Francesco D'Aiuto

Short-term Effects of Intensive Periodontal Therapy on Serum Inflammatory Markers and Cholesterol

Severe periodontitis has been associated with increased systemic inflammation. In a three-arm preliminary randomized trial, we investigated the impact of standard (SPT) and intensive periodontal therapy (IPT) on serum inflammatory markers and cholesterol levels. Medical and periodontal parameters, C-reactive protein (CRP), interleukin-6 (IL-6), total cholesterol, and LDL cholesterol were evaluated in 65 systemically healthy subjects suffering from severe generalized periodontitis. Two months after treatment, both SPT and IPT resulted in significant reductions in serum CRP compared with the untreated control (0.5 ± 0.2 mg/L for SPT, P = 0.030 and 0.8 ± 0.2 mg/L for IPT, P = 0.001). Similar results were observed for IL-6. Changes in inflammation were independent of age, gender, body mass index, and ethnicity, but a significant interaction between cigarette smoking and treatment regimen was found. The IPT group also showed a decrease in total and LDL cholesterol after 2 months. Analysis of these data indicates that periodontitis causes moderate systemic inflammation in systemically healthy subjects.

Association between overweight/obesity and periodontitis in adults. A systematic review

Overweight and obesity have been suggested to be associated with periodontitis as published in studies and narrative summaries. This project presents results of a systematic review investigating the association between overweight or obesity (as defined by the World Health Organization) and periodontitis.

Oxidative Stress, Systemic Inflammation, and Severe Periodontitis

Periodontal infections have been associated with a state of chronic inflammation. To ascertain whether severe periodontitis and its treatment are associated with oxidative stress, we recruited 145 cases (periodontitis) and 56 controls in a case-control study. A further pilot intervention study of 14 cases (periodontal therapy) was performed. Blood samples were taken at baseline (case-control) and 1, 3, 5, 7, and 30 days after treatment (intervention). Diacron-reactive oxygen metabolites (D-ROM), anti-oxidant potential, C-reactive protein (CRP), interleukin-6, and lipid profiles were determined with high-sensitivity assays in serum. Patients with severe periodontitis exhibited higher D-ROM levels (P < 0.001) and lower total anti-oxidant capacity (P < 0.001) compared with healthy control individuals. These findings were independent of age, gender, smoking habits, ethnicity, and standard lipids differences. D-ROM levels were positively correlated with CRP (R = 0.4, P < 0.001) and clinical periodontal parameters (R = 0.20, P < 0.05). Acute increases of D-ROM (P < 0.01) were observed following periodontal therapy. Analysis of these data suggests a positive association between severe periodontitis and oxidative stress.

Association of the Metabolic Syndrome with Severe Periodontitis in a Large U.S. Population-Based Survey

CONTEXT Metabolic syndrome and periodontitis both have an increasing prevalence worldwide; however, limited information is available on their association. OBJECTIVE The objective of the study was to assess the association between periodontitis and the metabolic syndrome in a cross-sectional survey of a nationally representative sample of the noninstitutionalized civilians in the United States. DESIGN, SETTING, AND PARTICIPANTS Data analysis from the Third National Health and Nutrition Examination Survey on 13,994 men and women aged 17 yr or older who received periodontal examination were studied. MAIN OUTCOME MEASURES Association of diagnosis and extent of periodontitis (gingival bleeding, probing pocket depths) with the metabolic syndrome and its individual component conditions (central obesity, hypertriglyceridemia, low high-density lipoprotein-cholesterol, hypertension, and insulin resistance) were measured. Adjustment for age, sex, years of education, poverty to income ratio, ethnicity, general conditions, and smoking were considered. RESULTS The prevalence of the metabolic syndrome was 18% [95% confidence interval (CI) 16-19], 34% (95% CI 29-38), and 37% (95% CI 28-48) among individuals with no-mild, moderate, and severe periodontitis, respectively. After adjusting for confounders, participants aged older than 45 yr suffering from severe periodontitis were 2.31 times (95% CI 1.13-4.73) more likely to have the metabolic syndrome than unaffected individuals. Diagnosis of metabolic syndrome increased by 1.12 times (95% CI 1.07-1.18) per 10% increase in gingival bleeding and 1.13 times (95% CI 1.03-1.24) per 10% increase in the proportion of periodontal pockets. CONCLUSIONS Severe periodontitis is associated with metabolic syndrome in middle-aged individuals. Further studies are required to test whether improvements in oral health lead to reductions in cardiometabolic traits and the risk of metabolic syndrome or vice versa.

Treatment of periodontitis improves the atherosclerotic profile: a systematic review and meta‐analysis

AIM Systematic review and meta-analyses to study the robustness of observations that treatment of periodontitis improves the atherosclerotic profile. MATERIAL AND METHODS Literature was searched in Medline-PubMed, Cochrane CENTRAL and EMBASE, based on controlled periodontal intervention trials, including also a non-intervention group. Data were extracted and meta-analyses were performed. RESULTS From 3928 screened studies, 25 trials met the eligibility criteria. These trials enrolled 1748 periodontitis patients. Seven trials enrolled periodontitis patients that were otherwise healthy, 18 trials recruited periodontal patients with various co-morbidities, such as CVD or diabetes. None of the trials used hard clinical endpoints of CVD. However, improvement of endothelial function has been consistently reported. Meta-analyses demonstrated significant weighted mean difference (WMD) for hsCRP (-0.50 mg/l, 95% CI:-0.78; -0.22), IL-6 (-0.48 ng/l, 95% CI: -0.90; -0.06), TNF-α (-0.75 pg/ml, 95% CI: -1.34; -0.17), fibrinogen (-0.47 g/l, 95% CI: -0.76; -0.17), total cholesterol (-0.11 mmol/l, 95% CI: -0.21; -0.01) and HDL-C (0.04 mmol/l, 95% CI: 0.03; 0.06) favouring periodontal intervention. Importantly, periodontitis patients with co-morbidity benefitted most from periodontal therapy; significant WMD were observed for levels of hsCRP (-0.71 mg/l, 95% CI: -1.05; -0.36), IL-6 (-0.87 ng/l, 95% CI: -0.97; -0.78), triglycerides (-0.24 mmol/l, 95% CI: -0.26; -0.22), total cholesterol (-0.15 mmol/l, 95% CI: -0.29; -0.01), HDL-C (0.05 mmol/l, 95% CI: 0.03; 0.06) and HbA1c (-0.43%, 95% CI: -0.60; -0.25). CONCLUSIONS This systematic review and meta-analyses demonstrate that periodontal treatment improves endothelial function and reduces biomarkers of atherosclerotic disease, especially in those already suffering from CVD and/or diabetes.

Evidence that periodontal treatment improves biomarkers and CVD outcomes

AIM The aim of this review was to critically appraise the evidence on the impact of periodontal treatment of cardiovascular diseases (CVDs) biomarkers and outcomes. METHODS A systematic search was performed in Cinhal, Cochrane, Embase and Medline for relevant articles up to July 2012. Duplicate screening and reference hand searching were performed. Data were then summarized and evidence graded in tables. RESULTS The search resulted in: (a) no evidence on the effects of periodontal therapy on subclinical atherosclerosis, serum levels of CD40 ligand, serum amyloid A and monocyte chemoattractant protein-1, (b) limited evidence on the effects of periodontal therapy on arterial blood pressure, leucocyte counts, fibrinogen, tissue necrosis factor-α, sE-selectin, von Willebrand factors, d-dimers, matrix metalloproteinases, oxidative stress and CVD events, and (c) moderate evidence suggesting a negligible effect of periodontal therapy in reducing interleukin-6 and lipids levels, whilst a positive effect in reducing serum C-reactive protein levels and improving endothelial function. CONCLUSIONS Periodontal therapy triggers a short-term inflammatory response followed by (a) a progressive and consistent reduction of systemic inflammation and (b) an improvement in endothelial function. There is however limited evidence that these acute and chronic changes will either increase or reduce CVD burden of individuals suffering from periodontitis in the long term.

Oral health and cognitive function in the Third National Health and Nutrition Examination Survey (NHANES III).

Objectives: To investigate the association between oral health and cognitive function in early-, mid-, and late-adult life. Methods: A secondary analysis was carried out of a large, well-characterized community sample (NHANES III). Analyzed variables included three measures of oral health (gingival bleeding, loss of periodontal attachment, loss of teeth) and three measures of cognitive function: the Symbol Digit Substitution Test (SDST), the Serial Digit Learning Test (SDLT) (both in 5138 participants aged 20–59 years), and a Story Recall test (in 1555 participants aged ≥70 years). Other covariates in linear regression models included age, gender, ethnicity, education and poverty, and cardiovascular risk factors. Results: Worse scores on all three measures of oral health status were significantly associated with poorer performance on all three measures of cognitive function after adjustment for age. Education was an important confounding factor. However, after full adjustment for all other covariates, gingival bleeding (%) and loss of periodontal attachment (%) remained associated with relative impairment on SDST score (B coefficients both = 0.003), and gingival bleeding was associated with relative impairment on SDLT (B = 0.017). No effect modification by age was observed. Conclusions: Poor oral health is associated with worse cognitive function throughout adult life. This may, in part, be accounted for by early life education and social status. However, the possibility of direct causal pathways requires further investigation. NHANES III = Third National Health and Nutrition Examination Survey; SDST = Symbol Digit Substitution Test; SDLT = Serial Digit Learning Test.

Interleukin‐6 in oral diseases: a review

Interleukin-6 (IL-6) is a pleomorphic cytokine involved in a number of physiologic and pathologic processes including response to trauma and infection and development and progression of inflammation and malignancy. IL-6 is emerging as an important mediator and novel therapeutic target for chronic inflammatory diseases and cancer. The present study reviews the available evidence regarding the association between IL-6 and a range of oral diseases including infections (periodontal disease and endodontic infections), immunologically mediated disorders (oral lichen planus and Sjögrens syndrome) and malignancy (oral cancer and precancer). The role of common genetic variants of IL-6 in determining individual susceptibility to certain oral diseases, as well as novel therapeutic strategies based on IL-6 inhibition are also discussed.

Association between periodontitis and common variants in the promoter of the interleukin-6 gene

We recently reported an association between interleukin-6 (IL6) polymorphisms (SNPs) and haplotypes and aggressive periodontitis (AgP). The aim of this study was to investigate this association in a larger cohort of subjects, affected by either aggressive or chronic periodontitis. Five IL6 SNPs were analyzed in 765 subjects (167 generalized aggressive periodontitis, 57 localized aggressive, 310 chronic periodontitis and 231 periodontally healthy). Among Caucasians (n=454) there were moderate associations for -1363T allele (p=0.011) and for -174GG and -1363GG genotypes with diagnosis of periodontitis (respectively, p=0.044, OR=1.6, 95% CI=1.0-2.4, and p=0.017, OR=1.8, 95% CI=1.1-2.8, adjusted for age, gender and smoking). Haplotypes containing the -174G>C, -1363G>T and -1480C>G polymorphisms were associated with diagnosis of periodontitis (p=0.02). Subgroup analysis by disease phenotype showed associations for the localized AgP (LAgP) group and -1480C>G and -6106A>T SNPs (p=0.007 and 0.010, respectively). Among Caucasians the genotypes IL6 -1480 CC and -6106 TT increased the adjusted OR for LAgP (OR=3.09 and 2.27, respectively). This study supports the hypothesis that IL6 polymorphisms and haplotypes are moderately associated with periodontitis, possibly acting through influencing tissue levels of IL6. This association is stronger for LAgP than for other periodontal disease phenotypes.

Radiographic alveolar bone changes following ridge preservation with two different biomaterials

OBJECTIVES The aim of this randomized controlled trial was to evaluate radiographical bone changes following alveolar ridge preservation with a synthetic bone substitute or a bovine xenograft. METHODS Alveolar ridge preservation was performed in 27 patients randomized in two groups. In the test group (n=14), the extraction socket was treated with Straumann bone ceramic(®) (SBC) and a collagen barrier membrane (Bio-Gide(®)), whereas in the control group (n=13) with deproteinized bovine bone mineral and the same barrier. Standardized periapical X-rays were taken at 4 time points, BL: after tooth extraction, GR: immediately after socket grafting, 4M: 16 weeks, 8M: 32 weeks post-operatively. The levels of the alveolar bone crest at the mesial (Mh), and distal (Dh) and central aspects of the socket were measured at all time points. All the radiographs obtained were subtracted from the follow-up images. The gain, loss and unchanged areas in terms of grey values were tested for significant difference between the two groups. RESULTS In the test group, the Mh and Dh showed a mean difference (± standard deviation) of 0.9 ± 1.2 and 0.7 ± 1.8 mm, respectively, among BL-8M. In the control group, the Mh and Dh showed a mean difference of 0.4 ± 1.3 and 0.7 ± 1.3 mm, respectively (P>0.05). Both treatments presented similar gain in grey values between BL-GR, BL-4M and BL-8M. The SBC presented less loss in grey values between BL-4M and BL-8M (P<0.05). Radiographic assessment underestimated the intrasurgical measurements (mesial and distal) of an average 0.3 mm (95% CI, 0.02-0.6). CONCLUSION Both types of bone grafts presented similar radiographic alveolar bone changes when used for alveolar ridge preservation.