Luigi Nibali

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.

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.

Gene Polymorphisms and the Prevalence of Key Periodontal Pathogens

Growing evidence suggests that individual genetic susceptibility may influence the host’s response to infections. The aim of this project was to study whether gene polymorphisms of inflammatory markers are associated with the presence of viable periodontopathogenic bacteria. We extracted genomic DNA from 45 young adults diagnosed with generalized aggressive periodontitis to study Fc receptors, formyl peptide receptor, Interleukin-6, tumor necrosis factor-α, and vitamin D receptor polymorphisms. The presence and viable numbers of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Tannerella forsythensis were determined by culture, and their identities confirmed by PCR. Multiple logistic regressions revealed that both Fcγ receptor and IL-6 -174 polymorphisms were associated with increased odds of detecting A. actinomycetemcomitans, P. gingivalis, and T. forsythensis after adjustment for age, ethnicity, smoking, and periodontitis extent. These findings support the hypothesis that complex interactions between the microbiota and host genome may be at the basis of susceptibility to aggressive periodontitis.

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.

Principles in prevention of periodontal diseases Consensus report of group 1 of the 11th European Workshop on Periodontology on effective prevention of periodontal and peri-implant diseases

AIMS In spite of the remarkable success of current preventive efforts, periodontitis remains one of the most prevalent diseases of mankind. The objective of this workshop was to review critical scientific evidence and develop recommendations to improve: (i) plaque control at the individual and population level (oral hygiene), (ii) control of risk factors, and (iii) delivery of preventive professional interventions. METHODS Discussions were informed by four systematic reviews covering aspects of professional mechanical plaque control, behavioural change interventions to improve self-performed oral hygiene and to control risk factors, and assessment of the risk profile of the individual patient. Recommendations were developed and graded using a modification of the GRADE system using evidence from the systematic reviews and expert opinion. RESULTS Key messages included: (i) an appropriate periodontal diagnosis is needed before submission of individuals to professional preventive measures and determines the selection of the type of preventive care; (ii) preventive measures are not sufficient for treatment of periodontitis; (iii) repeated and individualized oral hygiene instruction and professional mechanical plaque (and calculus) removal are important components of preventive programs; (iv) behavioural interventions to improve individual oral hygiene need to set specific Goals, incorporate Planning and Self monitoring (GPS approach); (v) brief interventions for risk factor control are key components of primary and secondary periodontal prevention; (vi) the Ask, Advise, Refer (AAR) approach is the minimum standard to be used in dental settings for all subjects consuming tobacco; (vii) validated periodontal risk assessment tools stratify patients in terms of risk of disease progression and tooth loss. CONCLUSIONS Consensus was reached on specific recommendations for the public, individual dental patients and oral health care professionals with regard to best action to improve efficacy of primary and secondary preventive measures. Some have implications for public health officials, payers and educators.

Amoxicillin and metronidazole as an adjunctive treatment in generalized aggressive periodontitis at initial therapy or re‐treatment: a randomized controlled clinical trial

BACKGROUND Previously, we showed that systemic metronidazole and amoxicillin significantly improved the outcomes of non-surgical debridement in generalized aggressive periodontitis patients. This study aimed to observe whether re-treatment with adjunctive antimicrobials would give the placebo group benefits comparable with the test group. METHODS Thirty-eight of 41 subjects, from the initial 6-month trial, completed the second phase, re-treatment of sites with remaining pockets 5 mm. Subjects on placebo in phase one, received adjunctive antibiotics for 7 days. Clinical parameters were collected at 2 months posttreatment (8 months from baseline). RESULTS Patients who received antibiotics at initial therapy, showed statistically significant improvement in pocket depth reduction and in the % of sites improving above clinically relevant thresholds, compared with patients who received antibiotics at re-treatment. In deep pockets (7 mm), the mean difference was 0.9 mm (p=0.003) and in moderate pockets (4-6 mm) it was 0.4 mm (p=0.036). For pockets converting from 5 to 4 mm, this was 83% compared with 67% (p=0.041) and pockets converting from 4 to 3 mm was 63% compared with 49% (p=0.297). CONCLUSIONS At 8 months, patients who had antibiotics at initial therapy showed statistically significant benefits compared with those who had antibiotics at re-treatment.

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.

Regenerative Medicine for Periodontal and Peri-implant Diseases

The balance between bone resorption and bone formation is vital for maintenance and regeneration of alveolar bone and supporting structures around teeth and dental implants. Tissue regeneration in the oral cavity is regulated by multiple cell types, signaling mechanisms, and matrix interactions. A goal for periodontal tissue engineering/regenerative medicine is to restore oral soft and hard tissues through cell, scaffold, and/or signaling approaches to functional and aesthetic oral tissues. Bony defects in the oral cavity can vary significantly, ranging from smaller intrabony lesions resulting from periodontal or peri-implant diseases to large osseous defects that extend through the jaws as a result of trauma, tumor resection, or congenital defects. The disparity in size and location of these alveolar defects is compounded further by patient-specific and environmental factors that contribute to the challenges in periodontal regeneration, peri-implant tissue regeneration, and alveolar ridge reconstruction. Efforts have been made over the last few decades to produce reliable and predictable methods to stimulate bone regeneration in alveolar bone defects. Tissue engineering/regenerative medicine provide new avenues to enhance tissue regeneration by introducing bioactive models or constructing patient-specific substitutes. This review presents an overview of therapies (e.g., protein, gene, and cell based) and biomaterials (e.g., resorbable, nonresorbable, and 3-dimensionally printed) used for alveolar bone engineering around teeth and implants and for implant site development, with emphasis on most recent findings and future directions.

Subgingival microbiota in health compared to periodontitis and the influence of smoking

The etiology of periodontitis has traditionally been associated to a consortium of three bacterial species—the so-called “red-complex” of periodontal disease—which has been the target for most diagnostic and therapeutic strategies. However, other species have also been found to correlate with disease severity. In addition, the influence of smoking on periodontal microbiota is poorly understood. In the current manuscript, the composition of the subgingival microbiota in healthy individuals vs. patients with chronic periodontitis has been investigated using 16S pyrosequencing and the influence of smoking on periodontal composition has been examined. Subgingival bacterial communities were sampled from 82 patients: 22 non-smoking healthy controls, 28 non-smoking periodontal patients, and 32 smoking periodontal patients. Bacterial diversity was higher in periodontal patients than in healthy subjects, which could be interpreted as the consequence of a nutritionally richer environment or a reduced immune competence. Periodontal patients showed a significantly higher prevalence/relative abundance of “established” periopathogens but also other taxa whose role is not well-established and that should be targets for future research. These include Anaeroglobus, Bulleidia, Desulfobulbus, Filifactor, Mogibacterium, Phocaeicola, Schwartzia or TM7. The microbial community of smoking-associated periodontitis is less diverse and distinct from that of non-smokers, indicating that smoking has an influence on periodontal ecology. Interestingly, the high sequencing coverage allowed the detection at low proportions of periodontal pathogens in all healthy individuals, indicating that chronic periodontitis cannot be strictly considered an infectious disease but the outcome of a polymicrobial dysbiosis, where changes in the proportions of microbial consortia trigger the inflammatory and tissue-degradation responses of the host.

Association between interleukin‐6 promoter haplotypes and aggressive periodontitis

BACKGROUND Interleukin-6 (IL-6) polymorphisms have been shown to affect IL-6 promoter activity. This study investigated the possible role of IL-6 genetic polymorphisms and haplotypes in the predisposition to aggressive periodontitis (AgP). MATERIAL AND METHODS A case-control association study on 224 AgP patients and 231 healthy controls was performed in order to detect differences in genotype distributions of five single nucleotide polymorphisms (SNPs) located in the promoter region of the IL-6 gene. RESULTS The IL-6 -1363 polymorphism was associated with a diagnosis of AgP in subjects of all ethnicities (p=0.006, adjusted logistic regression). The -1480 SNP was associated with LAgP in subjects of all ethnicities (p=0.003). The -1480 and -6106 polymorphisms were associated with Localized AgP in Caucasians (n=24) (p=0.007 and 0.010, respectively). Haplotypes determined by the -1363 and -1480 polymorphisms were also associated with LAgP (p=0.001) in Caucasians. CONCLUSIONS This study supports the hypothesis of a link between IL-6 genetic factors and AgP and highlights the importance of two IL-6 polymorphisms (-1363 and -1480) in modulating disease phenotype and susceptibility.