Osteogenic Potential of Simvastatin and Fluvastatin in an Organotypic Bone Model

Background/Objectives: Statins, widely prescribed for their lipid-lowering properties, also exert pleiotropic effects on various tissues, including bone. However, their osteogenic potential remains poorly defined due to variability in statin type, dosage, and experimental models. This study investigates the osteogenic effects of fluvastatin (FV) and simvastatin (SV) on the ex vivo embryonic chick femur model. Methods: Femora were cultured with logarithmic concentrations (0.1-10 µM) of FV or SV, followed by characterization via microcomputed tomography, histological analysis, and quantitative gene expression. Results: Both statins enhanced osteogenic outcomes at low concentrations (0.1-1 µM), as evidenced by increased bone volume fraction, trabecular organization, collagen matrix maturation, and mineral deposition. Molecular analysis revealed upregulation of key osteogenic markers-RUNX2, SPP1, and COL1A2-with no significant change in chondrogenic markers (SOX9, ACAN), indicating selective activation of osteogenic pathways. In contrast, higher-dose treatment (10 µM) attenuated these effects. Conclusions: These findings underscore the dose-dependent osteoinductive potential of statins and support their application in bone repair strategies within carefully defined therapeutic windows.