Harnessing extracellular vesicles as an emerging diagnostic and therapeutic strategy for osteoporosis

Osteoporosis (OP) is a prevalent chronic bone disorder that causes reduction of bone mass, deterioration of bone microarchitecture, and increase of fragility and fracture risk. Current therapeutic strategies mainly alleviate these pathological features but often fail to fully restore bone quality. Extracellular vesicles (EVs) are nanoscale mediators of intercellular communication and have recently emerged as groundbreaking candidates for restoring bone homeostasis. This review systematically explores the multifaceted potential of EVs as therapeutics, diagnostic biomarkers, and drug delivery systems for OP. EVs from diverse biological sources (<i>e.g.</i>, mammals, plants, and microbial species) are critically evaluated as innovative modulators of bone metabolism. EVs carry dynamic biomarkers of OP progression which not only possess diagnostic value but also provide novel insights into disease mechanisms. Moreover, EVs could be further bioengineered for bone-targeted drug delivery. Indeed, preclinical studies validate the transformative potential of EVs, although challenges remain in clinical translation. We report current advancements, identify translational barriers, and emphasize the need for interdisciplinary collaboration to accelerate the transition from basic research to clinical applications.