Periodontal disease and systemic conditions: a bidirectional relationship

For decades, physicians and dentists have paid close attention to their own respective fields, specializing in medicine pertaining to the body and the oral cavity, respectively. However, recent findings have strongly suggested that oral health may be indicative of systemic health. Currently, this gap between allopathic medicine and dental medicine is quickly closing, due to significant findings supporting the association between periodontal disease and systemic conditions such as cardiovascular disease, type 2 diabetes mellitus, adverse pregnancy outcomes, and osteoporosis. Significant effort has brought numerous advances in revealing the etiological and pathological links between this chronic inflammatory dental disease and these other conditions. Therefore, there is reason to hope that the strong evidence from these studies may guide researchers towards greatly improved treatment of periodontal infection that would also ameliorate these systemic illnesses. Hence, researchers must continue not only to uncover more information about the correlations between periodontal and systemic diseases but also to focus on positive associations that may result from treating periodontal disease as a means of ameliorating systemic diseases.     

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。     

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.     

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.     

Periodontal medicine: emerging concepts in pregnancy outcomes

The term periodontal medicine encompasses the study of the contribution of periodontal infections on several systemic conditions such as atherosclerosis, myocardial infarction, stroke, diabetes, and premature delivery. The early reports of a linkage between periodontitis and systemic conditions are gaining further support from additional epidemiological studies. The evidence continues to suggest that maternal periodontitis may bean important risk factor or risk indicator for pregnancies culminating in preterm low birth-weight deliveries. Potential mechanisms by which infectious challenge of periodontal origin and systemic inflammation may serve as a potential modifier of parturition are discussed. Furthermore, preliminary data are presented, supporting a hypothetical model in which periodontal pathogens disseminate systemically within the mother and gain access to the foetal compartment. Several aspects of this hypothetical model remain to be elucidated. Only the clarification of the mechanisms of pathogenesis of both periodontitis and premature deliveries will ultimately allow for accurate diagnoses and successful therapies. The concept of diagnosing and treating a periodontal patient to minimise the deleterious effects of this chronic infectious and inflammatory condition on systemic conditions represents both an unprecedented challenge and opportunity to our profession.     

Systemic effects of periodontitis: lessons learned from research on atherosclerotic vascular disease and adverse pregnancy outcomes

Studies conducted over the past 25 years have focussed on the role of periodontitis, an inflammatory condition of microbial aetiology that destroys the tooth‐supporting tissues, as a systemic inflammatory stressor that can act as an independent risk factor of atherosclerotic vascular disease (AVSD) and adverse pregnancy outcomes (APOs). It has been suggested that periodontitis‐associated bacteraemias and systemic dissemination of inflammatory mediators produced in the periodontal tissues may result in systemic inflammation and endothelial dysfunction, and that bacteria of oral origin may translocate into the feto‐placental unit. Epidemiological studies largely support an association between periodontitis and ASVD/APOs, independently of known confounders; indeed, periodontitis has been shown to confer statistically significantly elevated risk for clinical events associated with ASVD and APOs in multivariable adjustments. On the other hand, intervention studies demonstrate that although periodontal therapy reduces systemic inflammation and improves endothelial function, it has no positive effect on the incidence of APOs. Studies of the effects of periodontal interventions on ASVD‐related clinical events are lacking. This review summarises key findings from mechanistic, association and intervention studies and attempts to reconcile the seemingly contradictory evidence that originates from different lines of investigation.     

The “sufficient cause” model framework applied to the periodontitis-systemic diseases link

The premise for the oral-systemic diseases relationship dates to the early 20th century with the introduction of the focal infection theory that posited that oral disease affects overall health and wellbeing. While the biological plausibility for the link has been supported by experimental animal models and observational studies in humans, findings from interventional studies in which periodontal therapy failed to alleviate systemic health outcomes have often been interpreted as evidence against periodontitis contribution to the etiology of systemic health conditions. One concept of causation assumes a one-to-one correspondence between cause and effect. Nevertheless, common chronic diseases to which periodontitis is associated have multifactorial etiologies. This commentary provides an overview of Rothman's “sufficient cause” model as a framework for consideration of the oral-systemic diseases link.     

Relationship between the oral cavity and cardiovascular diseases and metabolic syndrome

The components of the human body are closely interdependent; as a result, disease conditions in some organs or components can influence the development of disease in other body locations. The effect of oral health upon health in general has been investigated for decades by many epidemiological studies. In this context, there appears to be a clear relationship between deficient oral hygiene and different systemic disorders such as cardiovascular disease and metabolic syndrome. The precise relationship between them is the subject of ongoing research, and a variety of theories have been proposed, though most of them postulate the mediation of an inflammatory response. This association between the oral cavity and disease in general requires further study, and health professionals should be made aware of the importance of adopting measures destined to promote correct oral health. The present study conducts a Medline search with the purpose of offering an update on the relationship between oral diseases and cardiovascular diseases, together with an evaluation of the bidirectional relationship between metabolic syndrome and periodontal disease. Most authors effectively describe a moderate association between the oral cavity and cardiovascular diseases, though they also report a lack of scientific evidence that oral alterations constitute an independent cause of cardiovascular diseases, or that their adequate treatment can contribute to prevent such diseases. In the case of metabolic syndrome, obesity and particularly diabetes mellitus may be associated to an increased susceptibility to periodontitis. However, it is not clear whether periodontal treatment is able to improve the systemic conditions of these patients. Key words:Cardiovascular diseases, periodontitis, metabolic syndrome, obesity, diabetes mellitus.     

The relationship between osteoporosis,osteopenia and periodontitis

A review of the literature on the reciprocal influence of osteoporosis and periodontitis. The imbalance in coupling of bone remodeling causes skeletal osteopenia and osteoporosis. Does the remodeling imbalance influence the oral bone? Both diseases are chronic, multifactorial and result at bone loss. In addition, the diseases share common risk factors such genetics, dietary, environmental and systemic factors. Different studies indicate that the skeletal bone loss in osteoporosis accelerate the decrease in bone density in oral bone. Although the differences in etiology between the two diseases some studies showed that treatment of osteoporosis improved the periodontal health. Further investigation of the mechanisms behind the relationship between osteoporosis and periodontitis may lead to common treatment strategies.     

Diagnostic & therapeutic strategies for the management of the diabetic patient

The bridge between oral and systemic health exists and becomes more concrete as data continue to emerge in support of this relationship. The medical management of diabetes is affected by the presence of chronic infections, such as periodontitis. This article reviews the pathogenesis of periodontal disease as it relates to diabetes. The author discusses patient susceptibility in terms of risk and recommends risk assessment to determine optimal treatment strategies. Patients with poorly controlled diabetes are at greater risk for developing periodontitis. The opportunity for systemic exposure to periodontal pathogens and proinflammatory mediators associated with periodontitis is discussed relative to their specific effects on patients with diabetes. The importance of good metabolic control in terms of risk for developing long-term complications of diabetes is presented and the impact of periodontitis on achieving adequate metabolic control is described. Special considerations for the management of patients with diabetes in the dental office are reviewed, including the signs and symptoms of diabetes, risk assessment for diabetes, and the challenges of "tight control" with insulin and oral agents with regards to hypoglycemia. It is recommended by the author that a thorough medical history of the patient be obtained, that the patient's medications are known, that the dentist consults with the patient's physician to assess the patient's glycemic control, and that the patient's blood glucose levels and dietary intake be monitored before treatment. Finally, the author reviews the long-term complications of diabetes, particularly the oral complications that can affect overall health. The author concludes with the belief that the treatment of periodontal diseases should not be considered optional or elective but, instead, should be a necessary and integral part of a patient's overall healthcare program.     

The periodontal infection-systemic disease link: a review of the truth or myth

Observational studies indicate periodontal infections as a risk factor for systemic conditions like cardiovascular disease and preterm low birth weight. This paper reviews and argues the biological plausibility for a periodontal infection-systemic disease link and reviews the available experimental data from animal models and human intervention trials. Five principal lines of evidence can be used to explain the biological plausibility of a link. First, infection in general has been implicated in the pathogenesis of both atherosclerosis and preterm delivery. Periodontal infection secondly causes transient and low-grade bacteraemias and endotoxaemias in patients. Thirdly, periodontal infection promotes systemic inflammatory and immune responses that may play roles in disease. Periodontal pathogens express specific virulence factors that can affect atherogenic or parturition events. Lastly, periodontal pathogens have also been isolated from non-oral tissues like atheromatous plaques. Experimental data derived from rodent and pig models indicate that infection or bacteraemias with the periodontal pathogen, Porphyromonas gingivalis, can increase atheroma size or reduce litter weights as compared to controls. While human intervention data are lacking for patients at risk for cardiovascular disease, early data indicate that periodontal therapy administered to pregnant mothers with periodontitis can reduce the incidence of preterm low birth weight deliveries. Nevertheless, more and larger intervention trials are needed before we can fully accept periodontal infection as a true risk factor in the causal pathways of cardiovascular disease and preterm low birth weight.     

Genomics of periodontal disease and tooth morbidity

In this review we critically summarize the evidence base and the progress to date regarding the genomic basis of periodontal disease and tooth morbidity (ie, dental caries and tooth loss), and discuss future applications and research directions in the context of precision oral health and care. Evidence for these oral/dental traits from genome-wide association studies first emerged less than a decade ago. Basic and translational research activities in this domain are now under way by multiple groups around the world. Key departure points in the oral health genomics discourse are: (a) some heritable variation exists for periodontal and dental diseases; (b) the environmental component (eg, social determinants of health and behavioral risk factors) has a major influence on the population distribution but probably interacts with factors of innate susceptibility at the person-level; (c) sizeable, multi-ethnic, well-characterized samples or cohorts with high-quality measures on oral health outcomes and genomics information are required to make decisive discoveries; (d) challenges remain in the measurement of oral health and disease, with current periodontitis and dental caries traits capturing only a part of the health-disease continuum, and are little or not informed by the underlying biology; (e) the substantial individual heterogeneity that exists in the clinical presentation and lifetime trajectory of oral disease can be identified and leveraged in a precision medicine framework or, if unappreciated, can hamper translational efforts. In this review we discuss how composite or biologically informed traits may offer improvements over clinically defined ones for the genomic interrogation of oral diseases. We demonstrate the utility of the results of genome-wide association studies for the development and testing of a genetic risk score for severe periodontitis. We conclude that exciting opportunities lie ahead for improvements in the oral health of individual patients and populations via advances in our understanding of the genomic basis of oral health and disease. The pace of new discoveries and their equitable translation to practice will largely depend on investments in the education and training of the oral health care workforce, basic and population research, and sustained collaborative efforts..     

The impact of ethnicity, gender, and marital status on periodontal and systemic health of older subjects in the Trials to Enhance Elders' Teeth and Oral Health (TEETH)

BACKGROUND: Few studies have examined the association between periodontitis risk, gender, and marital status in older adults. The purpose of this study was to assess if the oral health status of older subjects could be explained by differences in: 1) marital status; 2) gender; and 3) ethnicity. METHODS: Clinical and radiographic periodontal oral conditions were studied in 701 older subjects from the TEETH clinical trial. Medical conditions as well as ethnic and marital status and smoking habits were considered. RESULTS: A total of 89 married couples were identified; 40.7% of these were of European descent and 48.1% of Chinese descent. The mean age was 67.7 years (SD +/- 4.7). The men were older than the women (mean difference: 1.5 years, SD +/- 4.6, 95% confidence interval [CI]: 0.5 to 2.5, P<0.01). No significant differences in periodontal conditions were found between spouses or by marital status. Chinese descent was associated with a higher risk for periodontitis, regardless of marital status (odds ratio: 1.5, 95% CI: 1.05 to 2.04, P<0.03). CONCLUSIONS: 1) Married couples have similar social habits, similar oral health perceptions, and similar patterns of periodontal disease. 2) Dental studies including married couples do not bias data for married subjects as such. 3) Marital status has a limited impact on periodontal health but may have a greater impact on several systemic conditions, especially in widowed, divorced, or never married women. 4) Older Chinese subjects perceive themselves as being at lower risk for periodontitis but have more objective signs of periodontitis than older subjects of European descent.     

牙周炎对全身疾病和健康影响的研究进展

牙周炎是常见的慢性感染性疾病,可造成牙周支持组织破坏,是导致成年人失牙的最主要原因。此外,大量研究证明,牙周炎能通过龈下菌斑生物膜中的微生物及其产物引起全身炎症及免疫反应,可能成为一些全身疾病的危险因素。虽然牙周炎和全身疾病相互作用的具体生物学机制仍不清楚,但现有的一些研究证据确实证明了二者互相促进的关系。本文就牙周炎对全身疾病和健康的影响作简要阐述.     

Osteoporosis,jawbones and periodontal disease

The association between osteoporosis and jawbones remains an argument of debate. Both osteoporosis and periodontal diseases are bone resorptive diseases; it has been hypothesized that osteoporosis could be a risk factor for the progression of periodontal disease and vice versa. Hypothetical models linking the two conditions exist: in particular, it is supposed that the osteoporosis-related bone mass density reduction may accelerate alveolar bone resorption caused by periodontitis, resulting in a facilitated periodontal bacteria invasion. Invading bacteria, in turn, may alter the normal homeostasis of bone tissue, increasing osteoclastic activity and reducing local and systemic bone density by both direct effects (release of toxins) and/or indirect mechanisms (release of inflammatory mediators). Current evidence provides conflicting results due to potential biases related to study design, samples size and endpoints. The aim of this article is to review and summarize the published literature on the associations between osteoporosis and different oral conditions such as bone loss in the jaws, periodontal diseases, and tooth loss. Further well-controlled studies are needed to better elucidate the inter-relationship between systemic and oral bone loss and to clarify whether dentists could usefully provide early warning for osteoporosis risk. Key words:Osteoporosis, periodontitis, oral bone loss, tooth loss, edentulism, bone mineral density.     

The association between periodontal diseases and cardiovascular diseases: a state-of-the-science review

Early case-control and cross-sectional studies demonstrating associations between chronic periodontitis and cardiovascular disease (CVD) were quickly followed by secondary analyses of data available from existing longitudinal studies, which indicated that individuals with periodontitis, as determined by clinical measures, were at greater risk for CVD events. Many of these studies contained large numbers of subjects and were adjusted for traditional risk factors. Within the last 18 months, one case-control study and one longitudinal study have reported finding positive associations that were not statistically significant. The earlier studies stimulated a number of studies focused on identifying potential biological mechanisms that might underlie this association. While still early in that process, such studies have implicated a systemic role for oral microorganisms and for the quality and quantity of the host inflammatory response as key biologic processes that may underlie the association of CVD with the clinical manifestation of periodontitis. It is a positive development when changes in our knowledge regarding biologic mechanisms result in reevaluation of past studies, and this reevaluation leads to new studies that incorporate the design elements demanded by this new knowledge. In that spirit, we conclude that all longitudinal studies reported to date can be characterized as follows: none were initially designed to actually test the association of interest; almost all were restricted to clinical measures of periodontitis to index the exposure and lacked measures of infectious burden and host response; and they used a variety of cardiovascular clinical events to index the outcome and did not include subclinical measures of atherosclerosis. In addition, the longitudinal studies that failed to show a significant association between periodontitis and CVD used the least sensitive and crudest clinical measures of periodontal disease. Based upon the current state-of-the-science, all previous studies should be viewed as lacking sufficiently sensitive and comprehensive measures of periodontal disease as a systemic exposure. Since the potential health care impact of this relationship might be extensive, it is time to enter the next phase of research by conducting molecular epidemiology studies that are appropriately designed to test our current understanding of the molecular and cellular mechanisms involved.     

Infection-mediated early-onset periodontal disease in P/E-selectin-deficient mice

BACKGROUND: Retrospective and correlation studies suggest that early-onset periodontal disease may be due to a deficiency in phagocyte function, a pathogenic oral biofilm, and/or dysregulated gingival cytokine expression. Increased susceptibility to periodontal disease is therefore thought to result from multiple risk factors. METHODS: We tested this hypothesis prospectively using P/E-selectin adhesion molecule deficient mice that mimic the human syndrome leukocyte adhesion deficiency II. RESULTS: Our studies demonstrate that, in comparison to wild type animals, P/E-/- mice exhibit: spontaneous, early onset alveolar bone loss which is significant by 6 weeks of age; a 10-fold elevation in bacterial colonization of their oral cavities; and elevated gingival tissue levels of the bone resorptive cytokine IL-1alpha. Alveolar bone loss is completely prevented by prophylactic antibiotic therapy. CONCLUSIONS: These experiments provide the first prospective evidence for the multiple risk factor hypothesis of periodontal disease, and validate the first animal model for early onset periodontitis in which both the microbiota and host response can be systematically manipulated. P/E-/- animals should be useful in testing the virulence of putative periodontal pathogens, in determining the role of host resistance factors in periodontitis, in exploring the proposed relationship(s) between infection mediated alveolar bone loss and systemic health disorders, and exploring their genetic relationships.     

运用牙周特色治疗改善重度牙周炎的临床效果（附1例6年诊治随访观察报告）

牙周炎是最常见的失牙原因之一,不仅严重影响口腔健康,也是多种全身性疾病的风险因素。完善的牙周检查及系统的治疗计划是消除炎症、控制疾病进展、恢复口腔功能和美观的关键。如何尽最大可能保留存在牙周组织严重破坏的天然牙并维持其功能是口腔医生面临的挑战。文章展示了1例重度牙周炎病例的综合诊疗过程,通过完善的牙周基础治疗和恰当的手术治疗,控制了牙周炎症进展,并采用可摘局部义齿修复缺失牙,恢复口腔功能,同时定期行牙周维护治疗,随访6年,获得良好的治疗效果。基于此病例,文章探讨了重度牙周炎患牙的治疗决策,重度牙周炎诊疗中基础治疗和手术治疗的临床效果以及菌斑控制对长期维护治疗效果的作用,总结了本病例临床处理中的不足,为重度牙周炎的治疗积累了经验。     

运用牙周特色治疗改善重度牙周炎的临床效果（附1例6年诊治随访观察报告）

 牙周炎是最常见的失牙原因之一，不仅严重影响口腔健康，也是多种全身性疾病的风险因素。完善的牙周检查及系统的治疗计划是消除炎症、控制疾病进展、恢复口腔功能和美观的关键。如何尽最大可能保留存在牙周组织严重破坏的天然牙并维持其功能是口腔医生面临的挑战。文章展示了1例重度牙周炎病例的综合诊疗过程，通过完善的牙周基础治疗和恰当的手术治疗，控制了牙周炎症进展，并采用可摘局部义齿修复缺失牙，恢复口腔功能，同时定期行牙周维护治疗，随访6年，获得良好的治疗效果。基于此病例，文章探讨了重度牙周炎患牙的治疗决策，重度牙周炎诊疗中基础治疗和手术治疗的临床效果以及菌斑控制对长期维护治疗效果的作用，总结了本病例临床处理中的不足，为重度牙周炎的治疗积累了经验。     

慢性牙周炎和慢性肾病相关关系的 研究进展

慢性牙周炎不仅可以导致牙周支持组织的破坏和丧失,还与多种全身系统性疾病如高血压、糖尿病等有关.慢性肾病是一种破坏肾功能的威胁人类健康的常见的全身性疾病.近年来大量研究显示,慢性牙周炎与慢性肾病可能具有相关关系,通过治疗牙周炎有可能改善肾功能.本文就慢性牙周炎与慢性肾病相关性的流行病学调查研究、牙周治疗对慢性肾病的影响以...