• High-fat diet induced elevated serum remnant cholesterol levels in mice, leading to significant degeneration of trabecular bone microstructure, including reduced bone density and volume fraction.
• Remnant cholesterol levels were negatively correlated with bone mineral density, bone volume fraction, and trabecular number, and positively correlated with structure model index and trabecular separation.
• Elevated remnant cholesterol suppressed osteogenic gene expression (Runx2, Col1a1, OCN, ALP, OPG) and enhanced osteoclastogenic gene expression (NFATc1, Cathepsin K), indicating an imbalance in bone turnover.
• Despite microstructural deterioration, biomechanical properties (elastic modulus and maximum stress) of the femur were not significantly altered, suggesting early-stage bone quality impairment.