Periodontal-systemic health interactions: challenging the boundaries of dental medicine

The modern dentist fulfils both the surgeon and the physician (dental medicine) roles, and the latter is becoming increasingly important as the boundaries between oral health and general or systemic health become blurred. The impacts of systemic health and lifestyle behaviours on oral health are now well accepted, not only in dentistry but also in allied health fields.1 More than ever, all members of the oral health team are recognizing that advice and treatment given for an oral condition can impact on other aspects of the patient's health.

In the past decade, there has been an explosion of research regarding potential interactions between a patient's general health and their periodontal status. The topics of diabetes mellitus, cardiovascular disease, and premature birth/low birth weight have been the focus of much of this research, which has been steadily moving from epidemiological studies of statistical associations between factors, through to animal model studies, and more recently into intervention studies where the effects of dental treatment on systemic parameters can be measured directly. Statistical association can occur because of common risk factors, such as genetic and lifestyle factors. It is more intriguing to consider that there may be cause-and-effect interactions which are bi-directional, and much contemporary research in the area is taking this wider view.

Cardiovascular disease

The concept of an interplay between periodontitis and systemic health has precedent in terms of chronic infections of various types also affecting diabetes mellitus, cardiovascular disease, pregnancy and in-utero development. An interplay between chronic infection and disease at distant sites is well documented, for chronic respiratory infections and urinary tract infections. It is now recognized that chronic oro-dental infections may make a substantial contribution to the overall burden of infection carried by the body, a point of particular importance given the lack of pain and symptoms with periodontitis. Moreover, "oral bacteria are badly behaved tourists", being frequently linked to more severe disease states when outside their normal confines of the oral cavity.

An increased severity of cardiovascular disease has been linked to chronic infections of various sorts because of the generation and release into the circulation of a number of highly potent pro-inflammatory mediators, such as Interleukin-1 (IL-1), Interleukin-6, tumor necrosis factor (TNF), and prostaglandin E2, which can themselves affect multiple normal human body functions,² and trigger the release of additional mediators such as C-reactive protein from liver cells. There is evidence that IL-1 and TNF may exert pro-coagulant effects on the blood vascular system, and may alter the behaviour of endothelial cells, thereby encouraging their accumulation of lipids.³ Thus, periodontitis induces systemic inflammation which, in turn, increases the risk for cardiovascular disease and pregnancy complications. In this regard, it is important to note that periodontal infection or inflammation increases atherosclerosis and pregnancy complications, whereas periodontal therapy reduces markers of systemic infection.

The potential health impacts for the community of preventing and treating periodontal inflammation are difficult to understate, given that, according to WHO statistics, cardiovascular disease is the principal cause of death in developed countries, accounting for some 50% of all deaths (in developing countries, it causes 16% of all deaths). Current intervention studies are examining whether periodontal therapy can reduce adverse events (acute myocardial infarction, cerebrovascular accident). Similarly, there is some early work from the University of North Carolina which suggests that periodontal therapy reduces the rate of preterm delivery.

Chronic infections such as those caused by Chlamydia pneumoniae and periodontopathic bacteria such as Porphyromonas gingivalis have been associated with atherosclerosis, and there is an emerging body of evidence which indicates that direct access of bacteria from the subgingival environment to the systemic circulation can lead to bacteria gaining entry to the endothelial cells which line blood vessels, as well as affecting these same cells through triggering the release of inflammatory mediators. It has been estimated by Stephen Offenbacher that loss of epithelial integrity within periodontal pockets can represent an ulcerated surface area of up to 50-72 square centimeters in contact with the subgingival plaque biofilm. Through this "wound" surface, bacteria can penetrate into periodontal and vascular tissues, and invade intra-cellularly. Recurrent transient bacteraemias also occur during everyday activities such as chewing foods and performing mechanical oral hygiene.

The concept that certain oral bacteria may be found intra-cellularly in cells in atherosclerotic plaques in distant blood vessels is a current "hot topic". Initial studies using antibodies probed vascular tissues for bacterial components (such as GroEL) that may cross-react with important human proteins such as heat shock protein (hHSP 60). A careful study of carotid artery atheromas conducted at the University of Queensland School of Dentistry has shown that all were positive for Porphyromonas gingivalis, while two other periodontopathic bacteria Fusobacterium nucleatum and Tannerella forsythia, were found in 84% and 48% of atheromatous plaques, respectively. These results support the concept that in some patients, cross-reactivity of the immune response to bacterial HSPs from periodontal pathogens and human proteins occurs.⁴ It is well known that inflammation is a significant component of atherosclerosis lesions, and specific immune responses are associated with atherosclerosis. Periodontal bacteria are certainly present in many of these areas; whether the bacteria initiate the inflammation is not clear; however, the most recent (August 2006) research indicates that maintenance of ongoing inflammation in atheromas seems to be enhanced by the presence of oral bacteria.⁵

Pre-term birth and low birth weight

In Australia, approximately 10% of all births are pre-term (i.e. <37 weeks gestation). Pre-term birth accounts for nearly two-thirds of all infant mortality in the Western world, and is the major cause of infant and long-term disability. Pre-term low birth weight infants have much higher mortality and morbidity rates than full-term infants. The costs of hospitalization and medical care for preterm infants are extremely high, and the quality of life of these infants is often reduced by the many growth and developmental complications which they suffer.

With regard to the effects of inflammatory mediators on pregnancy, the production of inflammatory mediators such as prostaglandin E2 can trigger uterine contraction, while IL-1 and TNF cause cessation of growth in the unborn child. Premature birth and low birth weight has been linked strongly to urinary and respiratory infections in the mother. However, these types of infections do not account for much of the unexplained risk. As a chronic infection, it is not surprising therefore, that associations between periodontitis, premature birth and low birth weight have been reported in the literature from studies in many parts of the world.⁶

A recent study of associations between maternal periodontal health and prematurity in an Australian population revealed that mothers with an unknown aetiology for premature births had significantly higher levels of calculus and deeper periodontal pockets than matched control mothers.⁷ When comparing pre-term mothers to full-term birth mothers, the pre-term mothers had significantly higher levels of calculus and plaque, and were less regular users of either dental floss or anti-bacterial mouthrinses. This study also reported that both dental and periodontal status were independently associated with premature birth, when all known risk factors were accounted for. Both maternal periodontal health and maternal oral hygiene status were strongly associated with birth prematurity. Poor maternal oral health is thought to contribute to premature birth through increased levels of endotoxins and cytokines, particularly prostaglandin E2 which triggers uterine contraction, cervical dilation and early onset of labour.

Table 1. Systemic effects of some key mediators implicated in periodontal-general health interactions.

Slide courtesy of Dr Stephen Offenbacher

Directions for the future

In light of the emerging role for oral health in a person's total health profile, the federal government introduced arrangements within Medicare for facilitating care for patients who require "medically necessary dentistry", a term which would include pregnant women and adults with advanced cardiovascular disease. Uptake of this appears to have been relatively low at this stage, however the dental profession can and should take a leading role through promoting careful periodontal assessment and regular oral hygiene care for these at-risk groups of patients.

Prevention of dental plaque-related oral diseases is more important than in the past given this wider view of linkages to health. Because gingival and periodontal inflammation can be screened for relatively easily, and are treatable, the dental component which may drive cardiovascular disease or pre-term birth is a modifiable risk factor. Thus, maintaining good oral health should receive a high priority in health planning for our patients in these groups.

About the author

Professor Laurence J. Walsh is the technology editor of Australasian Dental Practice magazine. He is also a noted commentator on and user of new technologies and is the Head of The University of Queensland School of Dentistry.

References

1. Walsh LJ. Lifestyle impacts on oral health. In: Mount GJ, Hume WR. Preservation and restoration of tooth structure, 2nd. Edition, Brisbane: Knowledge Books and Software, 2005.
2. Walsh LJ. Cytokines. In: Seymour GJ, et al. Immunology- an introduction for the health sciences. Sydney: McGraw-Hill, 1985.
3. Beck JD, Slade G, Offenbacher S. Oral disease, cardiovascular disease and systemic inflammation. Periodontol 2000. 2000; 23: 110-120.
4. Ford PJ, et al. Cross-reactivity of GroEL antibodies with human heat shock protein 60 and quantification of pathogens in atherosclerosis. Oral Microbiol Immunol. 2005 Oct;20(5):296-302.
5. Ford PJ, et al. Inflammation, heat shock proteins and periodontal pathogens in atherosclerosis: an immunohistologic study. Oral Microbiol Immunol. 2006 Aug;21(4):206-11.
6. Offenbacher S, et al. Periodontal infection as a possible risk factor for preterm low birth weight. J Periodontol. (suppl.) 1996; 67: 1103-1113.
7. Wan AKL, et al. Associations between maternal periodontal health and prematurity of newborns - a cross-sectional study of an Australian population group. Periodontol. 2002; 23: 40-49.