M. P. Cullinan

Comparison of the clinical features of chronic and aggressive periodontitis

Overall, while most clinicians would agree that aggressive forms of periodontitis exist as clinical entities, the clinical distinction between chronic and aggressive periodontitis (especially generalized) is not clear cut. This may not be all that significant from a treatment perspective, in so far as individualized anti-infective therapies are effective for both forms of the disease. However, from a research perspective, it is essential that these diseases be clearly distinguished in order to gain a complete understanding of their etiology and pathogenesis. The relative lack of clinical inflammation often associated with the localized molar-and-incisor form of aggressive periodontitis has been commented on for almost 100 years, and it is generally accepted that this form of the disease is associated with a thin biofilm, at least in its early stages. In contrast, the presence of clinical inflammation in generalized aggressive periodontitis appears to be similar to that observed in chronic periodontitis, and in this situation age of onset and family history are important additional criteria for either diagnosis or classification. It is also generally recognized that chronic periodontitis may subsequently be superimposed on both localized and generalized forms of aggressive periodontitis. While this may have little bearing on the treatment of such cases, it could have an enormous impact on both the design and interpretation of research studies, whether basic science or clinical. This highlights the essential difference between a diagnosis and a classification, whereby a diagnosis is the clinicians best guess, leading on to a treatment plan, whereas a classification does not allow such flexibility, requiring non-overlapping case definitions for research purposes if the underlying etiology of these diseases is ever to be fully elucidated.

The immunopathogenesis of periodontal disease

Treatment planning in periodontics, as with any disease, must be based on an understanding of the aetiology and pathogenesis of the disease. In this context, it has slowly become recognized over the past three decades that while plaque is the cause of the disease, it is the innate susceptibility of the host that determines the ultimate outcome of the disease process. Innate susceptibility, in turn, is determined by the nature of the immune response to the specific periodontopathic complexes comprising the plaque biofilm. The aim of this review was to examine current understanding of the immunopathogenesis of chronic periodontitis with respect to its possible clinical implications in terms of treatment planning and risk assessment. Numerous studies have demonstrated that the periodontitis lesion itself involves predominantly B cells and plasma cells, while the gingivitis lesion is primarily a T cell mediated response. This led to the concept over 30 years ago that the development of periodontitis involves a switch from a T cell lesion to one involving large numbers of B cells and plasma cells. It is also well recognized that control of this shift is mediated by a balance between the so-called Th1 and Th2 subsets of T cells, with chronic periodontitis being mediated by Th2 cells. More recently, T regulatory (Treg) and Th17 cells have been demonstrated in periodontal tissues, raising the possibility that these cells are also important in the immunoregulation of periodontal disease. The clinical implications of these observations can be seen in the fact that identification of Th1/Th2 and Treg/Th17 cytokine gene expression in the peripheral blood and salivary transcriptomes is now being trialled as a possible marker of disease susceptibility. If this proves to be the case, a chairside salivary diagnostic could be developed within the next five to 10 years.

Periodontal disease and systemic illness: will the evidence ever be enough?

The concept of focal infection or systemic disease arising from infection of the teeth was generally accepted until the mid-20th century when it was dismissed because of lack of evidence. Subsequently, a largely silo approach was taken by the dental and medical professions. Over the past 20 years, however, a plethora of epidemiological, mechanistic and treatment studies have highlighted that this silo approach to oral and systemic diseases can no longer be sustained. While a number of systemic diseases have been linked to oral diseases, the weight of evidence from numerous studies conducted over this period, together with several systematic reviews and meta-analyses, supports an association between periodontitis and cardiovascular disease, and between periodontitis and diabetes. The association has also been supported by a number of biologically plausible mechanisms, including direct infection, systemic inflammation and molecular mimicry. Treatment studies have shown that periodontal treatment may have a small, but significant, systemic effect both on endothelial function and on glycemic control. Despite this, however, there is no direct evidence that periodontal treatment affects either cardiovascular or diabetic events. Nevertheless, over the past 20 years we have learnt that the mouth is an integral part of the body and that the medical and dental professions need to work more closely together in the provision of overall health care for all patients.

Dental stem cells and their potential role in apexogenesis and apexification

Injury to an immature permanent tooth may result in cessation of dentine deposition and root maturation leaving an open root apex and thin dentinal walls that are prone to fracture. Endodontic treatment is often complicated and protracted with an uncertain prognosis frequently resulting in premature tooth loss. Postnatal stem cells, which are capable of self-renewal, proliferation and differentiation into multiple specialized cell lineages have been isolated and identified within the dental pulp, apical papilla and periodontal ligament. The ability of these cells to produce pulp-dentine and cementum-periodontal ligament complexes in vivo suggest potential applications involving stem cells, growth factors and scaffolds for apexification or apexogenesis. Similar protein expression amongst dental stem cells possibly implicates a common origin; however, the dominant cells to repopulate an open apex will be directed by local environmental cues. A greater understanding of the structure and function of cells within their environment is necessary to regulate and facilitate cellular differentiation along a certain developmental path with subsequent tissue regeneration. This review focuses on development of the apical tissues, dental stem cells and their possible involvement clinically in closing the open root apex. MEDLINE and EMBASE computer databases were searched up to January 2009. Abstracts of all potentially relevant articles were scanned and their contents identified before retrieval of full articles. A manual search of article reference lists as well as a forward search on selected authors of these articles was undertaken. It appears that dental stem cells have the potential for continued cell division and regeneration to replace dental tissues lost through trauma or disease. Clinical applications using these cells for apexogenesis and apexification will be dependent on a greater understanding of the environment at the immature root end and what stimulates dental stem cells to begin dividing and then express a certain phenotype.

Characterization of heat shock protein-specific T cells in atherosclerosis.

ABSTRACT A role for infection and inflammation in atherogenesis is widely accepted. Arterial endothelium has been shown to express heat shock protein 60 (HSP60) and, since human (hHSP60) and bacterial (GroEL) HSP60s are highly conserved, the immune response to bacteria may result in cross-reactivity, leading to endothelial damage and thus contribute to the pathogenesis of atherosclerosis. In this study, GroEL-specific T-cell lines from peripheral blood and GroEL-, hHSP60-, and Porphyromonas gingivalis-specific T-cell lines from atherosclerotic plaques were established and characterized in terms of their cross-reactive proliferative responses, cytokine and chemokine profiles, and T-cell receptor (TCR) Vβ expression by flow cytometry. The cross-reactivity of several lines was demonstrated. The cytokine profiles of the artery T-cell lines specific for GroEL, hHSP60, and P. gingivalis demonstrated Th2 phenotype predominance in the CD4 subset and Tc0 phenotype predominance in the CD8 subset. A higher proportion of CD4 cells were positive for interferon-inducible protein 10 and RANTES, with low percentages of cells positive for monocyte chemoattractant protein 1 and macrophage inflammatory protein 1α, whereas a high percentage of CD8 cells expressed all four chemokines. Finally, there was overexpression of the TCR Vβ5.2 family in all lines. These cytokine, chemokine, and Vβ profiles are similar to those demonstrated previously for P. gingivalis-specific lines established from periodontal disease patients. These results support the hypothesis that in some patients cross-reactivity of the immune response to bacterial HSPs, including those of periodontal pathogens, with arterial endothelial cells expressing hHSP60 may explain the apparent association between atherosclerosis and periodontal infection.

Immediate restoration/loading of immediately placed single implants: is it an effective bimodal approach?

OBJECTIVE To compare systematically the survival and radiographic marginal bone level changes of two immediate implant protocols in the aesthetic region; immediate single implant restoration/loading in extraction sockets (the bimodal approach) compared with the same in healed sites. MATERIAL AND METHODS A literature search of electronic databases, Cochrane Oral Health Groups Trials Register, National Research Register, conference proceedings and abstracts was performed without language restriction up to 1 August 2008. Hand searching included several dental journals and authors were contacted for missing information. Controlled trials that compared immediate restoration/loading of single implants placed in extraction sites with those placed in healed sites were selected. The meta-analysis was prepared according to the guidelines of the Quality of Reporting of Meta-analyses statement. The data were analysed using RevMan version 5.0 software. A fixed effects model was chosen with standardized mean differences for continuous data, and risk ratios for dichotomous data with 95% confidence intervals. RESULTS Ten studies with 629 implants were included. Immediate single implant restoration/loading in extraction sockets in the aesthetic zone was associated with significantly higher risk of implant failure (risk ratio of 3.62, 95% confidence interval 1.15-11.45, P=0.03). However, the bimodal approach showed favourable marginal bone changes after 1 year. CONCLUSION The review and meta-analysis supported the potential advantages offered by this bimodal approach, but indicated a higher risk when compared with immediate restoration/loading in healed ridges. Further long-term, well-conducted, randomized-controlled studies are needed to confirm the validity of this treatment option.

Progression of periodontal disease and interleukin‐10 gene polymorphism

BACKGROUND AND OBJECTIVE Interleukin-10 is a key immunoregulatory cytokine that may be of significance in the immunopathogenesis of chronic inflammatory diseases such as periodontal disease. Molecular genetic studies have defined a number of haplotypes that may be associated with differing levels of interleukin-10 secretion. The present study investigated the possible association between interleukin-10 gene polymorphism and periodontal disease progression. MATERIAL AND METHODS Genomic DNA was obtained from 252 adults who were part of a prospective longitudinal study on the progression of periodontal disease in a general adult Australian population. Single nucleotide polymorphisms at positions -592 and -1082 in the interleukin-10 promoter were analysed using an induced heteroduplex methodology and used to determine interleukin-10 promoter haplotypes in individual samples. Periodontitis progression was assessed by measuring probing depths and relative attachment levels at regular intervals over a 5-year period. A generalized linear model was used to analyse the data, with age, gender, smoking status, interleukin-1 genotype and Porphyromonas gingivalis included as possible confounders. RESULTS There was a significant (p approximately 0.02) main effect of interleukin-10 haplotypes, with individuals having either the ATA/ACC or the ACC/ACC genotype experiencing around 20% fewer probing depths of >or= 4 mm compared to individuals with other genotypes. Age and smoking had significant (p < 0.001) additional effects. CONCLUSION These data suggest that the interleukin-10 genotype contributes to the progression of periodontal disease.

Is there a role for triclosan/copolymer toothpaste in the management of periodontal disease?

Dental caries and periodontal disease are the most common oral conditions experienced by adults today. The treatment of these diseases by the dental team can only be performed when patients attend dental practices. There is recognition that the preventive measures patients perform at home between dental visits is of vital importance in the control of these diseases. Water fluoridation and fluoridated toothpastes have made enormous progress into the prevention of dental caries worldwide. However, prevention of periodontal disease is yet to enjoy the same success. A number of toothpastes have been developed for the prevention and control of periodontal disease. One such toothpaste – containing triclosan/copolymer - has been thoroughly researched. The literature pertaining to the efficacy, mode of action and safety of triclosan/copolymer toothpaste has been reviewed. A MEDLINE search identified 198 articles dated from 1989 to 2008. The findings of this body of research are discussed and conclusions regarding the efficacy of triclosan/copolymer toothpaste in the home-care management of periodontal disease are presented.

Risk factors that may modify the innate and adaptive immune responses in periodontal diseases

Plaque-induced periodontal diseases occur in response to the accumulation of dental plaque. Disease manifestation and progression is determined by the nature of the immune response to the bacterial complexes in plaque. In general, predisposing factors for these periodontal diseases can be defined as those factors which retain or hinder the removal of plaque and, depending upon the nature of the immune response to this plaque, the disease will either remain stable and not progress or it may progress and result in chronic periodontitis. In contrast, modifying factors can be defined as those factors that alter the nature or course of the inflammatory lesion. These factors do not cause the disease but rather modify the chronic inflammatory response, which, in turn, is determined by the nature of the innate and adaptive immune responses and the local cytokine and inflammatory mediator networks. Chronic inflammation is characterized by vascular, cellular and repair responses within the tissues. This paper will focus on how common modifying factors, such as smoking, stress, hormonal changes, diabetes, metabolic syndrome and HIV/AIDS, influence each of these responses, together with treatment implications. As treatment planning in periodontics requires an understanding of the etiology and pathogenesis of the disease, it is important for all modifying factors to be taken into account. For some of these, such as smoking, stress and diabetic control, supportive health behavior advice within the dental setting should be an integral component for overall patient management.

Long term use of triclosan toothpaste and thyroid function

The long term effects of usage of triclosan-containing toothpaste on thyroid function are currently unknown. Triclosan is structurally similar to thyroid hormones and reductions in serum thyroid hormone levels have been observed in animal studies following oral administration of triclosan. Therefore, an assessment of thyroid function over 4 years was undertaken in a subset of individuals in a randomised, placebo controlled clinical trial comparing the effects of 0.3% triclosan toothpaste with placebo toothpaste in subjects with coronary heart disease. Thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), antithyroglobulin antibody (anti-TGab) and antithyroid peroxidase antibody (TPOab) were measured. Paired serum samples at year 1 and year 5 from 132 subjects (64 triclosan group, 68 placebo group) were analysed. At year 1 there were no significant differences in thyroid function between the groups: mean (SD) TSH 1.4 (0.8) and 1.6 (0.9) mU/L, triclosan and placebo groups respectively, fT4 15.8 (2.2) and 15.2 (2.1) pmol/L; fT3 4.8 (0.5) and 4.8 (0.5) pmol/L. Similarly, for antithyroid antibodies there were no group differences at year 1. Median (25th, 75th percentile) for anti-TGab, 38 (34, 42) and 37 (30, 42) U/mL triclosan and placebo groups respectively; anti-TPOab, 15 (10, 22) and 18 (10, 24) U/mL. At year 5, fT4 was the only measure to show a significant difference between groups (mean and 95% Confidence Interval) 15.6 (15.1, 16.1) and 14.7 (14.2, 15.1) pmol/L triclosan and placebo respectively (p=0.01). This reflects reduced levels in the placebo group but no change in the triclosan group. In conclusion, over 4 years triclosan toothpaste had no detectable effect on thyroid function. The data support the view that 0.3% triclosan in toothpaste is safe and free of significant thyroid adverse effects.