Interactions between chronic renal disease and periodontal disease

The incidence of end-stage renal disease (ESRD) is increasing and patients receiving renal replacement therapy including hemodialysis, peritoneal dialysis or renal transplantation will comprise an enlarging segment of the dental patient population. Renal replacement therapy can affect periodontal tissues including gingival hyperplasia in immune suppressed renal transplantation patients and increased levels of plaque, calculus and gingival inflammation and possible increased prevalence and severity of destructive periodontal diseases in ESRD patients on dialysis maintenance therapy. Also, the presence of undiagnosed periodontitis may have significant effects on the medical management of the ESRD patient. Periodontitis has been found to contribute to systemic inflammatory burden including the elevation of C-reactive protein (CRP) in the general population. Atherosclerotic complications including myocardial infarction and stroke are the primary causes of mortality in the ESRD population and, in contrast to that of the general population, the best predictor of all cause and cardiac death in this population is CRP. Consequently, periodontitis may be a covert but treatable source of systemic inflammation in the ESRD population. The objective of this review was to explore the interaction between chronic renal disease, renal replacement therapy and periodontal diseases based upon the results of studies published within the last decade.     

Periodontitis modified by systemic factors

Microbial dental plaque is the initiator of periodontal disease but whether it affects a particular subject, what form the disease takes, and how it progresses, are all dependent on the host defenses to this challenge. Systemic factors modify all forms periodontitis principally through their effects on the normal immune and inflammatory defenses. Some good examples of this effect exist such as when there is a reduction in number or function of polymorphonuclear leukocytes (PMNs) that may result in an increased rate and severity of periodontal destruction. Many other systemic factors are much less clear cut and are difficult to causally link to periodontitis. In many cases the literature is insufficient to make definite statements on links between systemic factors and periodontitis. It is also at times difficult to be precise regarding the causative agent in systemic exposures such as smoking and even prescribed drug therapy. The possible role of systemic diseases and systemic exposures in initiating or modifying the progress of periodontal disease is clearly a complex issue. It is however generally agreed that several conditions may give rise to an increased prevalence, incidence, or severity of gingivitis and periodontitis. The categorization of the systemic modifying factors causing periodontitis and the evidence to support the role of these factors are the focus of this review. An attempt has been made to consider the conditions under broad headings, but it will be clear that many conditions fall within more than one category and that for several conditions only case reports exist whereas in other areas an extensive literature is present.     

Cardiovascular disease and periodontitis: an update on the associations and risk

Background: Associations between periodontitis and cardiovascular diseases have been recognized.
Material and Methods: New literature since the last European Workshop on Periodontology has been reviewed.
Results: The lack of reliable epidemiological data on disease prevalence makes an assessment of the associations and risks between periodontitis and cardiovascular diseases difficult. Two recent meta-analysis reports have identified associations between periodontitis and cardiovascular diseases (odds ratios: 1.1–2.2). Different surrogate markers for both disease entities, including serum biomarkers, have been investigated. Brachial artery flow-mediated dilatation, and carotid intima media thickness have in some studies been linked to periodontitis. Studies are needed to confirm early results of improvements of such surrogate markers following periodontal therapy. While intensive periodontal therapy may enhance inflammatory responses and impair vascular functions, studies are needed to assess the outcome of periodontal therapies in subjects with confirmed cardiovascular conditions. Tooth eradication may also reduce the systemic inflammatory burden of individuals with severe periodontitis. The role of confounders remain unclear.
Conclusions: Periodontitis may contribute to cardiovascular disease and stroke in susceptible subjects. Properly powered longitudinal case–control and intervention trials are needed to identify how periodontitis and periodontal interventions may have an impact on cardiovascular diseases.     

Diabetes and periodontal disease: an example of an oral/systemic relationship

Periodontal disease has been identified as a major complication of diabetes mellitus. Diabetics experience increased destruction of periodontal tissues as a result of an abnormal immune response, altered fibroblast function and levels of collagen, as well as the microvascular effects of advanced glycosylation end products (AGE). The accumulation of AGE in the periodontium is correlated with an increase in the level of inflammatory mediators, which are associated with tissue destruction. These inflammatory mediators may contribute to the severity of tissue destruction in diabetics with periodontal disease. The increased prevalence of periodontal disease in diabetics is an example of an oral/systemic relationship. There is evidence that this relationship may be two-dimensional as well, as diabetics with active periodontitis tend to have poor glycemic control when compared to patients without periodontitis.     

The role of inflammatory and immunological mediators in periodontitis and cardiovascular disease

Epidemiological studies have implicated periodontitis (PD) as a risk factor for development of cardiovascular disease (CVD). Persistent infections such as periodontitis induce inflammatory and immune responses which may contribute to coronary atherogenesis, and, in conjunction with other risk factors, may lead to coronary heart disease (CHD). In this review, mechanisms are described that may help explain the association between periodontal infections and CHD. Periodontal diseases are bacterial infections associated with bacteremia, inflammation, and a strong immune response, all of which may represent significant risk factors for the development of atherogenesis, CHD, and myocardial infarction (MI). Several mechanisms may participate in this association, including those induced by oral organisms, and those associated with host response factors. This review will focus on host factors. Oral pathogens and inflammatory mediators (such as interleukin [IL]-1 and tumor necrosis factor [TNF]-alpha) from periodontal lesions intermittently reach the bloodstream inducing systemic inflammatory reactants such as acute-phase proteins, and immune effectors including systemic antibodies to periodontal bacteria. This review will describe the potential role of various inflammatory as well as immunologic factors that may play a role in periodontitis as a possible risk factor for CHD.     

具核梭杆菌与牙周炎关系的研究进展

牙周炎是由多种微生物引起的感染性疾病。具核梭杆菌在牙周炎中有高检出率,两者有强相关性。具核梭杆菌可借助多种黏附素共聚致病菌、黏附侵入上皮细胞,利用毒力因子和代谢产物等破坏牙周组织,并可诱导宿主产生免疫反应,促进牙周疾病甚至全身系统性疾病的发生发展。但目前临床上辅助牙周基础治疗的药物并不能针对具核梭杆菌等特定牙周致病菌,可能会导致菌群失调或耐药等问题。具核梭杆菌致病机制的研究为牙周炎的预防及治疗提供了新的思路,研发针对具核梭杆菌黏附素、毒力因子、代谢产物或切断各个致病通路的材料、药物、益生菌产品,抑制其在深牙周袋中的增殖和炎症反应,保持与其他口腔微生物及宿主的动态平衡,有利于牙周炎的控制。     

内质网应激在牙周炎影响全身疾病过程 中的作用

牙周炎是发生在牙周组织的慢性感染性疾病,其发病机制及对全身系统疾病的影响一直是学术界关注的热点问题。许多学者认为,牙周炎不仅是一种常见的口腔疾病,更是全身疾病的潜在危险因素之一,但是目前关于牙周炎诱发全身系统疾病的具体机制尚不明确,可能与牙周致病菌、炎症因子及内质网应激等有关。近年来的研究发现,内质网应激是介导细胞凋亡的重要通路之一,并且与全身疾病密切相关。有研究显示,内质网应激在牙周炎诱导全身疾病过程中存在调控作用,但是目前关于内质网应激在牙周炎影响全身疾病过程中的作用研究较少,需要进一步探索。本文就内质网应激在牙周炎影响全身系统疾病中的研究进展进行综述,旨在探究牙周炎和全身系统疾病的内在联系,以期为牙周炎与其相关全身系统疾病的防治提供新的思路。     

牙周炎和前列腺疾病相关性研究现状

牙周炎是常见的口腔炎症性疾病,有大量文献报告牙周炎与全身系统性疾病存在密切联系,如心血管疾病、2型糖尿病、早产低出生体重儿等.牙周炎与前列腺疾病有相似的风险因素,年龄、吸烟、肥胖和糖尿病以及炎症的刺激对疾病有显著影响.该文主要对牙周炎和前列腺疾病的相关性的研究情况,共同的影响因素,以及相关的生物学机制等进行综述.     

Periodontal diseases and association with atherosclerotic disease

Cardiovascular diseases still account for the majority of deaths worldwide, although significant improvements in survival, after being affected by cardiovascular disease, have been achieved in the last decades. Periodontal diseases are also a common global burden. Several studies have shown a link between cardiovascular disease and periodontitis, although evidence is still lacking regarding the direct cause-effect relation. During the 2012 “Periodontitis and systemic diseases” workshop, the available evidence on the association between cardiovascular and periodontal diseases was discussed, covering biologic plausibility and clinical studies. The objective of the present narrative review was to update the previous reviews presented at the 2012 workshop, following similar methodological approaches, aiming to critically assess the available evidence. With regard to biologic plausibility, two aspects were reviewed: (a) for microbiologic mechanisms, assessing periodontal bacteria as a contributing factor to atherosclerosis based on seven “proofs,” substantial evidence was found for Proofs 1 through 6, but not for Proof 7 (periodontal bacteria obtained from human atheromas can cause atherosclerosis in animal models), concluding that periodontal pathogens can contribute to atherosclerosis; (b) mechanistic studies, addressing five different inflammatory pathways that could explain the links between periodontitis and cardiovascular disease with the addition of some extra pathways , suggest an association between both entities, based on the presence of higher levels of these inflammatory markers in patients with periodontitis and cardiovascular disease, vs healthy controls, as well as on the evidence that periodontal treatment reduces serum levels of these mediators. When evidence from clinical studies was analyzed, two aspects were covered: (a) epidemiologic studies support the estimation that the incidence of atherosclerotic disease is higher in individuals with periodontitis than in individuals with no reported periodontitis, irrespective of many common risk factors, but with a substantial variability in the definitions used in reporting of exposure to periodontal diseases in different studies; (b) intervention trials have shown that periodontal therapy can reduce serum inflammatory mediators, improve the lipids profile, and induce positive changes in other cardiovascular disease surrogate measures, but no evidence is available to support that adequate periodontal therapy is able to reduce the risk for cardiovascular diseases, or the incidence of cardiovascular disease events in periodontitis patients.     

牙周炎与高血压关系的研究进展

高血压是与遗传和环境因素有关的最常见的一种心血管疾病。牙周炎是发生在牙齿支持组织(牙龈、牙周膜、牙槽骨)的一种破坏性疾病。研究表明:高血压与牙周炎之间相互关联,牙周炎增加高血压病的患病率,高血压亦增加牙周炎的发病风险和严重程度。但是,两者相互作用的机制尚未完全明确,炎症可能是2种疾病的中介,共同的危险因素促进2种疾病的同时发生发展。本文主要就牙周炎与高血压相关性及其相互作用机制进行综述。     

Changing periodontal paradigms: therapeutic implications

Many paradigms concerning the epidemiology, pathogenesis, and systemic impact of periodontal diseases have been modified. For example, bacterial biofilms are essential to induce periodontitis, but their mere presence is not sufficient to initiate disease. It is also now recognized that the host response to these biofilms causes most of the destruction of the periodontal tissues. Codeterminants that influence the clinical severity of the disease process include environmental, genetic, and acquired factors. In general, the prevalence of advanced periodontitis and the incidence of disease progression are lower than previously believed. However, periodontitis remains the most common chronic illness. In addition, the finding that acquired systemic diseases may predispose individuals to periodontitis, and conversely that periodontitis may be a risk factor for certain systemic diseases, has expanded the scope of periodontics. These changed paradigms and their consequences with regard to selecting therapies are discussed in this review article.     

Periodontitis and diabetes interrelationships: role of inflammation

Diabetes mellitus is a systemic disease with several major complications affecting both the quality and length of life. One of these complications is periodontal disease (periodontitis). Periodontitis is much more than a localized oral infection. Recent data indicate that periodontitis may cause changes in systemic physiology. The interrelationships between periodontitis and diabetes provide an example of systemic disease predisposing to oral infection, and once that infection is established, the oral infection exacerbates systemic disease. In this case, it may also be possible for the oral infection to predispose to systemic disease. In order to understand the cellular/molecular mechanisms responsible for such a cyclical association, one must identify common physiological changes associated with diabetes and periodontitis that produce a synergy when the conditions coexist. A potential mechanistic link involves the broad axis of inflammation, specifically immune cell phenotype, serum lipid levels, and tissue homeostasis. Diabetes-induced changes in immune cell function produce an inflammatory immune cell phenotype (upregulation of proinflammatory cytokines from monocytes/polymorphonuclear leukocytes and downregulation of growth factors from macrophages). This predisposes to chronic inflammation, progressive tissue breakdown, and diminished tissue repair capacity. Periodontal tissues frequently manifest these changes because they are constantly wounded by substances emanating from bacterial biofilms. Diabetic patients are prone to elevated low density lipoprotein cholesterol and triglycerides (LDL/TRG) even when blood glucose levels are well controlled. This is significant, as recent studies demonstrate that hyperlipidemia may be one of the factors associated with diabetes-induced immune cell alterations. Recent human studies have established a relationship between high serum lipid levels and periodontitis. Some evidence now suggests that periodontitis itself may lead to elevated LDL/TRG. Periodontitis-induced bacteremia/endotoxemia has been shown to cause elevations of serum proinflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), which have been demonstrated to produce alterations in lipid metabolism leading to hyperlipidemia. Within this context, periodontitis may contribute to elevated proinflammatory cytokines/serum lipids and potentially to systemic disease arising from chronic hyperlipidemia and/or increased inflammatory mediators. These cytokines can produce an insulin resistance syndrome similar to that observed in diabetes and initiate destruction of pancreatic beta cells leading to development of diabetes. Thus, there is potential for periodontitis to exacerbate diabetes-induced hyperlipidemia, immune cell alterations, and diminished tissue repair capacity. It may also be possible for chronic periodontitis to induce diabetes.     

微小RNA介导的牙周炎与动脉粥样硬化相关机制的研究进展

牙周炎是一种主要由菌斑生物膜所引起的牙周支持组织慢性炎症破坏性疾病,与宿主的免疫反应相关。牙周致病菌可通过一过性菌血症进入血液循环系统,引发血管炎症反应,增加心血管疾病患病风险。微小RNA(microRNA)作为近年来小分子RNA的研究热点,可在表观遗传学水平调控基因表达,参与炎症调节。本文综述了牙周致病菌通过microRNA调控免疫炎症反应的机制,从而介导动脉粥样硬化的发生、发展,为牙周炎与动脉粥样硬化疾病关联的分子机制研究提供新的思路。此外,通过探索动脉粥样硬化与牙周炎相关特异性microRNA的表达模式,可为未来诊断或治疗心血管疾病提供新的参考。     

Personal risk factors for generalized periodontitis

Abstract Periodontitis is generally considered to be a consequence of an unfavourable host-parasite interaction in which bacteria are the determinants of disease. An intense search continues for the bacteria, specific or non-specfic, that are responsible for periodontitis and various forms of the periodontal diseases have been associated with, and are widely believed to be caused by, specific bacterial groups. However, the distribution of periodontopathic bacteria is far wider than the distribution of periodontitis, indicating that the association between bacteria and periodontitis is weak. This paper proposes a paradigm for the etiology of generalized periodontitis in which ‘host’ factors are not only those triggered by bacteria (the agent) but are also those personal factors that influence the outcome of the host/parasite relationship. The personal factors that diminish the efficiency of host defence may include psycho-social stress from the social environment, factors from the lifestyle such as diet, smoking and alcoholism and systemic factors such as intercurrent disease or deficiencies within the immune inflammatory system. A model is described in which the interaction of personal factors with the social environment provides the potential for the initiation of periodontitis. Biological variation is significant and the combination of factors that cause generalized periodontitis or any other chronic disease in one individual may not result in dental or any other chronic disease in another.     

Odanacatib,A Cathepsin K‐Specific Inhibitor,Inhibits Inflammation and Bone Loss Caused by Periodontal Diseases

Background: Periodontitis is a bacteria‐induced inflammatory disease mainly affecting periodontal tissues, leading to periodontal inflammation, bone breakdown, and loss of the tooth. The main obstacle for treating periodontitis effectively is the difficulty in finding a target that can inhibit bone loss and inflammation simultaneously. Recent studies showed that cathepsin K (CTSK) might have functions in the immune system besides its role in osteoclasts. Thus, targeting CTSK would have a potential therapeutic effect in both the bone system and the immune system during the progression of periodontitis. Methods: In the current study, a small molecular inhibitor (odanacatib [ODN]) is explored to inhibit the function of CTSK in a bacteria‐induced periodontitis mouse model. Results: The application of ODN decreased the number of osteoclasts, macrophages, and T cells, as well as the expression of Toll‐like receptors (TLRs) in the periodontitis lesion area. Furthermore, lack of CTSK inhibited the expression of TLR4, TLR5, and TLR9 and their downstream cytokine signaling in the gingival epithelial cells in periodontitis lesions, demonstrating that the innate immune response was inhibited in periodontitis. Conclusion: The present results show that inhibition of CTSK can prevent bone loss and the immune response during the progression of periodontitis, indicating that CTSK is a promising target for treating inflammatory diseases such as periodontitis by affecting both osteoclasts and the immune system.     

The role of adipokines in periodontal infection and healing

Periodontitis is a chronic inflammatory disease of the periodontium, which is caused by pathogenic bacteria in combination with other risk factors. The bacteria induce an immunoinflammatory host response, which can lead to irreversible matrix degradation and bone resorption. Periodontitis can be successfully treated. To achieve regenerative periodontal healing, bioactive molecules, such as enamel matrix derivative (EMD), are applied during periodontal surgery. Recently, it has been shown that obesity is associated with periodontitis and compromised healing after periodontal therapy. The mechanisms underlying these associations are not well understood so far, but adipokines may be a pathomechanistic link. Adipokines are bioactive molecules that are secreted by the adipose tissue, and that regulate insulin sensitivity and energy expenditure, but also inflammatory and healing processes. It has also been demonstrated that visfatin and leptin increase the synthesis of proinflammatory and proteolytic molecules, whereas adiponectin downregulates the production of such mediators in periodontal cells. In addition, visfatin and leptin counteract the beneficial effects of EMD, whereas adiponectin enhances the actions of EMD on periodontal cells. Since visfatin and leptin levels are increased and adiponectin levels are reduced in obesity, these adipokines could be a pathomechanistic link whereby obesity and obesity‐related diseases enhance the risk for periodontitis and compromised periodontal healing. Recent studies have also revealed that adipokines, such as visfatin, leptin and adiponectin, are produced in periodontal cells and regulated by periodontopathogenic bacteria. Therefore, adipokines may also represent a mechanism whereby periodontal infections can impact on systemic diseases.     

Association between periodontitis and COVID-19 severity in a tertiary hospital: A retrospective cohort study

IntroductionPeriodontitis is a chronic inflammatory disease caused by biofilm accumulation resulting in loss of periodontal attachment which could be linked to systemic implications. Coronavirus disease of 2019 (COVID-19) is a disease caused by SARS-CoV-2 that triggers damage to the lungs and other organs. COVID-19 and periodontitis share similar risk factors such as smoking, obesity, old age, and diabetes mellitus. Studies noted that periodontitis along with some systemic diseases has increased mortality. Thus, this study aims to examine the association of periodontitis with COVID-19 outcomes.MethodsThis observational study included periodontitis group and non-periodontitis group for COVID-19 outcome assessment. Inclusion criteria were applied to select adults (≥18 years old) who showed at least one dental visit, and were isolated or admitted due to a COVID-19 complication (i.e. in-ward, ICU, or death). Exclusion criteria were patients with no active dental records. The periodontal status was examined from posterior bitewings and panoramic radiographs. The primary outcome assessed was COVID-19 complications versus no admission.Results and discussionThis study was the first of its kind as a retrospective cohort study to assess the association between periodontitis and COVID-19 severity in Riyadh, Saudi Arabia. Our findings revealed that periodontitis is statistically associated with COVID-19 severity. Periodontitis patients were three times more likely to have COVID-19 complications (p = 0.025). Diabetes (p = 0.004) and hypertension (p = 0.016) patients were 3.5 times more likely to have COVID-19 complications.ConclusionUnderstanding the potential association between periodontitis and COVID-19 through systemic inflammation might be a pathway to achieve high quality medical care.     

白细胞介素17与牙周炎相关性的研究进展

牙周炎是由牙周致病菌所致的牙周组织慢性炎症性,破坏性疾病。IL-17是一种主要由T细胞产生的促炎因子,参与牙周炎的发生、发展,并可能与牙周炎严重性相关。本文就IL-17参与牙周炎症免疫应答反应及牙槽骨吸收的机制做一综述,旨在阐明IL-17参与牙周疾病的研究现状。     

牙周基础治疗调节2型糖尿病患者代谢的研究进展

牙周炎与糖尿病密切相关,糖尿病是牙周炎的全身促进因素之一,牙周炎会加重糖尿病的病情和代谢紊乱程度。牙周基础治疗在这个双向关系中意义重大,能显著改善牙周支持组织状态、降低血清和龈沟液中炎症因子的表达,研究发现这与牙龈卟啉单胞菌fimA II型减少和内皮祖细胞免疫炎症基因等体内相关炎症基因表达降低有关。一些研究还表明牙周基础治疗能减少胰岛素拮抗脂肪因子释放、增加胰岛素敏感脂肪因子生成,缓解胰岛素抵抗;或因加强脂肪组织代谢相关基因和炎症标志物基因的表达,而对患者的糖脂代谢有益。因此,明确牙周基础治疗对2型糖尿病伴牙周炎患者的影响及相关机制,可为防治2型糖尿病及其并发症提供新的理论依据。