From focal infections to periodontal medicine

 

Christos D.R. Kalpidis

Lecturer, Department of Periodontology and Implant Biology, School of Dentistry, Aristotle University, Thessaloniki, Greece

 

Panos N. Papapanou

Professor and Chair, Division of Periodontics, College of Dental Medicine, Columbia University, New York, NY, USA

 

Abstract

Periodontal diseases were considered in the past as simple microbial infections of the periodontium, but nowadays they are conceived as local pathological conditions with a potential to affect remote sites of the body. Periodontal medicine is an emerging scientific field aiming to explore the apparent impact of periodontal disease on systemic health. Epidemiological evidence has associated periodontitis with a growing list of systemic conditions, including cardiovascular diseases, diabetes mellitus, adverse pregnancy outcomes, osteoporosis, rheumatoid arthritis, chronic respiratory conditions, and chronic kidney disease. The observed associations are thought to be the result of either a direct periopathogenic infectious insult or a low-grade systemic inflammatory response induced by periodontitis.

Several intervention studies also reveal a positive effect of periodontal treatment on related systemic diseases and adverse outcomes. Other intervention trials failed to demonstrate a protective effect, and still, others demonstrated a significant impact on several surrogate disease markers. Epidemiological and intervention studies so far demonstrate correlations of varying strengths between periodontal and systemic diseases but not a strict causal association. Clinicians should inform patients about the potential systemic health risks of periodontal disease in the context of the currently available evidence. Undoubtedly, substantial additional research is required to establish definitive conclusions on the nature of the relationship between periodontitis and systemic diseases.

Analecta Periodontologica 2009; 20:11-17

A plethora of documents from antiquity to modern times have reported an apparent association between oral infections and extra-oral pathological conditions, including arthritis, epilepsy, gastritis, pneumonia, septicemia, and cardiac episodes (O’Reilly and Claffey 2000). The concepts of “oral sepsis” (Hunter 1900) and “focal infection” (Billings 1912) were formally introduced to the medical literature at the beginning of the 20th century. According to these theories, pathogenic bacteria or microbial waste products from the first “focus,” usually the mouth, spread through the blood supply to induce infections at distant regions of the body (Billings 1912). Dentistry was incriminated of placing septic prosthetic constructions in the oral environment, and proponents of the focal infection theory advocated multiple extractions of teeth and removal of tonsils to improve systemic health (Hunter 1900, 1910). However, the long-lasting practice of indiscriminate extraction of all periodontally or endodontically involved teeth failed to result in relief of symptoms or to reduce the incidence of the allegedly related systemic diseases. During subsequent decades, lack of documentation led to the rejection of the focal infection hypothesis, except for cases of bacterial endocarditis in certain high-risk patient populations.

 

Cardiovascular diseases

A new era in the oral-systemic connection was introduced in the late 1980s by the emerging evidence of an association between poor dental health and acute myocardial infarction (Mattila et al. 1989). Over the following two decades, epidemiological studies confirmed an independent association between periodontal and cardiovascular diseases despite several common risk factors with probable confounding effects (Bahekar et al. 2007). Similar studies also revealed a correlation between untreated periodontitis and surrogate markers of cardiovascular conditions, including endothelial dysfunction, subclinical carotid atherosclerosis, and inflammatory biomarkers in the peripheral blood. The detection of periopathogenic bacteria in atheromatic lesions and pertinent in vivo animal experimentation further supported the role of infection in atherogenesis. Moreover, the chronic low-grade systemic inflammatory burden sustained by periodontal infection was proposed as an additional pathogenetic mechanism (Kebschull et al. 2010).

Despite the observed epidemiological associations and the apparent biologically plausible link, the Periodontitis and Vascular Events (PAVE) pilot randomized clinical trial failed to demonstrate a protective effect of nonsurgical periodontal treatment in reducing the risk of a second myocardial infarction in individuals with a history of cardiovascular disease (Beck et al. 2008). Nevertheless, several intervention studies indicate that periodontal treatment may improve several surrogate markers for cardiovascular diseases including endothelial dysfunction, levels of systemic inflammatory mediators such as C-reactive protein and interleukin-1, and serum lipid profiles (Kebschull et al. 2010). The logistics of randomized controlled intervention trials that evaluate the ability of periodontal treatment to reduce the incidence of cardiovascular diseases are challenging because of the several decades long development of clinically significant atherosclerosis, the required recruitment of large population samples, and the ethical issues related to monitoring of untreated periodontitis.

 

Diabetes mellitus

Accumulated data have also established that diabetic patients suffer from more severe, extensive, and progressive periodontal disease compared with nondiabetic individuals (Taylor and Borgnakke 2008, Chávarry et al. 2009). The molecular and cellular mechanisms that lead to extensive diabetic vascular complications throughout the body are also responsible for the detrimental effects of diabetes on periodontal tissues: reduced neutrophil and increased macrophage function, overproduction of inflammatory mediators, accumulation of advanced glycosylation end products, and impaired wound-healing potential (Mealey and Oates 2006). The exaggerated inflammatory response to periopathogenic bacteria accounts for the more severe periodontal destruction observed in diabetic patients.

On the other hand, diabetic patients with advanced periodontal disease seem to experience poorer glycemic control and present with a greater risk for serious life-threatening cardiovascular and kidney complications (Mealey and Oates 2006). Recent meta-analyses demonstrate that nonsurgical periodontal therapy with or without the use of systemic or local antibiotics improves glycemic control, as expressed by the levels of glycosylated hemoglobin (HbA1c) (Simpson et al. 2010, Teeuw et al. 2010). Thus, experimental, epidemiological, and clinical data have established over the years the concept of a “bidirectional relationship” between diabetes mellitus and periodontal disease (Lalla et al. 2010).

 

Pregnancy complications

Infections and inflammatory processes are established risk factors for adverse pregnancy outcomes. Even though a large body of evidence demonstrates a positive association between periodontitis and preterm birth or low birth weight, several negative epidemiological studies have been published as well (Bobetsis et al. 2006). Heterogeneity among studies with respect to population race/ethnicity, sample size, periodontal disease definitions, and additional methodological issues related to study design seems to account for the observed variability. Recent large multicenter trials reported that scaling and root planing provided during the second trimester did not result in a reduction of adverse negative obstetrical outcomes (Michalowicz et al. 2006, Offenbacher et al. 2009, Macones et al. 2010). However, the intervention studies demonstrated the safety of treating periodontal disease in the second or third trimester of pregnancy.

 

Osteoporosis

Epidemiological studies have documented a significant association between osteoporosis and periodontal disease. Clinical trials have demonstrated the relationship between osteoporosis, tooth loss, and alveolar bone loss, but conflicting data have also been reported in the literature (Geurs 2007). Part of the periodontal destruction may be attributed to systemic bone loss. Several underlying linking mechanisms have been proposed, including increased susceptibility of the jaw bone with low bone density, systemic factors of bone remodeling that modify the local periodontal tissue response, and the apparent involvement of estrogen deficiency in the release of bone-resorbing cytokines (Wactawski-Wende 2001). Although low systemic bone mass probably affects alveolar bone density, additional studies are required to determine the role of osteopenia and osteoporosis in the prevalence, severity, and progression of periodontal disease.

 

Rheumatoid arthritis

Rheumatoid arthritis, an immune-mediated inflammatory disease with a distinct environmental and genetic background, also appears to be interrelated with advanced periodontitis (Bartold et al. 2005). Even though most epidemiological studies indicate a positive association, the strength of this association is uncertain because of inherent methodological inadequacies (de Pablo et al. 2009). Common inflammatory tissue and bone destruction pathways seem to be the underlying biological mechanisms connecting these two chronic diseases (Bartold et al. 2005, de Pablo et al. 2009). Scaling and root planing tend to reduce rheumatic clinical signs and symptoms. On the other hand, novel anti-inflammatory therapies for the treatment of rheumatoid arthritis may also be applicable to the management of periodontal disease in the future (Bartold et al. 2005).

 

Chronic respiratory diseases

Microbiological and epidemiological studies also suggest an association between periodontitis and chronic respiratory diseases in special category populations such as institutionalized individuals, bedfast elderly people, or patients admitted to intensive care units (Scannapieco et al. 2003). Aspiration of pathogenic bacteria from the oropharynx to the lower respiratory tract may induce chronic respiratory pathological conditions, including nosocomial pneumonia and chronic obstructive pulmonary disease. Enzymes related to periodontal disease and cytokines derived from periodontal tissues may also be involved in the pathogenesis of respiratory diseases (Scannapieco 1999). Intervention trials indicate that oropharyngeal decontamination or improvement of oral hygiene by mechanical or chemical means significantly reduces the frequency of respiratory infections in high-risk groups (Scannapieco et al. 2003). However, the role of periodontitis in the occurrence of respiratory diseases is still not completely elucidated, and studies have failed to demonstrate a reduction in the incidence of chronic respiratory diseases in elderly institutionalized individuals by means of oral interventions.

 

Chronic kidney disease

Finally, a novel association was proposed fairly recently between chronic kidney disease and periodontitis. Chronic kidney disease is characterized by a state of chronic inflammation, and systemically elevated inflammatory mediators have been suggested as the underlying biological link (Craig 2008). Studies on the prevalence of periodontitis in chronic kidney disease patients and trials associating periodontal destruction and renal parameters support a relation between the two chronic diseases (Scannapieco and Panesar 2008), but the findings are not always consistent.

 

Effects of bisphosphonates

The term “periodontal medicine” was originally proposed by Offenbacher (1996) to describe the impact of oral infection on systemic health. However, periodontal medicine is, from a semiological standpoint, much broader because, apart from the investigation of the relation between periodontal disease and other pathological conditions, it also explores interrelations between periodontology and medicine. In this broader context, periodontal medicine encompasses the recently evolved implications of bisphosphonate use in dentistry (Woo et al. 2006). Bisphosphonates are powerful antiosteoclastic agents, currently widely used in the management of osteoporosis, metastatic bone cancers, and malignant hypercalcemia. Clinicians should be aware of the potential detrimental effects of bisphosphonates in patients receiving dental interventions, including orthodontic therapy, implant placement, or tooth extractions. More important, bisphosphonates have been implicated in osteonecrosis of the jaws, a serious complication characterized by exposed, necrotic, non-healing bone (Woo et al. 2006). Dental treatment of patients receiving bisphosphonates should be performed under specific guidelines provided by related scientific associations.

 

Periodontal medicine

The effects of periodontal disease on other pathological conditions are thought to be the result of either a direct infectious insult or a low-grade systemic inflammatory response induced by periodontal infection. A direct effect is attained with migration of bacteria from subgingival periodontal biofilms to distant body sites through blood circulation. Transient bacteremias are monitored not only after periodontal therapeutic interventions, but also during regular periodontal probing, mastication, and even tooth brushing (Crasta et al. 2009).

Epidemiological and interventional studies so far demonstrate correlations of varying strengths between periodontal and systemic diseases but not a strict causal association. How then should clinicians translate this knowledge into everyday practice? Periodontal patients with at least one known major risk factor for cardiovascular diseases, such as smoking, immediate family history, or dyslipidemia, should be advised to consider a medical evaluation. Diabetic patients should be warned about the risk of developing more extensive or severe periodontal problems, and those with moderate to advanced periodontitis should be notified about the emerging benefit of periodontal treatment for glycemic control. Pregnant women with periodontal disease should be informed that they may be at higher risk for adverse pregnancy outcomes. Similar informative discussions apply to the other systemic conditions that seem to be interconnected with periodontitis. However, on the basis of the currently available data, patients should be approached in a careful and informative way rather than in an aggressive, compulsory manner. Clinicians must impart available knowledge to patients or their relatives and discuss possible inquiries. Informing patients about the potential systemic health risks of periodontal disease is clearly different from adopting scare tactics to promote treatment acceptance and to increase the demand for dental care.

We are fortunate to be oral health care providers in the era of periodontal medicine. The scientific community has learned from the mistakes of the focal infection dogma and is now cautiously exploring this exciting and highly promising field. Certainly, substantial additional research is required to establish definitive conclusions on the nature of the association between periodontitis and systemic diseases. However, the development of periodontal medicine will undoubtedly strengthen the traditionally tight ties between dentistry and medicine.

 

Christos D.R. Kalpidis, Editor-in-Chief

Panos N. Papapanou, Associate Editor