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      Comparative evaluation of efficacy of subgingivally delivered 1.2% Atorvastatin and 1.2% Simvastatin in the treatment of intrabony defects in chronic periodontitis: a randomized controlled trial

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          Abstract

          Background. Statins are the recently evolved agents that aid in periodontal regeneration and ultimately in attaining periodontal health. Atorvastatin (ATV) and Simvastatin (SMV) are specific competitive inhibitors of 3-hydroxy-2-methyl-glutaryl coenzyme A reductase. The current study was conducted to compare the effectiveness of 1.2% ATV and 1.2% SMV, in addition to scaling and root planing (SRP), in the treatment of intrabony defects in subjects with chronic periodontitis.

          Methods. Ninety-six individuals were categorized into three treatment groups: SRP plus 1.2% ATV, SRP plus 1.2% SMV and SRP plus placebo. Clinical parameters of full-mouth plaque index (PI), modified sulcus bleeding index (mSBI), probing depth (PD), and relative attachment level (RAL) were recorded at baseline before SRP and at 3, 6 and 9 months. Bone fill was assessed using percentage radiographic defect depth reduction at baseline, 6 months and 9 months.

          Results. Both ATV and SMV showed significant PD reduction and RAL gain than placebo. ATV group showed greater mean PD reduction and mean RAL gain as compared to SMV group at 3, 6 and 9 months. Furthermore, ATV group sites exhibited a significantly greater percentage of radiographic defect depth reduction (33.23 ± 3.11%; 34.84 ± 3.07%) as compared to SMV (30.39 ± 3.36%; 32.15 ± 3.37%) at 6 and 9 months.

          Conclusion. ATV resulted in greater improvements in clinical parameters with higher percentage of radiographic defect depth reduction as compared to SMV in the treatment of intrabony defects in CP subjects.

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          Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study)

          The objective of this multicenter, randomized, open-label, parallel-group, 8-week study was to evaluate the comparative dose efficacy of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor atorvastatin 10, 20, 40, and 80 mg compared with simvastatin 10, 20, and 40 mg, pravastatin 10, 20, and 40 mg, lovastatin 20, 40, and 80 mg, and fluvastatin 20 and 40 mg. Investigators enrolled 534 hypercholesterolemic patients (low-density lipoprotein [LDL] cholesterol > or = 160 mg/dl [4.2 mmol/L] and triglycerides < or = 400 mg/dl [4.5 mmol/L]). The efficacy end points were mean percent change in plasma LDL cholesterol (primary), total cholesterol, triglycerides, and high-density lipoprotein cholesterol concentrations from baseline to the end of treatment (week 8). Atorvastatin 10, 20, and 40 mg produced greater (p < or = 0.01) reductions in LDL cholesterol, -38%, -46%, and -51%, respectively, than the milligram equivalent doses of simvastatin, pravastatin, lovastatin, and fluvastatin. Atorvastatin 10 mg produced LDL cholesterol reductions comparable to or greater than (p < or = 0.02) simvastatin 10, 20, and 40 mg, pravastatin 10, 20, and 40 mg, lovastatin 20 and 40 mg, and fluvastatin 20 and 40 mg. Atorvastatin 10, 20, and 40 mg produced greater (p < or = 0.01) reductions in total cholesterol than the milligram equivalent doses of simvastatin, pravastatin, lovastatin, and fluvastatin. All reductase inhibitors studied had similar tolerability. There were no incidences of persistent elevations in serum transaminases or myositis.
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            Clinical effect of subgingivally delivered simvastatin in the treatment of patients with chronic periodontitis: a randomized clinical trial.

            Periodontitis is an inflammatory disease that results in bone resorption creating bony defects, which may cause tooth loss. Various drugs have been studied using local delivery to improve the periodontal health and to achieve periodontal regeneration. Simvastatin (SMV) is a specific competitive inhibitor of 3-hydroxy-2-methyl-glutaryl coenzyme A reductase. The present study was designed to investigate the effectiveness of SMV, 1.2 mg, in an indigenously prepared biodegradable controlled-release gel as an adjunct to scaling and root planing (SRP) in the treatment of chronic periodontitis. Sixty patients were categorized into two treatment groups: SRP plus placebo (group 1) and SRP plus SMV, 1.2 mg (group 2). Clinical parameters were recorded at baseline before SRP and at 1, 2, 4, and 6 months; they included modified sulcus bleeding index (mSBI), probing depth (PD), and clinical attachment level (CAL). At baseline and after 6 months, radiologic assessment of intrabony defect (IBD) fill was done using computer-aided software. The mean concentration of SMV in gingival crevicular fluid was estimated by reverse-phase high-performance liquid chromatography. All subjects tolerated the drug, without any postapplication inflammation. Both therapies resulted in significant improvements. The decrease in mSBI score at 6 months was greater in group 2 (2.3267 +/- 0.8017) compared to group 1 (0.5033 +/- 0.6815). The mean decrease in PD from baseline to 6 months was 1.20 +/- 1.24 mm and 4.26 +/- 1.59 mm in groups 1 and 2, respectively. Mean CAL gain from baseline to 6 months was 1.63 +/- 1.99 mm and 4.36 +/- 1.92 mm in groups 1 and 2, respectively. In group 2, there was greater decrease in mean IBD (1.41 +/- 0.74 mm or 32.54%) compared to group 1 (0.09 +/- 0.58 mm or 2.16%). There was a greater decrease in gingival index and PD and more CAL gain with significant IBD fill at sites treated with SRP plus locally delivered SMV in patients with chronic periodontitis.
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              Statins augment vascular endothelial growth factor expression in osteoblastic cells via inhibition of protein prenylation.

              Statins such as simvastatin are 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors that inhibit cholesterol synthesis. We presently investigated statin effects on vascular endothelial growth factor (VEGF) expression in osteoblastic cells. Hydrophobic statins including simvastatin, atorvastatin, and cerivastatin-but not a hydrophilic statin, pravastatin-markedly increased VEGF mRNA abundance in nontransformed osteoblastic cells (MC3T3-E1). Simvastatin (10(-6) M) time-dependently augmented VEGF mRNA expression in MC3T3-E1 cells, mouse stromal cells (ST2), and rat osteosarcoma cells (UMR-106). According to heterogeneous nuclear RNA and Northern analyses, 10(-6) M simvastatin stimulated gene expression for VEGF in MC3T3-E1 cells without altering mRNA stability. Transcriptional activation of a VEGF promoter-luciferase construct (-1128 to +827), significantly increased by simvastatin administration. As demonstrated by gel mobility shift assay, simvastatin markedly enhanced the binding of hypoxia-responsive element-protein complexes. These results indicate that the stimulation of the VEGF gene by simvastatin in MC3T3-E1 cells is transcriptional in nature. VEGF secretion into medium was increased in MC3T3-E1 by 10(-6) M simvastatin. Pretreating MC3T3-E1 cells with mevalonate or geranylgeranyl pyrophosphate, a mevalonate metabolite, abolished simvastatin-induced VEGF mRNA expression; manumycin A, a protein prenylation inhibitor, mimicked statin effects on VEGF expression. The effect of simvastatin was blocked by pretreatment with wortmannin and LY294002, specific phosphatidylinositide-3 kinase inhibitors. Simvastatin enhanced mineralized nodule formation in culture, whereas coincubation with mevalonate, geranylgeranyl pyrophosphate, LY294002, or VEGF receptor 2 inhibitor (SU1498) abrogated statin-induced mineralization. Thus, statins stimulate VEGF expression in osteoblasts via reduced protein prenylation and the phosphatidylinositide-3 kinase pathway, promoting osteoblastic differentiation.
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                Author and article information

                Journal
                J Dent Res Dent Clin Dent Prospects
                J Dent Res Dent Clin Dent Prospects
                J Dent Res Dent Clin Dent Prospects
                JODDD
                TBZMED
                Journal of Dental Research, Dental Clinics, Dental Prospects
                Tabriz University of Medical Sciences
                2008-210X
                2008-2118
                Winter 2017
                15 March 2017
                : 11
                : 1
                : 18-25
                Affiliations
                1Department of Periodontics, Dr. D.Y. Patil Dental College and Hospital, Pimpri, Pune, India
                2Department of Periodontics, Vydehi Institute of Dental Sciences and Research Centre, Bangalore, India
                3Department of Periodontics, Government Dental College & Research Institute, Bangalore, India
                Author notes
                [* ]Corresponding Author;E-mail: periodonticsgdcri@ 123456gmail.com
                Article
                10.15171/joddd.2017.004
                5390121
                28413591
                d5683df6-64c0-40ff-a704-6c442f259cc7
                © 2017 Martande et al.

                This is an Open Access article published and distributed by Tabriz University of Medical Sciences under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 May 2015
                : 05 July 2016
                Categories
                Original Article

                Dentistry
                atorvastatin,bone regeneration,clinical trial,scaling and root planing,simvastatin
                Dentistry
                atorvastatin, bone regeneration, clinical trial, scaling and root planing, simvastatin

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