Update on general health risk of periodontal disease

Objectives : To review the potential of periodontal infections to cause nonoral diseases. Therapeutic recommendations are provided to help patients and dental practitioners prevent systemic complications from periodontal infections. Findings : Systemic diseases from oral bacteria are mostly caused by transient bacteraemias, which can occur spontaneously from dental foci of infection, from mastication, brushing, flossing or other daily manipulations, or from dental treatments. Examples of systemic infections that may involve oral microorganisms include infective endocarditis, aspiration pneumonia, HIV‐related disseminated candidiasis and cancrum oris, septicaemia associated with cancer chemotherapy and radiotherapy, necrotising faciitis and various other life‐threatening infections. Inflamed gingiva constitutes a significant reservoir for herpes viruses, which have the potential to cause serious systemic diseases in immunocompromised patients. Periodontal disease may also aggravate chronic insulin insensitivity and thus interfere with glycaemic control in diabetic patients. Controversy surrounds the involvement of periodontal infections in coronary heart disease. Conclusions : Cumulative evidence suggests that periodontal disease can be an important cause of morbidity and mortality of various systemic diseases, especially in individuals exhibiting compromised host defence. Maintaining a healthy dentition and periodontium by means of daily oral hygiene practice and regular professional care is the most effective way of preventing systemic diseases from oral infections.     

Are oral and dental diseases linked to cancer?

Oral Diseases (2011) 17 , 779–784 Objective: Infection and inflammation play a role in carcinogenesis, and highly prevalent oral and dental diseases have been significantly linked to some types of cancer. This article reviews current literature in this area. Materials and Methods: Open literature review using the PubMed database and focused on publications from 2000 to 2010. Results: Numerous potential mechanisms are implicated in the oral disease/carcinogenesis paradigm, including infection‐ and inflammation‐associated cell pathology and microbial carcinogen metabolism. Poor oral hygiene is associated with oral cancer, but there is also evidence of a possible link between oral or dental infections and malignancies in general. Conclusion: Oral infections may trigger malignant transformation in tissues of the mouth and other organs. However, scientific evidence to date remains weak and further well‐conducted studies are warranted before cancer can be properly added to the list of oral infection‐related systemic diseases.     

Periodontal disease: link to cardiovascular disease

Poor oral hygiene that leads to dental infections could contribute to adverse medical outcomes such as cardiovascular disease. Twelve studies of varying degrees of design rigor have associated dental conditions, such as periodontal disease, missing teeth, and edentulousness, with either coronary heart disease or a cerebral vascular accident. Six of the studies were longitudinal so that the demonstration of the oral health parameters as significant predictors of the cardiovascular event would elevate the dental parameter to the status of a risk factor. Because dental diseases (especially periodontal disease) are treatable, the dental component is a modifiable risk factor; therefore, maintaining good oral health should receive the highest priority for a healthy life.     

Periodontal manifestations of systemic disease

Periodontitis is a chronic bacterial infection of the supporting structures of the teeth. The host response to infection is an important factor in determining the extent and severity of periodontal disease. Systemic factors modify periodontitis principally through their effects on the normal immune and inflammatory mechanisms. Several conditions may give rise to an increased prevalence, incidence or severity of gingivitis and periodontitis. The effects of a significant number of systemic diseases upon periodontitis are unclear and often it is difficult to causally link such diseases to periodontitis. In many cases the literature is insufficient to make definite statements on links between certain systemic factors and periodontitis and for several conditions only case reports exist whereas in other areas an extensive literature is present. A reduction in number or function of polymorphonuclear leukocytes (PMNs) can result in an increased rate and severity of periodontal destruction. Medications such as phenytoin, nifedipine, and cyclosporin predispose to gingival overgrowth in response to plaque and changes in hormone levels may increase severity of plaque-induced gingival inflammation. Immuno-suppressive drug therapy and any disease resulting in suppression of the normal inflammatory and immune mechanisms (such as HIV infection) may predispose the individual to periodontal destruction. There is convincing evidence that smoking has a detrimental effect on periodontal health. The histiocytoses diseases may present as necrotizing ulcerative periodontitis and numerous genetic polymorphisms relevant to inflammatory and immune processes are being evaluated as modifying factors in periodontal disease. Periodontitis severity and prevalence are increased in diabetics and worse in poorly controlled diabetics. Periodontitis may exacerbate diabetes by decreasing glycaemic control. This indicates a degree of synergism between the two diseases. The relative risk of cardiovascular disease is doubled in subjects with periodontal disease. Periodontal and cardiovascular disease share many common risk and socio-economic factors, particularly smoking, which is a powerful risk factor for both diseases. The actual underlying aetiology of both diseases is complex as are the potential mechanisms whereby the diseases may be causally linked. It is thought that the chronic inflammatory and microbial burden in periodontal disease may predispose to cardiovascular disease in ways proposed for other infections such as with Chlamydia pneumoniae. To move from the current association status of both diseases to causality requires much additional evidence. Determining the role a systemic disease plays in the pathogenesis of periodontal disease is very difficult as several obstacles affect the design of the necessary studies. Control groups need to be carefully matched in respect of age, gender, oral hygiene and socio-economic status. Many studies, particularly before the aetiological importance of dental plaque was recognised, failed to include such controls. Longitudinal studies spanning several years are preferable in individuals both with and without systemic disease, due to the time period in which periodontitis will develop.     

Correlations between dental-oral infections and cardiovascular disease

The potential role of periodontal disease, gingivitis and other dental infections as a possible chronic source of infection and inflammation represents a continuous challenge to the host organism. The high number of oral pathogens, lipopolysaccharides and soluble mediators are related to the pathogenesis of local inflammation and the initiation of systemic inflammation process, which may impair systemic health. In the last decades, studies suggested that there could be a connection between the local oral infections and several systemic conditions such as diabetes, cardiovascular disease, low birth weight and chronic obstructive pulmonary disease. Cardiovascular disease is the number one cause of death in the last century. The primary contributing factor in the majority of cardiovascular diseases is atherosclerosis. The role of infection is believed to provide a critical inflammatory stimulus that contributes to atherogenesis. The present review is a short summary of studies of the last years about the possible pathogenic role of local oral infections as a contributing factor in the initiation and progression of cardiovascular disease.     

Review: Pathogen-induced inflammation at sites distant from oral infection: bacterial persistence and induction of cell-specific innate immune inflammatory pathways

A hallmark of infection with the gram‐negative pathogen Porphyromonas gingivalis is the induction of a chronic inflammatory response. P. gingivalis induces a local chronic inflammatory response that results in oral inflammatory bone destruction, which manifests as periodontal disease. In addition to chronic inflammation at the initial site of infection, mounting evidence has accumulated supporting a role for P. gingivalis‐mediated periodontal disease as a risk factor for several systemic diseases including, diabetes, preterm birth, stroke, and atherosclerotic cardiovascular disease. A growing number of in vitro studies have demonstrated that P. gingivalis infection stimulates cell activation commensurate with expected responses paralleling inflammatory atherosclerotic‐type responses. Furthermore, various mouse models have been used to examine the ability of P. gingivalis to stimulate chronic inflammatory plaque accumulation and recent studies have pointed to a pivotal role for innate immune signaling via the Toll‐like receptors in the chronic inflammation associated with P. gingivalis infection. In this review we discuss the pathogen and host cell specificity of these responses and discuss possible mechanisms by which this oral pathogen can induce and maintain a chronic state of inflammation at sites distant from oral infection.     

Oral health status, salivary factors and microbial analysis in patients with active gastro-oesophageal reflux disease

Aim: To present a complex oral health status including salivary factors, microbial analysis and periodontal and hygiene indices in patients with active gastro‐oesophageal reflux disease (GORD). Return of stomach contents is quite common in cases of gastro‐oesophageal reflux. Pathological acid movement from the stomach into the oesophagus and oral cavity may lead to a development of dental erosion. Long‐lasting untreated GORD may damage hard dental and periodontal tissues and alter the oral microbial environment. The quality and amount of the saliva play an important role in hard and soft oral tissues changes. Method: Fifty patients with diagnosed GORD using 24‐hour pH manometry underwent dental examination; 24 patients had active GORD and had been waiting for surgical therapy. In this patient group oral health status and salivary analysis were evaluated. Results: Indicated low salivary flow rates and buffering capacity with a low caries risk but a high risk for dental erosion progression.     

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.     

Focal infection: a new perspective on an old theory

In recent years, the controversial focal infection theory (originally presented in the early 1900s) has received a resurgence of support, as oral infections have been linked to several systemic conditions. This article reviews pertinent literature detailing both the historical basis of the focal infection theory and current viewpoints on the possible association between oral and systemic diseases. Dental professionals should be aware of the potential negative effects of oral infections on systemic health. While endodontically treated teeth have not been implicated in systemic disease, effective treatment regimens for periodontal disease may reduce the occurrence of systemic disease for certain individuals.     

Association between respiratory disease in hospitalized patients and periodontal disease: a cross-sectional study

Background: Recent research indicated that periodontal infection may worsen systemic diseases, including pulmonary disease. Respiratory infections, such as pneumonia and the exacerbation of chronic obstructive pulmonary disease, involve the aspiration of bacteria from the oropharynx into the lower respiratory tract. Methods: A group of 100 cases (hospitalized patients with respiratory disease) and a group of 100 age‐, sex‐, and race‐matched outpatient controls (systemically healthy patients from the outpatient clinic, Department of Periodontics, Government Dental College and Hospital, Calicut, Kerala, India) were selected for the study. Standardized measures of oral health that were performed and compared included the gingival index (GI), plaque index (PI), and simplified oral hygiene index (OHI). Data regarding probing depths and clinical attachment levels (CALs) were recorded at four sites per tooth and compared statistically. The χ² and Student t tests were used for statistical analyses. Results: The comparison of study‐population demographics on the basis of age, sex, education, and income showed no significant differences between groups. Patients with respiratory disease had significantly greater poor periodontal health (OHI and PI), gingival inflammation (GI), deeper pockets, and CALs compared to controls. In the case group, patients with a low income were 4.4 times more prone to periodontal disease compared to high‐income patients. Smokers had significantly higher CALs compared to non‐smokers in the control group. Conclusion: The findings of the present analysis support an association between respiratory and periodontal disease.     

Periodontal innate immune mechanisms relevant to atherosclerosis

Atherosclerosis is a common cardiovascular disease in the USA where it is a leading cause of illness and death. Atherosclerosis is the most common cause for heart attack and stroke. Most commonly, people develop atherosclerosis as a result of diabetes, genetic risk factors, high blood pressure, a high‐fat diet, obesity, high blood cholesterol levels, and smoking. However, a sizable number of patients suffering from atherosclerosis do not harbor the classical risk factors. Ongoing infections have been suggested to play a role in this process. Periodontal disease is perhaps the most common chronic infection in adults with a wide range of clinical variability and severity. Research in the past decade has shed substantial light on both the initiating infectious agents and host immunological responses in periodontal disease. Up to 46% of the general population harbors the microorganism(s) associated with periodontal disease, although many are able to limit the progression of periodontal disease or even clear the organism(s) if infected. In the last decade, several epidemiological studies have found an association between periodontal infection and atherosclerosis. This review focuses on exploring the molecular consequences of infection by pathogens that exacerbate atherosclerosis, with the focus on infections by the periodontal bacterium Porphyromonas gingivalis as a running example.     

Periodontal disease epidemiology – learned and unlearned?

The notion of periodontal disease being the major cause of tooth loss among adults was rooted in the focal infection paradigm that dominated the first half of the 20th century. This paradigm was established largely by personal opinions, and it was not until the development of periodontal indices in the mid‐1950s that periodontal epidemiology gained momentum. Unfortunately, the indices used suffered from a number of flaws, whereby the interpretation of the research results took the form of circular reasoning. It was under this paradigm that therapeutic and preventive intervention for periodontal diseases became entirely devoted to oral hygiene, as poor oral hygiene and older age were understood to explain nearly all the variation in disease occurrence. In the early 1980s, studies appeared that contradicted the concepts of poor oral hygiene as the inevitable trigger of periodontitis and of linear and ubiquitous periodontitis progression, whereby periodontal epidemiology was led into a relatively short‐lived high‐risk era. At this time, it became evident that old scourges continue to haunt periodontology: the inability to agree in operational clinical criteria for a periodontitis diagnosis and the inability to devise both a meaningful and a useful classification of periodontal diseases based on nominalist principles. The meager outcome of the high‐risk era led researchers to resurrect the focal infection paradigm, which is now dressed up as periodontal medicine. Unfortunately, these developments have left the core of periodontology somewhat disheveled and deserted.     

牙周病患者种植治疗的相关风险因素

牙周病是导致牙齿缺失的主要疾病之一。随着口腔种植技术的发展,越来越多的牙周病患者选择种植治疗修复缺失牙。牙周病与种植牙在诸多方面存在关联,且牙周病患者发生种植牙失败的风险较高,在对牙周病患者进行种植治疗之前,应对口腔局部条件、全身状况、生活习惯等进行评估,以利于种植方案的选择和风险规避。本文就牙周病患者种植治疗相关风险因素的研究进展作一综述。     

Oral Health and Mortality in Patients With Chronic Kidney Disease

Background: Factors related to mortality of patients with chronic kidney disease (CKD) were investigated to find out whether oral disease inflammatory burden or different etiology (diabetes nephropathy vs. other etiologies) of CKD could be associated with mortality. Methods: This prospective cohort study comprised 144 adults at the predialysis stage. Clinical oral and radiologic examination was made from 2000 to 2005. Patients were followed up until August 2015 (complete follow‐up time: 157 months). Cause of death could be verified from 62 of 65 patients. Clinical health data were combined with mortality records obtained from the Finland national statistics database. Number of teeth, total dental index (TDI), and periodontal inflammatory burden index were calculated to describe degree of oral inflammation. Results: Primary causes of death were cardiovascular diseases, infection, and cancer. There was a statistically significant difference in survival between diabetic nephropathy (23.8%) and other patients with CKD (59.9%; log‐rank test P <0.001). A Cox regression model showed fewer teeth, higher age, and diabetes mellitus were statistically significant independent risk factors for death. Deceased patients had fewer teeth (P <0.001) and higher TDI (P <0.05). Conclusions: Risk of death was higher among patients with diabetic nephropathy. The deceased had fewer teeth and more oral infections. However, indices used failed to show independent association with survival.     

Interleukin-6 in oral diseases: a review

Oral Diseases (2012) 18 , 236–243 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 Sjögren’s 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.     

Periodontitis as a component of hyperinflammation: treating periodontitis in obese diabetic patients

Increasing evidence points to periodontal disease as a significant risk factor in the etiology of other diseases with inflammatory components, such as cardiovascular disease and type 2 diabetes mellitus. Thus, it may be possible to reduce the risk for other diseases with an inflammatory component by maintaining a healthy periodontium. In addition to plaque and calculus, other factors such as diet, body weight, lifestyle, and environmental stress complicate the maintenance of a healthy periodontium. It is becoming more important for the general dentist to address these additional risk factors in addition to providing conventional treatment for periodontal disease. This review addresses a multifactorial approach to the treatment of periodontal disease and suggests that the "focal theory" of infection may still be relevant for oral inflammation.     

Aggressive and acute periodontal diseases

Inflammatory periodontal diseases are highly prevalent, although most of these diseases develop and progress slowly, often unnoticed by the affected individual. However, a subgroup of these diseases include aggressive and acute forms that have a relatively low prevalence but show a rapid‐course, high rate of progression leading to severe destruction of the periodontal tissues, or cause systemic symptoms that often require urgent attention from healthcare providers. Aggressive periodontitis is an early‐onset, destructive disease that shows a high rate of periodontal progression and distinctive clinical features. A contemporary case definition of this disease is presented. Population studies show that the disease is more prevalent in certain geographic regions and ethnic groups. Aggressive periodontitis is an infectious disease, and recent data show that in affected subjects the subgingival microbiota is composed of a mixed microbial infection, with a wide heterogeneity in the types and proportions of microorganisms recovered. Furthermore, there are significant differences in the microbiota of the disease among different geographic regions and ethnicities. There is also evidence that the Aggregatibacter actinomycetemycomitans‐JP2 clone may play an important role in the development of the disease in certain populations. The host response plays an important role in the susceptibility to aggressive periodontitis, where the immune response may be complex and involve multiple mechanisms. Also, genetic factors seem to play an important role in the pathogenesis of this disease, but the mechanisms of increased susceptibility are complex and not yet fully understood. The available data suggest that aggressive periodontitis is caused by mutations either in a few major genes or in multiple small‐effect genes, and there is also evidence of gene–gene and gene–environment interaction effects. Diagnostic methods for this disease, based on a specific microbiologic, immunologic or genetic profile, currently do not exist. Genetic markers have the potential to be implemented as screening tools to identify subjects at risk. This approach may significantly enhance treatment outcome through the early detection and treatment of affected subjects, as well as using future approaches based on gene therapy. At present, the treatment of this disease is directed toward elimination of the subgingival bacterial load and other local risk factors. Adjunctive use of appropriate systemic antibiotics is recommended and may contribute to a longer suppression of the microbial infection. Other aggressive forms of periodontal diseases occur in patients who are affected with certain systemic diseases, including the leukocyte adhesion deficiency syndrome, Papillon–Lefèvre syndrome, Chediak–Higashi syndrome and Down syndrome. Management of the periodontal component of these diseases is very challenging. Acute gingival and periodontal lesions include a group of disorders that range from nondestructive to destructive forms, and these lesions are usually associated with pain and are a common reason for emergency dental consultations. Some of these lesions may cause a rapid and severe destruction of the periodontal tissues and loss of teeth. Oral infections, particularly acute infections, can spread to extra‐oral sites and cause serious medical complications, and even death. Hence, prompt diagnosis and treatment are paramount.     

Increasing popularity of waterpipe tobacco smoking and electronic cigarette use: Implications for oral healthcare

Cigarette smoking increases the risk of developing several systemic conditions including cancer, cardiovascular and pulmonary diseases. Cigarette smoking is also detrimental to oral health as it increases the incidence and severity of oral cancer, periodontal diseases and peri‐implantitis, as well as impacting negatively on the dental patients' response to therapy. Therefore, consideration of smoking behavior and recommendation of smoking cessation are important parts of dental treatment planning. However, cigarettes are no longer the most popular form of tobacco use among adolescents in the United States and globally. In recent years, tobacco smoking using a waterpipe (“hookah,” “shisha”) and use of electronic cigarettes (ECIGs) has increased significantly. Thus, dental clinicians likely will treat more patients who are waterpipe and/or ECIG users. Yet, the literature on the health effects of waterpipe and ECIGs use is sparse. Both waterpipe and ECIGs deliver the dependence‐producing drug nicotine. Waterpipe tobacco smoking has been associated with periodontitis, dry socket, premalignant lesions, and oral and esophageal cancer. The health effects of long‐term ECIG use are unknown. The purpose of this review is to inform healthcare professionals about waterpipes and ECIGs, highlight emerging evidence on the biological effects of these increasingly popular tobacco products, and introduce perspectives for dental patient management and future research.     

Periodontal Disease and Incident Lung Cancer Risk: A Meta‐Analysis of Cohort Studies

Background: Periodontal disease is linked to a number of systemic diseases such as cardiovascular diseases and diabetes mellitus. Recent evidence has suggested periodontal disease might be associated with lung cancer. However, their precise relationship is yet to be explored. Hence, this study aims to investigate the association of periodontal disease and risk of incident lung cancer using a meta‐analytic approach. Methods: PubMed, Scopus, and ScienceDirect were searched up to June 10, 2015. Cohort and nested case‐control studies investigating risk of lung cancer in patients with periodontal disease were included. Hazard ratios (HRs) were calculated, as were their 95% confidence intervals (CIs) using a fixed‐effect inverse‐variance model. Statistical heterogeneity was explored using the Q test as well as the I² statistic. Publication bias was assessed by visual inspection of funnel plots symmetry and Egger’s test. Results: Five cohort studies were included, involving 321,420 participants in this meta‐analysis. Summary estimates based on adjusted data showed that periodontal disease was associated with a significant risk of lung cancer (HR = 1.24, 95% CI = 1.13 to 1.36; I² = 30%). No publication bias was detected. Subgroup analysis indicated that the association of periodontal disease and lung cancer remained significant in the female population. Conclusion: Evidence from cohort studies suggests that patients with periodontal disease are at increased risk of developing lung cancer.     

Herpesviruses: a unifying causative factor in periodontitis?

Human cytomegalovirus and Epstein‐Barr virus type 1 are discussed in this review as they relate to destructive periodontal disease in humans. Genomes of the two herpesviruses occur frequently in severe adult periodontitis, localized and generalized juvenile periodontitis, Papillon‐Lefèvre syndrome periodontitis, Down’s syndrome periodontitis, HIV‐associated periodontitis and acute necrotizing ulcerative gingivitis. Herpesvirus infections generally involve a mild or asymptomatic primary phase followed by an asymptomatic latent phase interrupted sporadically by periods of activation, where viral replication and possibly clinical disease become manifest. Herpesvirus reactivation is triggered by a number of immunosuppressing factors, some of which have also been shown to be risk indicators of periodontal disease. Available evidence argues for the involvement of active cytomegalovirus infection in the initiation and progression of localized juvenile periodontitis and possibly other types of periodontal disease. In periodontal disease, herpesviruses may cause release of tissue‐destructive cytokines, overgrowth of pathogenic periodontal bacteria, and initiation of cytotoxic or immunopathogenic events. Understanding the significance of herpesviruses in the causation and pathogenesis of destructive periodontal diseases may have important implications in future prevention and treatment of the diseases.