Peng Yin,1,2,* Shilin Dong,1– 3,* Jiaoyang Yu,1,2,* Zhengnan Zhao,1– 3 Yunxiang Hu1,2 

1Department of Orthopaedic Trauma, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 2School of Graduates, Dalian Medical University, Dalian, Liaoning, People’s Republic of China; 3Department of Hand and Foot Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Zhengnan Zhao, Department of Hand and Foot Surgery, The Second Affiliated Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, Liaoning, 116027, People’s Republic of China, Email zhengnanbx@163.com Yunxiang Hu, Department of Orthopaedic Trauma, The Second Affiliated Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, Liaoning, 116027, People’s Republic of China, Email hooshawnzee@dmu.edu.cn

Abstract: Osteoporosis (OP) is a degenerative bone disease characterized by decreased bone mass and deterioration of bone tissue microstructure, which increases skeletal fragility and the risk of fractures. Currently, the drugs used clinically to treat OP are primarily classified into two types: bone resorption inhibitors and bone formation promoters. Although they demonstrate certain efficacy, most anti-OP medications do not specifically target bone tissue and may produce significant side effects. In recent years, bone-targeted therapies nano-drug delivery systems (NDDSs) for OP have gained attention due to their high drug loading capacity, strong targeting ability, ease of modification, and good biocompatibility. These characteristics effectively address the limitations of traditional therapies and have been widely applied in the treatment of OP. Therefore, this article systematically summarizes recent applications of NDDSs (including inorganic, organic, biogenic, and hybrid systems) in the treatment of OP, focusing on targeting design strategies, in vitro and in vivo efficacy validation, and clinical translation challenges, aiming to provide theoretical references for the development of the next generation of targeted nanomedicines.

Keywords: osteoporosis, nano-drug delivery systems, nanoparticles, nanomaterials, targeted therapy