This review article explores the role and applications of extracellular vesicles (EVs) in osteoporosis, a condition characterized by reduced bone mass and increased fracture risk. EVs, which are small membrane-bound structures released by various cells, play crucial roles in both pathological and physiological contexts. The article discusses the classification and biogenesis of EVs, their regulatory mechanisms in osteoporosis, and their potential as therapeutic modalities or biomarkers. **Key Points:** 1. **EV Biogenesis and Cargo:** - EVs are classified into exosomes (30-150 nm), microvesicles (100-1000 nm), and apoptotic bodies (1-5 μm). - Exosomes are formed through endosomal maturation and fusion with the cell membrane. - Microvesicles are formed by budding from the plasma membrane. - Apoptotic bodies are released from dying cells and contain degraded proteins and DNA. - EVs contain proteins, lipids, RNA, and DNA, with specific sorting mechanisms involving proteins like ESCRTs and RBPs. 2. **EVs in Osteoporosis:** - **Osteoclast-derived EVs (OC-EVs):** Promote bone resorption and inhibit bone formation. - **Osteoblast-derived EVs:** Influence bone formation and osteoclast activity. - **Mesenchymal Stem Cell-derived EVs (MSC-EVs):** Enhance osteoblast activity, inhibit osteoclast differentiation, and promote bone regeneration. - **Macrophage-derived EVs:** Influence osteogenic differentiation and bone metabolism. - **Endothelial Cell-derived EVs (EC-EVs):** Improve osteocyte activity and inhibit osteoclast ferroptosis. - **Muscle Cell-derived EVs:** Regulate bone homeostasis and osteoblast function. - **Tumor Cell-derived EVs:** Promote bone calcium loss and osteoporosis. 3. **Applications of EVs in Osteoporosis:** - **Diagnostic Tools:** EVs in body fluids can serve as biomarkers for osteoporosis, with specific miRNAs, proteins, and RNAs identified. - **Therapeutic Drugs and Engineered Optimization:** Natural EVs from various sources can be used as therapeutic agents, with engineering strategies to improve targeting and efficacy. - **Biomaterial-based EVs:** EVs can be loaded onto biomaterials like hydrogels and scaffolds for bone repair. 4. **Conclusion and Future Prospects:** - EVs are essential for understanding osteoporosis and its treatment. - Further research is needed to optimize EV-based therapies and understand their complex roles in bone homeostasis. This review highlights the multifaceted role of EVs in osteoporosis and their potential as therapeutic and diagnostic tools, emphasizing the need for further investigationThis review article explores the role and applications of extracellular vesicles (EVs) in osteoporosis, a condition characterized by reduced bone mass and increased fracture risk. EVs, which are small membrane-bound structures released by various cells, play crucial roles in both pathological and physiological contexts. The article discusses the classification and biogenesis of EVs, their regulatory mechanisms in osteoporosis, and their potential as therapeutic modalities or biomarkers. **Key Points:** 1. **EV Biogenesis and Cargo:** - EVs are classified into exosomes (30-150 nm), microvesicles (100-1000 nm), and apoptotic bodies (1-5 μm). - Exosomes are formed through endosomal maturation and fusion with the cell membrane. - Microvesicles are formed by budding from the plasma membrane. - Apoptotic bodies are released from dying cells and contain degraded proteins and DNA. - EVs contain proteins, lipids, RNA, and DNA, with specific sorting mechanisms involving proteins like ESCRTs and RBPs. 2. **EVs in Osteoporosis:** - **Osteoclast-derived EVs (OC-EVs):** Promote bone resorption and inhibit bone formation. - **Osteoblast-derived EVs:** Influence bone formation and osteoclast activity. - **Mesenchymal Stem Cell-derived EVs (MSC-EVs):** Enhance osteoblast activity, inhibit osteoclast differentiation, and promote bone regeneration. - **Macrophage-derived EVs:** Influence osteogenic differentiation and bone metabolism. - **Endothelial Cell-derived EVs (EC-EVs):** Improve osteocyte activity and inhibit osteoclast ferroptosis. - **Muscle Cell-derived EVs:** Regulate bone homeostasis and osteoblast function. - **Tumor Cell-derived EVs:** Promote bone calcium loss and osteoporosis. 3. **Applications of EVs in Osteoporosis:** - **Diagnostic Tools:** EVs in body fluids can serve as biomarkers for osteoporosis, with specific miRNAs, proteins, and RNAs identified. - **Therapeutic Drugs and Engineered Optimization:** Natural EVs from various sources can be used as therapeutic agents, with engineering strategies to improve targeting and efficacy. - **Biomaterial-based EVs:** EVs can be loaded onto biomaterials like hydrogels and scaffolds for bone repair. 4. **Conclusion and Future Prospects:** - EVs are essential for understanding osteoporosis and its treatment. - Further research is needed to optimize EV-based therapies and understand their complex roles in bone homeostasis. This review highlights the multifaceted role of EVs in osteoporosis and their potential as therapeutic and diagnostic tools, emphasizing the need for further investigation