Enhancing osteoporosis treatment: emerging roles of engineered exosomes in bone regeneration and repair

Osteoporosis, a prevalent metabolic bone disease, is characterized by reduced bone density and an increased risk of fractures. The primary challenge in treating osteoporosis lies in correcting the imbalance between bone resorption and formation while minimizing the associated risks of treatment. Current drugs, such as bisphosphonates, teriparatide, and romosozumab, help reduce fracture risk but have limitations, including long-term safety concerns, incomplete protection, and poor patient adherence. Exosomes, small extracellular vesicles with natural biocompatibility and low immunogenicity, have emerged as promising therapeutic candidates for osteoporosis. These vesicles carry bioactive molecules that regulate bone remodeling, promote osteogenesis, and inhibit osteoclastogenesis. Advances in bioengineering have improved the targeting efficiency and drug-loading capacity of exosomes, while their combination with biomaterials supports localized and sustained bone regeneration. The review explores the signaling mechanisms that contribute to osteoporosis and highlights the biological functions of exosomes. Furthermore, it addresses the challenges in translating exosome-based therapies, such as variability in exosome content, production standardization, scalability, and unresolved safety concerns. Preclinical models play a key role in assessing therapeutic efficacy. The review also considers interdisciplinary innovations, including nanotechnology, biomaterials, advanced imaging, and artificial intelligence, and their potential to enhance the translation of exosome therapies. Exosome therapies represent a promising next-generation strategy for the treatment of osteoporosis. With continued advancements in engineering, clinical evaluation, and interdisciplinary innovations, exosomes could offer safer, more effective, and personalized treatment options for osteoporosis. However, challenges remain in ensuring the consistency, safety, and scalability of exosome production, which must be addressed before widespread clinical adoption.