment and the accuracy of dosing are still major limiting factors affecting outcome. In the present study, a radial extracorporeal shock wave (rESW) responsive precise sequential release nanoplatform with zoledronic acid (ZOL) adsorbed onto the surface of hollow hydroxyapatite nanoparticles (hNPs) is reported. The ZOL on the surface of hNPs was rapidly released and inhibited hyperactivation of OCs in the OP region. The remaining hNPs with a wall thickness of approximately 10 nm were crushed into fragments by rESW to control Ca2+ release and proton neutralization, promoting anabolic metabolism. In addition, mechanical stimulation by rESW helped bone formation. In vivo, maximum anti-resorption and pro-anabolic effects, marked improvements in bone-associated parameters and mechanical properties in ovariectomy-induced OP rats were achieved following co-treatment with rESW and ZOL-hNPs. These findings suggest that this precise sequential release nanoplatform based on rESW can be used for effective anti-OP treatment.