Serum-derived exosomes of young rats protect bone of ovariectomized rats after fatigue loading in vivo

In patients with postmenopausal osteoporosis, the accumulation of bone microdamage further increases fracture risk. Exosomes derived from the circulatory system of young individuals can reverse age-related defects during bone repair. Therefore, the present study aimed to elucidate the mechanisms underlying the protective effects of exosomes against structural degradation under fatigue-induced damage. To this end, a rat tibial fatigue injury model was established to investigate the protective effects of serum-derived exosomes (SDEs) isolated from young rats on bone after fatigue damage. SDEs were administered via intramedullary injection for 3 wk. The results demonstrated that treatment with SDEs significantly alleviated bone microdamage in ovariectomized rats. Specifically, it decreased cortical bone microcrack density and increased the mineral apposition rate significantly. In the distal trabecular bone region, treatment with SDEs increased bone volumetric bone mineral density (vBMD) and decreased trabecular spacing (Tb.Sp) significantly, with no significant changes in the structure model index. This study revealed that SDEs can rapidly repair fatigue-damaged bone microstructure, improving microstructural parameters in non-weight-bearing (distal tibial) cancellous bone (increased vBMD and decreased Tb.Sp). These findings provide a potential novel strategy for early intervention of microdamage in postmenopausal osteoporosis.