Originally published in Dental Abstracts, Volume 66, Issue 1
Background: Periodontitis is a chronic inflammatory disease in which dysbiotic plaque biofilms cause destructive inflammatory responses, leading to destruction of the periodontal attachment and underlying bone. Mild periodontitis may affect up to half of adults and more than 60% of older adults. Eleven per cent of the world population may be affected by severe periodontitis. A growing body of evidence has linked periodontal disease to many systemic and chronic diseases, including most of the leading causes of death in the United States. Most recently, new advances have increased understanding of the etiology and pathogenesis of periodontitis, risk factors for its development, and the epidemiology and mechanisms of its associations with systemic disease. The authors present a review and update on associations of periodontal and systemic diseases.
Microbiota, inflammation, and genetics
Lack of oral hygiene leads to dysbiosis of the subgingival microbiota and thus to gingivitis. The microbiology of periodontitis is less clear, but is linked to further shifts in microbial communities and emergences of overt pathogenic organisms. This dysbiosis likely stems from dysregulation of host immune and inflammatory responses. Aberrant immune responses are related to intrinsic and extrinsic responses; genetic studies have identified at least 65 genes associated with periodontitis. These inherited risk factors may modulate the abnormal immune responses, which may also be seen in other chronic inflammatory diseases. Epigenetic modifications of DNA, which may be inherited as well as acquired, may also affect host immune function.
Diabetes and cardiovascular disease
People with diabetes are at increased risk of periodontal disease, an association which may reflect common risk factors or direct causal associations. Both human and animal studies suggest that diabetes and hyperglycemia may induce a hyperinflammatory state in infected periodontal tissues. Periodontal disease has been linked to worsening diabetic control and more-severe diabetic complications, as well as higher all cause and cardiovascular mortality. These associations occur mainly via the inflammatory response, with host-parasite interactions triggering “dumping” of host-derived mediators. Periodontal treatment leads to improved diabetic control: glycosylated hemoglobin levels may decrease by up to 1% within a few months after treatment. Epidemiologic studies show that people with periodontitis have a higher incidence of atherosclerotic disease, independent of other risk factors. Although these effects are generally modest, they increase with periodontitis severity. Microbial and inflammatory/immunologic mechanisms have been proposed by which periodontal disease may influence atheroma lesions. Randomized trials have shown that periodontal treatment can reduce serum inflammatory mediators, although there is no evidence of reduction in cardiovascular disease risk. Strong evidence suggests a synergistic effect between periodontitis and obesity, leading to metabolic dysfunction. Modest associations between periodontitis and metabolic syndrome (including obesity, dyslipidemia, hyperglycemia, and hypertension) have also been reported, based mainly on cross-sectional data.
Adverse pregnancy outcomes
Several studies have linked periodontitis to adverse outcomes of pregnancy, including low birth weight, preterm birth, and preeclampsia. However, other studies have reported conflicting findings; the discrepancy likely reflects differences in the definition and prevalence of periodontitis. There are also contradictory results on whether periodontal treatment reduces the risk of adverse pregnancy outcomes. Direct mechanisms involving local infections and indirect mechanisms involving inflammatory mediators have been proposed.
Other chronic diseases
Emerging evidence suggests an association between periodontitis and rheumatoid arthritis, largely focusing on Porphyromonas gingivalis as the source of hyper-citrullination activity. Based on a few epidemiologic studies, there are plausible mechanisms by which periodontal disease might lead to an increased risk of cancer. Evidence is strongest for associations with head and neck and esophageal cancer, less so for gastric cancer. Shared flora between the oral and pulmonary microbiomes might contribute to pulmonary disease, particularly in the presence of impaired host defense mechanisms. Possible associations with Alzheimer’s disease and other cognitive disorders have been explored. Most of these studies report positive associations, particularly with long-term exposure. Mechanisms involving both chronic neuroinflammation and pathogens crossing the blood-brain barrier have been proposed.
Discussion: Although the current findings are not always straightforward, recent reviews present evidence of associations between periodontal disease and a wide range of systemic diseases. This research knowledge has generally been slow to affect clinical practice, although a growing number of studies suggest that periodontal treatment may positively affect diabetes control and patient outcomes. The impact of periodontal disease on quality of life and other patient-based outcomes is a relatively new area of investigation.
