Objective To investigate the effects of pinoresinol diglucoside (PDG) on bone strength in growing mice, aiming to prevent the development of osteoporosis. Methods One-month-old female C57 mice were randomly divided into three groups: Control (equal volume of distilled water), PDG-L (PDG, 36 mg·kg-1·d-1), and PDG-H (PDG, 72 mg·kg-1·d-1), with 15 animals in each group. All animals were sacrificed after 6 weeks. Micro-CT imaging analysis, biomechanical testing, dual fluorescence labeling analysis, serum biochemical markers detection, and bone tissue-related protein expression analysis were conducted. Results PDG administration did not induce significant pathological changes in major organs of the mice. Compared to the Control group, the PDG-L group showed a significant increase in tibial Tb.BMD (P<0.01), with notable increases in Tb.N, Tb.Th, and Tb.BV/TV (P<0.05), and a significant reduction in Tb.Sp (P<0.01). PDG-H group also showed a significant increase in Tb.BMD (P<0.05). The PDG-L group demonstrated significantly higher maximum load and bending modulus of the femur (P<0.01), with a significantly higher bending strength compared to the Control group (P<0.05). The PDG-H group also showed higher maximum load and elastic modulus compared to the Control group (P<0.05). In both PDG groups, tibial cortical bone fluorescence spacing significantly increased (P<0.01), bone formation rate was elevated, and bone mineralization deposition rate accelerated. PDG-L group showed a significant increase in OPG levels compared to the Control group (P<0.01), and a significant decrease in RANKL levels (P<0.01). The expression levels of bone-related proteins BMP2, OSX, and Runx2 were significantly up-regulated in both PDG groups (P<0.01), as well as a significant increase in bone regulatory protein OPG (P<0.01) and a significant decrease in RANKL (P<0.05). Conclusion PDG effectively enhances bone mineral density, optimizes bone microstructure, improves bone quality, promotes bone formation, and inhibits bone resorption, thereby increases bone strength in growing mice. |