Exosome-Based Regulation and Therapy in Osteoporosis: Mechanistic Insights and Translational Advances

Abstract: Osteoporosis is a chronic and progressive skeletal disease characterized by decreased bone mass and microarchitectural deterioration, leading to increased fracture susceptibility. Emerging evidence suggests that extracellular vesicles, particularly exosomes, play a pivotal role as mediators of intercellular communication within the bone microenvironment. This review focuses on the functional roles of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) and other bone-resident cells in modulating bone remodeling. We detail the mechanisms by which exosome-encapsulated non-coding RNAs influence osteoblast and osteoclast activity through key regulatory pathways. Furthermore, we examine how pathological conditions, such as chronic inflammation and diabetes, reshape exosomal cargo, contributing to dysregulated bone homeostasis through mechanisms involving ferroptosis and oxidative stress. Advances in therapeutic applications are discussed, including engineered exosomes, bone-targeting delivery strategies, and hydrogelbased scaffolds. We also highlight the diagnostic potential of exosome-derived RNAs as biomarkers for disease progression and treatment response. Although exosomebased approaches represent a promising frontier in osteoporosis therapy and diagnosis, challenges, such as cargo heterogeneity, targeting specificity, and scalable manufacturing, remain to be addressed before clinical implementation.