Simvastatin intervention mitigates hypercholesterolemia-induced alveolar bone resorption in rats

Simvastatin promotes bone formation and increases bone mineral density in patients with hyperlipidemia and ameliorates hypercholesterolemia-induced microstructure changes in the jaw bone of animals. However, whether and how treatment with simvastatin can modulate the hypercholesterolemia-induced alveolar bone resorption is unclear. The present study aimed to examine the therapeutic efficacy and potential mechanisms of simvastatin application in hypercholesterolemia-induced alveolar bone resorption. The association between hyperlipidemia and alveolar bone resorption in 100 patients with periodontitis was examined. Additionally, male Sprague-Dawley rats were fed a standard rodent chow (NC) for 32 weeks or a high cholesterol diet (HCD) for 24 weeks. The HCD-fed rats were randomized, continually fed with HCD and treated with vehicle saline (HC) or simvastatin by gavage (5 mg/kg; SIM, n=10/group) for 8 weeks. The morphological changes to alveolar bone resorption in rats were analyzed by linear measurements. The relative levels of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand RANKL, nuclear factor-κB (NF-κB), microtubule-associated protein 1 light chain 3 (LC3) and p62 in the alveolar bone tissues were determined by reverse transcription-quantitative PCR and/or immunohistochemistry. Sulcus bleeding index (SBI), clinical attachment loss (CAL), probing depth (PD) and the distance of cemantoenamel junction-alveolar bone crest (CEJ-ABC) in patients with hyperlipidemia were significantly greater than that in the controls (P<0.001). The levels of hyperlipidemia were positively correlated with the values of SBI, CAL, PD and CEJ-ABC in this population. Compared with the NC rats, higher levels of alveolar bone resorption, NF-κB expression, higher ratios of RANKL/OPG mRNA transcripts and LC3 to p62 expression were detected in the alveolar bone tissues of HC group. Simvastatin intervention significantly mitigated hypercholesterolemia-induced alveolar bone loss and RANKL mRNA transcription, but increased the ratios of LC3/p62 protein expression in the alveolar bone tissues of rats. Hyperlipidemia is associated with alveolar bone resorption and simvastatin treatment alleviated the hypercholesterolemia-related alveolar bone loss by down-regulating the NF-κB expression.