Dual-Action ascorbic acid–maghemite hybrid nanoparticles enhance osteoblast activity and suppress osteoclast activity in osteoporosis

Osteoporosis is a progressive skeletal disorder involving decreased bone density and compromised structural integrity, ultimately heightening fracture risk. While maghemite nanoparticles enhance osteoblast activity, their limited influence on osteoclasts reduces their therapeutic efficacy. To overcome this, we developed ascorbic acid-coated maghemite nanoparticles (AMN) that were further surface-modified with hyaluronic acid and polyethylene glycol for improved biocompatibility and stability. AMN scavenges reactive oxygen species and promotes collagen synthesis, offering a dual-functional approach to bone regeneration. Physicochemical analyses, including zeta potential, UV–Vis spectroscopy, and SEM, confirmed AMN formation and stability. In vitro , AMN significantly enhanced MG-63 cell growth, collagen synthesis, ALP activity, and mineral formation. It also TRAP activity measured during osteoclast induction from RAW 264.7 cell, demonstrating its osteoclast-inhibitory potential. Furthermore, AMN supports the formation of a collagen-rich extracellular matrix, facilitating biomineralization and osteogenesis. In vivo , ovariectomized rats treated with AMN exhibited increased bone volume fraction, thicker trabeculae, and reduced trabecular separation, indicating enhanced osteogenesis (BMP2, RUNX2, COL1, and osteocalcin) and suppressed bone resorption (TRAP, RANKL, and RANK). AMN is a promising therapeutic candidate for osteoporosis as it simultaneously promotes bone formation and inhibits bone loss, with strong potential for clinical applications.