Therapeutic strategy for exosome-based bone regeneration to osteoporosis: Challenges and potential solutions

Background: Osteoporosis (OP) is a progressive bone disease marked by reduced bone mass and microarchitectural deterioration, thereby increasing fracture risk. Current therapies only partly restore bone quality and often cause side effects with long-term use. Recent studies highlight exosomes, a subtype of extracellular vesicles, as key regulators of bone remodeling with promising regenerative potential. However, their role in osteoporosis remains underexplored. Aim of review: This review aims to investigate how the established role of exosomes in bone regeneration may inform novel therapeutic strategies for osteoporosis. By linking general bone repair mechanisms with osteoporotic pathology, it evaluates the translational potential and limitations of exosome-based interventions. Key scientific concepts of review: Exosomes derived from mesenchymal stem cells, osteoblasts, osteoclasts, and macrophages regulate bone homeostasis by modulating osteogenesis, osteoclastogenesis, and immune responses. Their regenerative effects in non-osteoporotic settings are well documented. However, challenges such as exosome heterogeneity, rapid clearance, and poor targeting efficiency impede their direct application in osteoporosis. Recent bioengineering approaches, including osteogenic RNA or protein loading and surface modifications for bone targeting, show promise. Moreover, combining exosomes with immunomodulatory or synergistic therapies may further enhance their efficacy. Despite these advances, gaps persist in standardizing isolation techniques, ensuring batch consistency, and scaling up production for clinical use. This review consolidates current knowledge and outlines directions for adapting exosome-based bone regenerative strategies to osteoporosis treatment.