Fluvastatin Inhibits Osteoclast Differentiation and Porphyromonas gingivalis Lipopolysaccharide-Induced Alveolar Bone Erosion in Mice.

Background: Statins have been widely used to treat hypercholesterolemia. In addition to inhibition of cholesterol synthesis, recent reports suggest a bone anabolic property of statins. However, little notice has been paid to the direct effect of statins on osteoclastogenesis and bone resorption. Methods: The effect of fluvastatin on osteoclast differentiation was determined using in vitro culture of mouse bone marrow macrophages (BMMs) in the presence of macrophage colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand (RANKL). The role of fluvastatin on bone erosion was examined in the Porphyromonas gingivalis (Pg) lipopolysaccharide (LPS)-induced alveolar bone loss model in mice. Results: Fluvastatin significantly inhibited both RANKL-and LPS-induced osteoclast differentiation in mouse BMMs. Fluvastatin also markedly reduced expression of osteoclast differentiation marker genes Acp5, Calcr, and Ctsk as well as fusion markers Atp6v0d2 and Dcstamp. These were accompanied by decreased expression of c-Fos and nuclear factor of activated T cells cytoplasmic 1 transcription factors. Fluvastatin reduced generation of reactive oxygen species upon the addition of RANKL and LPS, suggesting an antioxidant role. Finally, administration of fluvastatin in mice conspicuously reduced Pg LPS-induced osteoclastogenesis and alveolar bone erosion in vivo. Conclusion: Combined, these results suggest fluvastatin directly inhibited osteoclastogenesis and efficiently blocked bone erosion.