Association Between Periodontitis and Salivary Nitric Oxide Metabolites Among Community Elderly Koreans

Background: Nitric oxide (NO) is known to play an important role in many biologic systems, although the relationship between NO metabolites and periodontitis remains controversial. Moreover, little evidence of an association between salivary NO (S‐NO) and periodontitis in the general population has been reported. This study aims to investigate the relationship between S‐NO and periodontitis in an elderly Korean population. Methods: A cross‐sectional study was conducted using participants and salivary samples from Sunchang Elderly Cohort Study. The total number of final participants was 242 (91 males and 151 females; 48 to 93 years old). Periodontitis was determined by a clinical attachment loss of >6 mm at six probe points on 12 index teeth. NO was measured in unstimulated saliva via the Griess reaction. Sociodemographic status, general/oral health, and health‐related behaviors were investigated as confounders. Bivariate analysis and multivariable linear regression analyses including confounders were applied. Results: After controlling for age, sex, education, salivary flow rate, number of teeth, smoking status, physical activity, hypertension, and diabetes, three metabolites of S‐NO (total NO, nitrite, and nitrate) were independently associated with the percentage of probe points exhibiting periodontitis. Of these linear associations, total NO was found to have the strongest correlation with periodontitis (partial r = 0.181, P = 0.009). These associations were most pronounced in females (except for nitrate), non‐smokers, those without hypertension, and those without diabetes. Conclusions: Our data suggest that high concentrations of S‐NO are associated with severe periodontitis. Thus, S‐NO may serve as a potential biologic marker for detecting and monitoring periodontitis.     

Elevated Plasma Homocysteine Levels in Chronic Periodontitis: A Hospital‐Based Case‐Control Study

Background: Plasma homocysteine (Hcy), a novel risk factor for cardiovascular disease, has been found to be increased in inflammatory diseases, such as rheumatoid arthritis. Our study investigates the association between chronic periodontitis and plasma Hcy. Methods: This case‐control study involves 85 age‐ and sex‐matched subjects with chronic periodontitis and 91 healthy controls. Patients were grouped into moderate and severe periodontitis. Plaque index, calculus component of simplified oral hygiene index, and modified gingival index were recorded. Body mass index, fasting blood sugar, total cholesterol, triglycerides, high‐density lipoprotein, low‐density lipoprotein, very‐low‐density lipoprotein, and plasma Hcy were also assessed. Results: Case and control groups had similar levels of fasting blood sugar, lipid profile, and body mass index. The mean plasma Hcy was found to be 19.22 ± 8.27 and 10.27 ± 2.50 μmol/L for cases and controls, respectively. A significant elevation in plasma Hcy levels was observed in cases (P <0.05). No significant differences were observed in plasma Hcy levels between moderate and severe chronic periodontitis (P = 0.722). Conclusions: Elevated levels of plasma Hcy were observed in patients with chronic periodontitis. Future research should be directed on the effect of periodontal therapy on plasma Hcy levels.     

Effects of periodontal therapy on systemic markers of inflammation in patients with metabolic syndrome: a controlled clinical trial

Background: The systemic inflammation in both metabolic syndrome (MetS) and periodontitis is a common denominator of the association of these conditions with higher risk of atherosclerosis. The current study investigates whether periodontal therapy may reduce systemic inflammation in patients with MetS and reduce cardiovascular risk. Methods: A parallel‐arm, double‐blind, randomized clinical trial of 1‐year duration in patients with MetS and periodontitis was conducted. Participants were randomized to an experimental treatment group (ETG) (n = 82) that received plaque control and root planing plus amoxicillin and metronidazole or to a control treatment group (CTG) (n = 83) that received plaque control instructions, supragingival scaling, and two placebos. Risk factors for cardiovascular disease were recorded; serum lipoprotein cholesterol, glucose, body mass index (BMI), C‐reactive protein (CRP) and fibrinogen concentrations, and clinical periodontal parameters were assessed at baseline and every 3 months until 12 months after therapy. The primary and secondary outcomes were changes in CRP and fibrinogen levels, respectively. Results: The baseline patients’ characteristics of both groups were similar. No significant changes in lifestyle factors, frequency of hypertension, BMI, serum lipoprotein cholesterol, and glucose levels were observed during the study period. The periodontal parameters significantly improved in both groups 3 months after therapy (P = 0.0001) and remained lower than baseline up to 12 months. The improvement of periodontal status was significantly greater in the ETG (P = 0.0001). A multiple linear regression analysis, controlled for sex, smoking, hypertension, and extent of periodontitis, demonstrated that CRP levels decreased with time and that this reduction was significant at 9 (P = 0.024) and 12 (P = 0.001) months in both groups, without difference between the groups. Fibrinogen levels significantly decreased in the ETG at 6 and 12 months but not in the CTG. Conclusion: Reduction of periodontal inflammation either with root planing and systemic antibiotics or with plaque control and subgingival scaling significantly reduces CRP levels after 9 months in patients with MetS.     

Measurement of atherosclerosis markers in patients with periodontitis: a case-control study

Background: It is suggested that periodontitis enhances the process of vascular inflammation leading to atherosclerosis. The present study explores the effect of periodontitis in relation to the clinical and ultrasound markers of carotid atherosclerosis. Methods: Sixty systemically healthy patients >45 years of age (30 with chronic periodontitis and 30 without periodontitis) were studied in a university dental school. Traditional cardiovascular risk factors for atherosclerosis were evaluated. Carotid intima‐media thickness (IMT) was assessed by ultrasound. Results: The internal carotid IMT was 0.77 and 0.81 mm in the periodontal disease and control groups, respectively, with no statistically significant differences between the two groups (P = 0.538). There were significant differences in the presence of carotid atheroma plaques and the severity of periodontitis (P = 0.003). In the logistic regression analysis, significant differences in terms of age and periodontitis were recorded in relation to the presence of atheroma plaques in the carotid intima. Conclusion: The severity of periodontitis was seen to influence the presence of carotid atheroma plaques.     

代谢综合症患者牙周状况的临床研究

目的：分析代谢综合症患者牙周状况,探讨代谢综合症在牙周疾病发生、发展中的意义。方法：选择150例诊断明确的代谢综合症患者为研究组,150例健康人作为对照组。检查记录：菌斑指数（PLI）、探诊深度（PD）、临床附着丧失（CAL）、出血指数（BI）、失牙数并计算牙周位点率。测定龈沟液及血清中白细胞介素-6（IL-6）、C反应蛋白（CRP）、肿瘤坏死因子-α（TNF-α）水平。结果：代谢综合症组患侵袭性牙周炎、慢性牙周炎高于对照组（P〈0．01）;代谢综合症组PD、CAL、重度百分比及失牙数除BI外均高于对照组（P〈0．01）。代谢综合症患者龈沟液中IL-6、TNF-α、CRP水平高于对照组（p〈0．01）,而血清中两组无差异。相关性分析表明：MS组患者血糖水平与PLI、CAL、BI、重度百分比呈正相关（P〈0．01）,腹型（腰围水平）与PD、CAL、PLI重度百分比呈正相关（P〈0．01）。HDL-C水平与PLI、CAL、BI、重度百分比及失牙数正相关。血糖及HDL-C水平与牙周病的发病率正相关。结论：MS患者牙周疾病的发病率明显高于正常人,其中血糖、HDL-C及肥胖程度是影响牙周状况的重要因素,这种变化可能是通过MS引发炎症失衡而发生的。     

Subgingival bacterial clusters and serum antibody response as markers of extent and severity of periodontitis in adult Chinese

This study evaluated the associations between clinical, microbiological, and antibody activity manifestations of periodontitis in 123 adult rural Chinese subjects with no dental intervention. All participants were registered for full‐mouth clinical attachment level (CAL) and pocket probing depth (PD) measurements, and microbial samples were taken from four sites and analyzed for 18 different bacterial species using the ‘checkerboard’. Serum from each individual was analyzed to determine the antibody activity against the same 18 species. Exploratory factor analysis disclosed two microbial factors – Factor 1, consisting of seven species associated with periodontal health (‘early colonizers’); and Factor 2, consisting of eight species associated with periodontitis (‘putative periodontopathogens’) – which explained 87% of the variation among the microbial variables. Factor 2 was consistently associated with disease‐severity measures, whereas the ‘early colonizer’ factor was not. The antibody response showed weak or no correlations with bacterial load or with disease severity. We conclude that the bacteria investigated are resident in the subgingival plaque; that their load and proportions in the pocket may be ecologically driven; and that the antibody response is based on bacterial carrier state rather than on disease. The different antibody‐response pattern found between the individuals may suggest that each individual could be classified as a good or a weak immune responder.     

Effect of Non‐Surgical Periodontal Therapy on Serum Ferritin Levels: An Interventional Study

Background: Ferritin, an acute‐phase reactant, has been found to be elevated in many chronic inflammation‐related diseases. The aim of the present study is to investigate differences in concentrations of serum ferritin in patients with and without periodontal disease before and after non‐surgical periodontal therapy and correlate these values with clinical variables associated with periodontal disease. Methods: Forty‐two individuals were included in this study, 20 with chronic periodontitis (CP) and 22 classified as periodontally healthy. Serum ferritin concentrations, hemoglobin levels, and periodontal parameters (probing depth [PD], clinical attachment level, gingival index, bleeding on probing, and plaque index) were recorded at baseline and 3 months after non‐surgical periodontal therapy. Results: Patients with CP showed higher concentrations of serum ferritin than periodontally healthy controls (P <0.01). After adjustment for confounders, a positive and significant correlation was observed between serum ferritin levels and the number of sites with PD ≥6 mm at baseline (P <0.01). Regression analyses revealed association between deep pockets and serum ferritin levels at baseline (R² = 0.823). Significant reductions in serum ferritin levels were observed at the 3‐month assessment after periodontal treatment (P <0.01), and the post‐treatment serum ferritin values were comparable to those of controls (P >0.05). Furthermore, the post‐treatment degree of change in the serum ferritin level was positively and significantly associated with improvement in PD (R² = 0.213, P <0.05). Conclusion: Serum ferritin levels are raised in patients with CP and decrease to control levels post‐treatment.     

侵袭性牙周炎基础治疗前后全身炎症标志物的变化

目的:探索侵袭性牙周炎(AgP)患者基础治疗前后外周血C-反应蛋白(CRP)和血清蛋白指标的变化特点.方法:临床上收集35例AgP患者,完成3个月的基础治疗后,在基线和3个月后记录牙周临床指标:探诊深度(PD)、探诊出血(BOP)、附着丧失(AL)和牙齿松动度,并抽取外周血进行CRP和总蛋白、白蛋白及白/球蛋白比例的检测.35例年龄性别与实验组相对应的无牙周炎的健康志愿者作为对照组.结果:实验组治疗后临床指标有所改善(P＜0.05),外周血CRP和球蛋白比治疗前降低(P＜0.01),而白蛋白及白/球蛋白比例较治疗前有所升高(P＜0.01).结论:AgP患者经牙周基础治疗后引起外周血血清蛋白指标变化,提示某些全身炎症标志物可能反映AgP的疾病状态.     

Expression of Protease Activated Receptor‐1 in Chronic Periodontitis

Background: Protease activated receptor‐1 (PAR₁) activation by thrombin may play a role in repair and homeostasis of periodontal tissues. The main objective of this study is to investigate PAR₁ expression in patients with periodontitis, before and after non‐surgical periodontal treatment, and to associate its expression with the presence of inflammatory biomarkers and PAR₂ expression. Methods: Gingival crevicular fluid (GCF) samples and clinical parameters, including probing depth, clinical attachment level, bleeding on probing, and gingival and plaque indices, were collected from periodontally healthy individuals and patients with moderate chronic periodontitis (CP) before and 6 weeks after periodontal non‐surgical treatment. PAR₁ and PAR₂ messenger RNA (mRNA) at the GCF were evaluated by quantitative polymerase chain reaction (qPCR). Flow cytometry analysis identified the GCF PAR₁‐expressing cells. GCF inflammatory biomarkers were also determined. Results: Clinical parameters were significantly improved after therapy (P <0.01). The qPCR analysis showed that, before therapy, PAR₁ mRNA levels in CP were similar to controls. Periodontal treatment led to increased PAR₁ expression in CP (P <0.05). PAR₁ expression was inversely correlated to PAR₂ expression and with interleukins 6 and 8, tumor necrosis factor‐α, interferon‐γ, and matrix metalloproteinase‐2 levels. Conclusions: Periodontal treatment results in PAR₁ overexpression in the GCF, and PAR₁ expression is associated with decreased expression of inflammatory biomarkers and inversely correlated to PAR₂ expression in the GCF. Therefore, the data suggest the importance of PAR₁ mediating the known anabolic actions of thrombin in the periodontium.     

Validation of Periodontitis Screening Model Using Sociodemographic,Systemic, and Molecular Information in a Korean Population

Background: This study aims to evaluate and validate a periodontitis screening model that includes sociodemographic, metabolic syndrome (MetS), and molecular information, including gingival crevicular fluid (GCF), matrix metalloproteinase (MMP), and blood cytokines. Methods: The authors selected 506 participants from the Shiwha‐Banwol cohort: 322 participants from the 2005 cohort for deriving the screening model and 184 participants from the 2007 cohort for its validation. Periodontitis was assessed by dentists using the community periodontal index. Interleukin (IL)‐6, IL‐8, and tumor necrosis factor‐α in blood and MMP‐8, ‐9, and ‐13 in GCF were assayed using enzyme‐linked immunosorbent assay. MetS was assessed by physicians using physical examination and blood laboratory data. Information about age, sex, income, smoking, and drinking was obtained by interview. Logistic regression analysis was applied to finalize the best‐fitting model and validate the model using sensitivity, specificity, and c‐statistics. Results: The derived model for periodontitis screening had a sensitivity of 0.73, specificity of 0.85, and c‐statistic of 0.86 (P <0.001); those of the validated model were 0.64, 0.91, and 0.83 (P <0.001), respectively. Conclusions: The model that included age, sex, income, smoking, drinking, and blood and GCF biomarkers could be useful in screening for periodontitis. A future prospective study is indicated for evaluating this model's ability to predict the occurrence of periodontitis.     

Effect of treatment of chronic periodontitis on levels of serum markers of acute-phase inflammatory and vascular responses

AIMS: Recent epidemiological work suggests an association between periodontal disease severity and cardiovascular disease risk. This study aimed to ascertain if circulating levels of cardiovascular and systemic inflammatory markers could be modified following treatment of periodontal disease. METHOD: Adult subjects were recruited from those awaiting periodontal treatment and randomised to either immediate (test, n=24) or delayed treatment (control, n=15). Demographic and clinical data were collected and venous blood was taken before and either 6 weeks after completion of treatment or after an equivalent 3-month control period. Periodontal examination included probing depth, loss of attachment, plaque scores and bleeding scores. Blood was analysed to determine serum and plasma fibrinogen, C-reactive protein, sialic acid, tumour necrosis factor-alpha and interleukin -6 and -1beta. Effects of treatment were assessed by paired tests and analysis of variance by treatment group with baseline covariates. RESULTS: Treatment improved plaque and bleeding scores and reduced probing depths (p<0.002). However, there were no statistically significant changes in levels of any of the systemic markers. CONCLUSION: Improvement in periodontal health did not influence the levels of vascular markers.     

The association of periodontal diseases with metabolic syndrome and obesity

Periodontitis is a multifactorial chronic inflammatory disease associated with dysbiotic plaque biofilms and characterized by progressive destruction of the tooth-supporting apparatus. Globally, it is estimated that 740 million people are affected by its severe form. Periodontitis has been suggested to be linked to obesity and metabolic syndrome. Obesity, defined as excessive fat accumulation, is a complex multifactorial chronic inflammatory disease, with a high and increasing prevalence. Metabolic syndrome is defined as a cluster of obesity, dyslipidemia, hypertension, and dysglycemia. Obesity, metabolic syndrome and periodontitis are among the most common non-communicable diseases and a large body of evidence from epidemiologic studies supports the association between these conditions. Extensive research has established plausible mechanisms to explain how these conditions can negatively impact each other, pointing to a bidirectional adverse relationship. At present there is only limited evidence available from a few intervention studies. Nevertheless, the global burden of periodontitis combined with the obesity epidemic has important clinical and public health implications for the dental team. In accordance with the common risk factor approach for tackling non-communicable diseases, it has been proposed that oral healthcare professionals have an important role in the promotion of periodontal health and general well-being through facilitation of healthy lifestyle behaviours.     

Severe periodontitis is associated with systemic inflammation and a dysmetabolic status: a case-control study

BACKGROUND AND AIM: A cluster of metabolic factors defines a syndrome that predisposes to diabetes and cardiovascular disease. Chronic infections such as periodontitis might alter these individual metabolic factors and the systemic inflammatory burden. The aim of this study was to investigate the association between severe periodontitis and increase in inflammatory and metabolic risk factors for cardiovascular disease. MATERIALS AND METHODS: We examined 302 patients with severe periodontitis and 183 healthy controls, and we collected a blood sample from each subject in order to investigate differences in inflammatory (leukocyte numbers and differential counts) and metabolic markers (lipids and glucose). RESULTS: After correcting for differences in age, gender, smoking and ethnicity, periodontitis subjects exhibited a low-grade systemic inflammation (increased white cell counts, 1.10+/-1.02 x 10(9)/l, 95%CI 1.05-1.15, p=0.0001), dyslipidemia [lower high-density lipoprotein cholesterol, 1.14+/-1.03 mmol/l, 95%CI 1.08-1.20, p<0.0001 and higher low-density lipoprotein cholesterol, 1.12+/-1.03, 95%CI 1.05-1.19, p<0.0001) and increased non-fasting serum glucose levels (1.04+/-1.01 mmol/l, 95%CI 1.02-1.06, p=0.01) when compared with controls. The associations were confirmed in a subpopulation of Caucasian non-smokers. A trend for a dose dependent effect of the number of periodontal pockets on the tested inflammatory and metabolic markers was observed. Conclusions: These data suggest a possible link between severe generalized periodontitis, systemic inflammation and a dysmetabolic state in otherwise healthy individuals.     

Curcumin inhibits inflammatory response and bone loss during experimental periodontitis in rats

Abstract

Objective. Curcumin, an active ingredient of turmeric, is proved to be a potential candidate of controlling inflammation and bone resorption, but few reports are on the periodontitis. The purpose of this study was to evaluate whether the intra-gastric administration of curcumin could inhibit the in?ammation and alveolar bone resorption in rats following ligature-induced experimental periodontitis. Materials and method. Male Wistar rats were randomly divided into three groups: no ligature placement and administration of vehicle, ligature placement and administration of vehicle, ligature placement and administration of curcumin. After the animals were sacrificed, their mandibles were collected for morphological, histological and immunohistochemical analysis; their gingival tissues were collected for cytokine measurements. Results. Bone resorption was significantly higher in the experimental periodontitis animals treated with vehicle compared with the curcumin-treated group or the control group. Furthermore, receptor activator of nuclear factor-κB ligand (RANKL), receptor activator of nuclear factor-κB (RANK), osteoprotegerin (OPG), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) expression levels were higher in the experimental periodontitis animals treated with vehicle compared with the curcumin treated group or the control group. Conclusions. Curcumin may decrease alveolar bone loss in the experimental periodontitis rats via suppressing the expression of RANKL/RANK/OPG and its anti-inflammatory properties.     

Therapeutic Effects of Systemic Vitamin K2 and Vitamin D3 on Gingival Inflammation and Alveolar Bone in Rats With Experimentally Induced Periodontitis

Background: The synergistic effects of vitamin D3 and vitamin K2 on bone loss prevention have been reported. This study evaluates the effects of vitamin D3 and vitamin K2 supplementation in conjunction with conventional periodontal therapy (scaling and root planing [SRP]) on gingival interleukin (IL)‐1β and IL‐10, serum bone alkaline phosphatase (B‐ALP) and tartrate‐resistant acid phosphatase 5b (TRAP‐5b), and calcium and alveolar bone levels in rats with experimentally induced periodontitis. Methods: Seventy‐two rats were divided into the following groups: 1) healthy; 2) periodontitis; 3) SRP; 4) SRP + vitamin D3; 5) SRP + vitamin K2; and 6) SRP + vitamins K2 and D3. Periodontitis was induced by ligature placement for 7 days, and vitamin K2 (30 mg/kg) and/or vitamin D3 (2 μg/kg) were administered for 10 days in the SRP + vitamin D3, SRP + vitamin K2, and SRP + vitamins K2 and D3 groups by oral gavage. On day 18, the animals were sacrificed, serum B‐ALP, TRAP‐5b, and calcium levels were measured, gingiva specimens were extracted for IL‐1β and IL‐10 analysis, and distances between the cemento‐enamel junction and alveolar bone crest were evaluated. Results: Alveolar bone levels in the periodontitis group were significantly greater than those in the other five groups. No significant differences were found in gingival IL‐1β and IL‐10, serum B‐ALP and TRAP‐5b, and calcium and alveolar bone levels between the groups receiving SRP and vitamins and the group receiving SRP alone. Conclusion: Within the limitations of this study, vitamin D3 and K2 alone or in combination did not affect gingival IL‐1β and IL‐10, serum B‐ALP and TRAP‐5b levels, or alveolar bone compared with conventional periodontal therapy alone.