fluorescence imaging revealed that S-Z@ALN-SPIONs-EXO achieved rapid and pronounced bone accumulation within 12 h post-injection, attributable to the synergistic actions of ALN-mediated bone targeting and SPION-facilitated magnetic retention. In the OVX osteoporotic mouse model, micro-CT and histological analyses confirmed substantial restoration of trabecular microarchitecture, increased collagen deposition, and marked inhibition of osteoclastogenesis, without detectable toxicity in major organs. This dual-targeted strategy outperformed single-modification systems, demonstrating its potential as an effective platform for osteoporosis therapy.