Periodontal diagnosis in the context of the 2017 classification system of periodontal diseases and conditions: presentation of a patient with periodontitis localised to the molar teeth.

The objective of this case report is to illustrate the diagnosis and classification of periodontitis, according to the 2017 classification system, as recommended in the British Society of Periodontology (BSP) implementation plan. A 37-year-old female was diagnosed with periodontitis (molar-incisor pattern), stage III, grade C, currently unstable. Several issues pertinent to the diagnosis of localised forms of periodontitis in young patients are discussed in relation to the current and previous classification systems. Periodontitis can be limited to a few sites and this case highlights the importance of the careful application of the basic periodontal examination (BPE).

Periodontal diagnosis in the context of the 2017 classification system of periodontal diseases and conditions: Presentation of a middle-aged patient with localised periodontitis.

The objective of this case report is to illustrate the diagnosis and classification of periodontitis according to the 2017 classification system as recommended in the British Society of Periodontology (BSP) implementation plan. We describe a case of a patient who was diagnosed with 'localised periodontitis; stage II, grade B; currently unstable'. The present case report presents an example for the application of the new classification system and illustrates how the new classification system captures disease severity, extent and disease susceptibility by staging and grading periodontitis.

Periodontal diagnosis in the context of the 2017 classification system of periodontal diseases and conditions - implementation in clinical practice.

The 2017 World Workshop Classification system for periodontal and peri-implant diseases and conditions was developed in order to accommodate advances in knowledge derived from both biological and clinical research, that have emerged since the 1999 International Classification of Periodontal Diseases. Importantly, it defines clinical health for the first time, and distinguishes an intact and a reduced periodontium throughout. The term 'aggressive periodontitis' was removed, creating a staging and grading system for periodontitis that is based primarily upon attachment and bone loss and classifies the disease into four stages based on severity (I, II, III or IV) and three grades based on disease susceptibility (A, B or C). The British Society of Periodontology (BSP) convened an implementation group to develop guidance on how the new classification system should be implemented in clinical practice. A particular focus was to describe how the new classification system integrates with established diagnostic parameters and pathways, such as the basic periodontal examination (BPE). This implementation plan focuses on clinical practice; for research, readers are advised to follow the international classification system. In this paper we describe a diagnostic pathway for plaque-induced periodontal diseases that is consistent with established guidance and accommodates the novel 2017 classification system, as recommended by the BSP implementation group. Subsequent case reports will provide examples of the application of this guidance in clinical practice.

Periodontal diagnosis in the context of the BSP implementation plan for the 2017 classification system of periodontal diseases and conditions: presentation of a pair of young siblings with periodontitis.

The objective of this case report is to illustrate the diagnosis and classification of periodontitis according to the 2017 classification system as recommended in the British Society of Periodontology (BSP) implementation plan. We describe two cases in the form of a pair of siblings, who developed periodontitis very early in life. A 19-year-old female was diagnosed with 'generalised periodontitis; stage III/grade C; currently unstable'. Her 14-year-old sister was diagnosed with 'localised periodontitis; stage II, grade C; currently unstable'. The present case report presents an example for the application of the new classification system and illustrates the importance of a periodontal check for children and adolescents and/or their relatives.

Comparative analysis of immune cell subsets in peripheral blood from patients with periodontal disease and healthy controls.

Periodontitis is a chronic inflammatory disease caused by the colonization of teeth by the bacterial plaque biofilm and the resultant host immune responses in adjacent periodontal tissues. Disease severity can vary dramatically between patients with periodontitis, with some subjects displaying inflammation without bony destruction (gingivitis), while others experience chronic progressive or rapidly aggressive gingival connective tissue damage and bone loss. To determine whether peripheral immune dysregulation is associated with periodontitis, we performed extensive analysis of immune cell subsets in peripheral blood from patients with chronic or aggressive periodontitis versus periodontally healthy control subjects. Peripheral blood mononuclear cells (PBMC) from patients with chronic periodontitis or aggressive periodontitis and from periodontally healthy controls were analysed by 8-10-colour flow cytometry for the frequencies of various lymphocyte subsets, including interleukin (IL)-17-, interferon (IFN)-γ-, tumour necrosis factor (TNF)-α- and IL-10-producing cells, and the frequencies and phenotype of monocytes. Cytokine levels in serum from the different groups were determined by Luminex assay. We found no significant differences in the frequencies of major immune cell populations [CD4+ T cells, CD8+ T cells, γδ T cells, CD4+ CD45RO+ CD25+ CD127low regulatory T cells (Tregs ), CD19+ B cells, CD14+ monocytes] or of cytokine-producing T cells, or in the phenotype of CD14+ monocytes in peripheral blood from these patient cohorts. Additionally, no significant differences were observed in serum levels of prototypical inflammatory cytokines. These results suggest that the local gingival inflammatory response is not reflected by obvious changes in major blood immune cell subset frequencies.

Drugs, medications and periodontal disease.

This paper reviews the effects that drugs may have on the gingival and periodontal tissues. Drug-induced gingival overgrowth has been recognised for over 70 years but is becoming a more prevalent occurrence with wider use of antihypertensive and immunosuppressant drugs. The anti-inflammatory steroids, non-steroidal drugs and anti-TNF-α agents might all be expected to exert a dampening effect on chronic periodontitis although the evidence is somewhat equivocal and none of these drugs has emerged as potentially valuable adjuncts to treat periodontal disease. Desquamative gingivitis is a clinical appearance of aggressive gingival inflammation with which a number of drugs have been associated and the oral contraceptives have also been implicated in the development of gingival inflammation. Patients who are prescribed bisphosphonates and anti-platelet drugs are at risk of serious side effects following more invasive dental procedures including extractions and surgical treatments although timely, conventional management of periodontal disease may be undertaken to reduce periodontal inflammation, prevent disease progression and ultimately the need for extractions.

Diabetes and periodontal disease: a two-way relationship.

Periodontitis and diabetes are common, complex, chronic diseases with an established bidirectional relationship. That is, diabetes (particularly if glycaemic control is poor) is associated with an increased prevalence and severity of periodontitis, and, severe periodontitis is associated with compromised glycaemic control. Periodontal treatment (conventional non-surgical periodontal therapy) has been associated with improvements in glycaemic control in diabetic patients, with reductions in HbA1c of approximately 0.4% following periodontal therapy. For these reasons, management of periodontitis in people with diabetes is particularly important. The dental team therefore has an important role to play in the management of people with diabetes. An emerging role for dental professionals is envisaged, in which diabetes screening tools could be used to identify patients at high risk of diabetes, to enable them to seek further investigation and assessment from medical healthcare providers.

Treatment outcome following use of the erbium, chromium:yttrium, scandium, gallium, garnet laser in the non-surgical management of peri-implantitis: a case series.

AIM: To date there is no consensus on the appropriate usage of lasers in the management of peri-implantitis. Our aim was to conduct a retrospective clinical analysis of a case series of implants treated using an erbium, chromium:yttrium, scandium, gallium, garnet laser. MATERIALS AND METHODS: Twenty-eight implants with peri-implantitis in 11 patients were treated with an Er,Cr:YSGG laser (68 sites >4 mm), using a 14 mm, 500 µm diameter, 60° (85%) radial firing tip (1.5 W, 30 Hz, short (140 µs) pulse, 50 mJ/pulse, 50% water, 40% air). Probing depths were recorded at baseline after 2 months and 6 months, along with the presence of bleeding on probing. RESULTS: The age range was 27-69 years (mean 55.9); mean pocket depth at baseline was 6.64 ± SD 1.48 mm (range 5-12 mm),with a mean residual depth of 3.29 ± 1.02 mm (range 1-6 mm) after 2 months, and 2.97 ± 0.7 mm (range 1-9 mm) at 6 months. Reductions from baseline to both 2 and 6 months were highly statistically significant (P <0.001). Patient level reduction in bleeding from baseline to both 2 and 6 months were statistically significant (P <0.001). CONCLUSION: In view of the positive findings in this pilot study, well-designed randomised controlled trials of the use of Er,Cr:YSGG laser in the non-surgical management of peri-implantitis are required to validate our clinical findings.

The prevalence of periodontal disease in a Romano-British population c. 200-400 AD.

OBJECTIVE: The aim of this study was to investigate the prevalence of moderate to severe periodontitis in an ancient British cohort c. 200-400 AD. DESIGN: Observational study to assess periodontal and other oral disease parameters. SETTING: Natural History Museum, London. SUBJECTS AND METHODS: 303 skulls from a Romano-British burial site in Poundbury, Dorset were examined for evidence of dental disease. MAIN OUTCOME MEASURES: The primary outcome measure was presence of moderate to severe periodontitis. Secondary outcomes included: amount of horizontal bone loss; prevalence of ante-mortem tooth loss; and presence of other dental pathologies. RESULTS: The overall prevalence of moderate to severe periodontitis was just greater than 5%. The prevalence rate remained nearly constant between ages 20 to 60, after which it rose to around 10%. The number of affected teeth increased with age. Horizontal bone loss was generally minor. Caries was seen in around 50% of the cohort, and evidence of pulpal and apical pathology was seen in around 25%. CONCLUSIONS: The prevalence of moderate to severe periodontitis was markedly decreased when compared to the prevalence in modern populations, underlining the potential importance of risk factors such as smoking and diabetes in determining susceptibility to progressive periodontitis in modern populations.

Effects of low-dose doxycycline on cytokine secretion in human monocytes stimulated with Aggregatibacter actinomycetemcomitans.

Doxycycline is an antibiotic used in the treatment of a variety of inflammatory conditions, including periodontitis. Apart from its antimicrobial properties, this drug also has independent anti-inflammatory effects at sub-antimicrobial doses. The present study aimed to investigate the effects of low-doses of doxycycline (LDD) on cytokine production by human monocytic cells challenged with the periodontal pathogen Aggregatibacter actinomycetemcomitans, for up to 6 h. The simultaneous regulation of 12 cytokines were measured by a Human Cytokine Array Kit. To validate the array findings, selected cytokines were also measured by enzyme-linked immunosorbant assay (ELISA). A. actinomycetemcomitans stimulated the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1ß, IL-6 and IL-8 by the cells after 6 h of challenge, and doxycycline significantly inhibited this effect. The kinetics of this regulation demonstrated an early (within 2 h) and significant (P<0.05) inhibition of pro-inflammatory cytokines, with a mild (0.5-fold) up-regulation of the anti-inflammatory cytokine IL-10. The results indicate that LDD acts as an anti-inflammatory agent in human monocytic cells stimulated with A. actinomycetemcomitans. This model provides clear evidence that some of the clinically proven benefits of LDD may be related to its ability to regulate inflammatory mediator release by monocytic cells. This property may contribute to the clinically proven benefits of this antibiotic as an adjunctive treatment for periodontitis.

Involvement of autoimmunity in the pathogenesis of aggressive periodontitis.

The aim of this study was to investigate the involvement of autoimmune reactions to native and post-translationally modified extracellular matrix components in the pathogenesis of periodontitis. Sera from individuals with aggressive periodontitis (AgP, n = 25), chronic periodontitis (CP, n = 14), and gingivitis (G, n = 18) were tested for the presence of autoantibodies against: (a) native collagen type I (CI) and collagen type III (CIII); (b) CI and CIII post-translationally modified by reactive oxygen species (ROS) of the type present during inflammation; and (c) citrullinated filaggrin-derived peptides (CCP). Autoantibodies to native and ROS-modified CI and CIII as well as autoantibodies to CCP were observed exclusively in patients with AgP and not in those with CP or G. In conclusion, autoimmune reactions to native and post-translationally modified self-antigens may play a role specifically in the pathogenesis of AgP.

Periodontal regeneration: a challenge for the tissue engineer?

Periodontitis affects around 15 per cent of human adult populations. While periodontal treatment aimed at removing the bacterial cause of the disease is generally very successful, the ability predictably to regenerate the damaged tissues remains a major unmet objective for new treatment strategies. Existing treatments include the use of space-maintaining barrier membranes (guided tissue regeneration), use of graft materials, and application of bioactive molecules to induce regeneration, but their overall effects are relatively modest and restricted in application. The periodontal ligament is rich in mesenchymal stem cells, and the understanding of the signalling molecules that may regulate their differentation has increased enormously in recent years. Applying these principles for the development of new tissue engineering strategies for periodontal regeneration will require further work to determine the efficacy of current experimental preclinical treatments, including pharmacological application of growth factors such as bone morphogenetic proteins (BMPs) or Wnts, use of autologous stem cell reimplantation strategies, and development of improved biomaterial scaffolds. This article describes the background to this problem, addresses the current status of periodontal regeneration, including the background biology, and discusses the potential for some of these experimental therapies to achieve the goal of clinically predictable periodontal regeneration.

Ovariectomy vs. hypofunction: their effects on rat mandibular bone.

Previous studies have suggested that the mandible may be more influenced by mechanical loading than by circulating hormone levels. We tested the hypothesis that hypofunction has a greater influence than ovariectomy on mandibular bone. Two-month-old rats were ovariectomized (OVX) or had maxillary molars removed from one side to induce unilateral mandibular hypofunction. Control animals remained untreated. After 5 months, animals were killed, and bones were assessed by micro-tomography (muCT), quantitative back-scattered electron analysis in an SEM (qBSE-SEM), and light microscopy. Mineralization density was reduced in calvarial, maxillary, and mandibular alveolar bone following OVX, yet was increased in lingual mandibular alveolar bone of the hypo-function animals compared with controls. OVX caused a reduction in osteocyte density in alveolar bone, while hypofunction showed an increase compared with controls. Hypofunction led to alveolar bone becoming more highly mineralized and more cellular, while ovariectomy caused a reduction in both mineralization density and osteocyte numbers.

Absorption and release of protein from hydroxyapatite-polylactic acid (HA-PLA) membranes.

OBJECTIVES: The aim of this study was to investigate the kinetics of protein interactions with a novel hydroxyapatite-polylactide (HA-PLA) composite membrane material. METHODS: Trilayer PLA and HA-PLA composite membranes reinforced with PLA fibres were used to absorb and release protein which was measured by a BioRad assay. The proteins used were fetal calf serum and bovine serum albumin. PLA and HA-PLA composite films were manufactured to test permeability. RESULTS: Maximal protein absorption was seen within 5min of treating materials; a nearly 8-fold increase in total absorption was seen with HA-containing composites compared to those without HA. These also exhibited a more gradual and sustained release of protein for periods of up to 96h, for example at 24h protein concentrations released were 2.20+/-2.80 and 0.49+/-5.38microg/ml for membranes with and without HA respectively. In addition low pressure and temperature used during production of membranes also allowed greater and more sustained protein release. HA-PLA composite films also showed marked increased permeability compared to plain PLA films, for example after 24h PLA only films 3.64+/-1.01microg/ml, PLA film with 25% HA: 44.99+/-35.61microg/ml, PLA film with 75% HA: 153.12+/-65.57microg/ml. CONCLUSIONS: The results demonstrate that these composite membranes rapidly absorb protein and that the absorbed protein is released slowly for periods of up to 96h, dependent on constituents of the material and the manufacturing conditions. Incorporation of HA into these membranes was the key factor for improved protein kinetics and membrane permeability.

Tumor necrosis factor-alpha-converting enzyme (TACE) levels in periodontal diseases.

Tumor necrosis factor-alpha-converting enzyme (TACE) is a metalloprotease which can shed several cytokines from the cell membrane, including receptor activator of NF-kappaB ligand (RANKL). This study aimed to investigate the hypothesis that TACE would be elevated in the gingival crevicular fluid (GCF) of persons with periodontitis. Total TACE amounts in GCF were higher in persons with chronic and aggressive periodontitis than in those with gingivitis or in healthy persons. TACE concentrations in GCF were higher in persons with chronic and aggressive periodontitis than in those with gingivitis, although not significantly higher than in healthy persons. Persons with chronic periodontitis receiving immunosuppressive treatment exhibited over 10-fold lower TACE levels than the other periodontitis groups. TACE was positively correlated with probing pocket depth, clinical attachment levels, and RANKL concentrations in GCF. In conclusion, the increased GCF TACE levels in persons with periodontitis and their positive correlation with RANKL may indicate an association of this enzyme with alveolar bone loss, and may warrant special attention in future therapeutic approaches.

Porphyromonas gingivalis antagonises Campylobacter rectus induced cytokine production by human monocytes.

Porphyromonas gingivalis and Campylobacter rectus are two major bacterial species implicated in the pathogenesis of periodontitis. P. gingivalis can antagonise the inflammatory response to other periodontal pathogens, a property commonly attributed to its lipopolysaccharide (LPS). The aim of this study was to investigate the capacity of P. gingivalis to antagonise C. rectus induced cytokine stimulation from human monocytes, and to investigate the involvement of its LPS. Primary human monocytes and Monomac-6 cells were challenged with culture supernatants from P. gingivalis and C. rectus, and levels of IL-1beta, IL-6 and IL-8 produced were measured by ELISA after 6h incubation. Purified P. gingivalis LPS was also added alone or in combination with C. rectus culture supernatant. Both species significantly stimulated the production of all three cytokines from the two cell lines, but P. gingivalis was considerably weaker inducer. Co-stimulation of the cells with P. gingivalis and C. rectus suppressed the cytokine-stimulatory capacity of the latter. P. gingivalis LPS alone was sufficient to antagonise IL-6 and IL-8, but not IL-1beta stimulation by C. rectus. In conclusion, mixed infections may impair host immune responses by reducing pro-inflammatory cytokine levels, which may be of relevance to the pathogenesis of periodontitis.

Differential expression of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin mRNA in periodontal diseases.

BACKGROUND AND OBJECTIVE: Receptor activator of nuclear factor-kappaB ligand (RANKL) is responsible for the induction of osteoclastogenesis and bone resorption, whereas its decoy receptor, osteoprotegerin, can directly block this action. Because this dyad of cytokines is crucial for regulating the bone remodelling process, imbalances in their expression may cause a switch from the physiological state to enhanced bone resorption or formation. This study investigated the mRNA expression of RANKL and osteoprotegerin, as well as their relative ratio, in the gingival tissues of patients with various forms of periodontal diseases. MATERIAL AND METHODS: Gingival tissue was obtained from nine healthy subjects and 41 patients, who had gingivitis, chronic periodontitis, generalized aggressive periodontitis, and chronic periodontitis and were receiving immunosuppressant therapy. Quantitative real-time polymerase chain reaction was employed to evaluate the mRNA expression of RANKL and osteoprotegerin in these tissues. RESULTS: Compared with healthy individuals, patients in all periodontitis groups, but not those with gingivitis, exhibited stronger RANKL expression and a higher relative RANKL/osteoprotegerin ratio. In addition, osteoprotegerin expression was weaker in patients with chronic periodontitis. When patients with generalized aggressive periodontitis and chronic periodontitis were compared, the former exhibited stronger RANKL expression, whereas the latter exhibited weaker osteoprotegerin expression, and there was no difference in their relative ratio. When chronic periodontitis patients were compared with chronic periodontitis patients receiving immunosuppressant therapy, osteoprotegerin, but not RANKL, expression was stronger in the latter. CONCLUSION: This study demonstrates that RANKL and osteoprotegerin expression are differentially regulated in various forms of periodontitis, and the relative RANKL/osteoprotegerin ratio appears to be indicative of disease occurrence. This information may confer diagnostic and therapeutic value in periodontitis.

Interleukin-1alpha stimulation in monocytes by periodontal bacteria: antagonistic effects of Porphyromonas gingivalis.

Periodontal pathogenic bacteria are associated with elevated levels of interleukin-1alpha (IL-1alpha) but it is unclear if all species can induce cytokine production equally. Porphyromonas gingivalis may be able antagonize IL-1alpha induced by other species through the activity of its proteases or lipopolysaccharide (LPS). Monomac-6 cells and primary human monocytes were treated with culture supernatants from Porphyromonas gingivalis, Fusobacterium nucleatum, Campylobacter rectus, Actinobacillus actinomycetemcomitans, Prevotella intermedius, Veillonella atypical and Prevotella nigrescens. IL-1alpha protein levels were measured after 6 h of incubation. In addition, monocytes were co-stimulated with supernatants from P. gingivalis and other bacteria. The role of P. gingivalis proteases was tested using Arg-X and Lys-X mutant strains. The role of LPS was investigated using purified P. gingivalis LPS and polymixin depletion. All species tested induced significant IL-1alpha production, but P. gingivalis was the weakest. Co-stimulation of monocytes with P. gingivalis antagonized the ability of other bacterial species to induce IL-1alpha production. This effect was at its greatest with C. rectus (resulting in a 70% reduction). Gingipain mutant strains and chemical inhibition of protease activity did not reduce antagonistic activity. However, 100 ng/ml of P. gingivalis LPS can reproduce the antagonistic activity of P. gingivalis culture supernatants. Periodontitis-associated bacterial species stimulate IL-1alpha production by monocytes. P. gingivalis can antagonize this effect, and its LPS appears to be the crucial component. This study highlights the importance of mixed infections in the pathogenesis of periodontal disease because reduction of pro-inflammatory cytokine levels may impair the ability of the host to tackle infection.

Measurement of both native and inactivated forms of alpha1 proteinase inhibitor in human inflammatory extracellular fluids.

BACKGROUND: Inactivation of the elastase inhibitor, alpha1 proteinase inhibitor (alpha1PI), may be of pathogenic significance in inflammatory diseases like periodontal disease. Two key mechanisms of inactivation appear to be (a) the formation of an alpha1PI-elastase complex and (b) proteolytic cleavage by elastase or other enzymes such as metalloproteinases of host origin or enzymes of bacterial origin. Based on the different heat stabilities of the intact, complexed and proteolytically cleaved forms of alpha1PI, an enzyme-linked immunosorbent assay (ELISA) that allowed the simultaneous measurement of native and inactive forms of alpha1PI was developed. METHODS: The ELISA method described employs a commercially available antibody and represents a rapid, reproducible and sensitive method for studying alpha1PI inactivation in human inflammatory diseases. The assay was applied to normal human plasma and to human extracellular fluids obtained from patients with inflammatory diseases such as adult periodontitis and rheumatoid arthritis. Samples from patients with osteoarthritis, a "non-inflammatory" joint disease, were also studied. RESULTS: The findings expressed as the mean percentage (+/-SD) of the total alpha1PI that was inactivated were as follows: gingival crevicular fluid from adult periodontitis patients: 73.5+/-16.6% (n=12); normal human plasma: 8.4+/-4.9% (n=13); knee-joint synovial fluid (SF) from rheumatoid arthritis patients: 12.5+/-4.5% (n=15); plasma from rheumatoid arthritis patients: 8.0+/-1.8% (n=15); knee-joint SF from osteoarthritis patients: 8.6+/-8.2% (n=14); plasma from osteoarthritis patients: 5.7+/-4.8% (n=14). The results obtained by ELISA were in good agreement with those obtained by the semi-quantitative method of SDS-PAGE and Western blotting. CONCLUSIONS: We have shown that the differential heat stability of alpha1PI may be utilised as the basis for a rapid, sensitive and reproducible ELISA assay of alpha1PI inactivation. In gingival crevicular fluid from periodontal disease patients, alpha1PI is mainly inactivated and the extent of this inactivation is much higher than in inflammatory fluids from other chronic diseases such as rheumatoid arthritis. This assay could be useful in monitoring the progression of periodontal disease.

Release of recombinant human bone morphogenetic protein-2 from heterocyclic methacrylate polymer systems.

The release of recombinant human bone morphogenetic protein-2 (rhBMP-2) from three room temperature polymerising methacrylate systems has been studied. These all contained poly(ethyl methacrylate) powder, but the monomer liquids comprised, respectively, tetrahydrofurfuryl methacrylate (THFM), 90/10 THFM/hydroxyethyl methacrylate (HEMA), and 70/30 THFM/ HEMA. In all cases, rhBMP-2 was released, but the addition of 10% HEMA accelerated release (a nine-fold increase in diffusion coefficient); a further increase to 30% HEMA had no additional effect. For most of the release process, a diffusion process operated, although the early stages were not well defined. At the end of the 15 day period, the release, respectively, for the PEM/THFM, PEM:90/10 THFM/HEMA and PEM:70/30 THFM/HEMA systems was 596, 878 and 923 ng (i.e. up to 92% of the rhBMP-2 added).