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Eventually, we verified the bone targeting ability, therapeutic efficiency, and biocompatibility of the novel bone target iron oxides in ovariectomy-induced osteoporotic mice. Besides, alendronate, a clinically used anti-osteoporosis bisphosphate, was employed to precisely deliver the IONPs to the bone tissues and played a synergically therapeutic role. Meanwhile, IONPs promoted the osteogenic differentiation of bone marrow mesenchymal stem cells and inhibited the osteoclast differentiation of monocytes from IONPs treated mice. In this study, we further demonstrated that daily administration of IONPs relieved estrogen deficiency-induced osteoporosis via scavenging reactive oxygen species in vivo. Our previous work demonstrated that iron oxide nanoparticles (IONPs) could positively regulate bone metabolism in vitro. scattering (DLS) instrument using a 90 Plus-8particle size analyzer (Malvern, Zetasizer Nano ZS90).intensitiesBriefly, 200 µL of M-dots based samples were firstly passed through a 0.22 µm filter and then were filled with a 200standardµL clean microcuvette for DLS analysis. Recently, the therapeutic methods for osteoporosis have shifted towards the regulation of local immunity in bone tissues, which could provide a suitable environment for the positive regulation of bone metabolism, promoting osteogenic differentiation and inhibiting osteoclast differentiation. Osteoporosis is the most common degenerative orthopedic disease in the elderly. Here, we have used zeta analyzer (Malvern Zetasizer Nano ZS90, the Netherlands) to measure the distribution of nanoparticles in the aqueous solution. Malvern Instruments Limited Printed in England MRK1378-01 Enigma Business Park Grovewood Road, Malvern Worcs, WR14 1XZ, U.K.