Rong Cai,1,* Yuanyuan Jiang,1,* Haiyan Sun,2,* Fengyi Du,3 Like Zhu,1 Jialing Tao,1 Long Xiao,1,* Zhirong Wang,1 Haiwei Shi1 

1Translational Medical Innovation Center, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, People’s Republic of China; 2Department of Anesthesiology, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, People’s Republic of China; 3Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, Jiangsu, 212013, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Zhirong Wang, Translational Medical Innovation Center, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, People’s Republic of China, Email zjgfy_spine_wzr@njucm.edu.cn Haiwei Shi, Translational Medical Innovation Center, Zhangjiagang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, 215600, People’s Republic of China, Email zjgzy059@njucm.edu.cn

Abstract: Osteoporosis (OP) represents a significant global health burden, characterized by reduced bone density and an increased risk of fractures due to imbalances in bone remodeling processes. Traditional therapeutic strategies, while mitigating symptoms, often lack the precision to address the multifactorial nature of OP effectively. In recent years, functionalized nanoparticles have emerged as a versatile platform, offering enhanced drug delivery, targeted therapy, and the potential for theranostic applications in OP treatment. This review examines the various types and architectures of functionalized nanoparticles, emphasizing their unique capabilities in targeting bone tissue and modulating bone metabolism. By focusing on their roles in inflammation modulation, oxidative stress reduction, and promoting bone regeneration, we discuss the mechanisms by which these nanoparticles offer multifunctional, synergistic effects. Additionally, we address the challenges in achieving controlled drug release, biocompatibility, and effective bone tissue penetration, proposing future directions that integrate emerging nanotechnologies, biomechanics, and regenerative medicine approaches to optimize therapeutic outcomes. This comprehensive review provides a foundation for the future development of functionalized nanoparticle therapies, positioning them as promising tools for advanced, personalized OP treatment.

Keywords: functionalized nanoparticles, osteoporosis, bone tissue targeting, drug delivery