Association of Simvastatin and Hyperlipidemia With Periodontal Status and Bone Metabolism Markers

Resumen

Background: The objective of this study is to determine whether simvastatin consumption and hyperlipidemia are associated with a worse periodontal condition and specific bone activity biomarkers. Methods: This cross-sectional and analytic study includes 73 patients divided into three groups: 1) simvastatin-treated patients with hyperlipidemia (n = 29); 2) patients with hyperlipidemia treated by diet alone (n = 28); and 3) normolipidemic patients (controls, n = 16). The periodontal clinical variables of all participants were gathered, a blood sample was drawn from each to determine the lipid profile (total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein), serum levels of acute-phase reactants (C-reactive protein), erythrocyte sedimentation rate, and bone metabolism markers (osteoprotegerin [OPG], osteocalcin, procollagen type I N-terminal propeptide, and C-terminal telopeptide of type I collagen). Results: The mean ESR was higher in the diet-treated patients with hyperlipidemia than in the normolipidemic controls (P = 0.04). Serum OPG concentrations were significantly higher in the simvastatin-treated patients with hyperlipidemia than in the diet-treated patients with hyperlipidemia (P = 0.05). Multivariable linear regression analysis adjusted for age, sex, tobacco, and alcohol revealed that, compared with the normolipidemic patients, the simvastatin-treated patients with hyperlipidemia showed a mean reduction of 0.8 mm (95% confidence interval = -1.5 to 0.0, P = 0.05) in clinical attachment loss. Conclusions: Within the limits of this study, the findings suggest that the intake of simvastatin is associated with increasing serum OPG concentrations, and this could have a protective effect against bone breakdown and periodontal attachment loss. The baseline systemic inflammatory state of patients with hyperlipidemia is indicated by their increased erythrocyte sedimentation rate. Periodontitis is an infectious disease that affects the tooth-supporting tissues and exhibits a wide range of clinical, microbiologic, and immunologic manifestations. It is associated with and probably caused by a multifaceted dynamic interaction among specific infectious agents, host immune responses, hazardous environmental exposure, and genetic propensity.1 The available scientific evidence appears to indicate an association between hyperlipidemia and periodontitis.2,3 Researchers demonstrated the capacity of periodontal pathogens to alter the lipid profile, increasing low-density lipoprotein (LDL), very low-density lipoprotein, and total cholesterol levels and reducing high-density lipoprotein (HDL) levels.4 It has also been reported that periodontal treatment improves the lipid profile.5 Studies showed that periodontal pathogens affect the oxidative processes of different lipoproteins6 and increase the expression of foam cell LDL receptor.7 Conversely, an altered lipid profile has been associated with the expression of systemic proinflammatory cytokines5,8 and heat shock proteins,9 which affect the pathogenesis of periodontitis. Only two publications have linked periodontal probing depth (PD) with total cholesterol and LDL levels.10,11 Statins may exert an impact at the periodontal level by three different mechanisms. First, their hypolipidemic effect would lead to an indirect improvement of periodontal variables by decreasing the lipid values, as noted above. Second, they also exert a direct anti-inflammatory action through a decrease in proinflammatory cytokines via inhibition of the mevalonate pathway.11-13 Finally, they may have an effect on bone metabolism, although research results have been controversial.14,15 Studies in rodents have shown that certain types of statin (simvastatin and atorvastatin) can stimulate embryonic stem cells toward osteogenic differentiation lines and can inhibit bone resorption.16 This evidence leads some authors, such as Fentog(lu et al.,17 to consider that periodontal treatment combined with statins can contribute to greater hyperlipidemia control. However, the available evidence is not yet sufficiently consistent to confirm the effect of statins on periodontal support tissues in humans, given that most evidence to date is based on animal or in vitro models, with only two clinical studies.11,18 The objective of the present study is to determine whether simvastatin consumption and hyperlipidemia are associated with a worse periodontal condition and with specific bone activity biomarkers.