INTRODUCTION

Recent studies suggest that there is a possible relationship between oral infection and systemic disease. Emerging evidence is amplifying the thought that oral infection affects not only local tissues, but predisposes the body to disease distant from the oral cavity. Several inter-relationships under investigation are periodontal disease and coronary artery disease, cerebral stroke, Diabetes Mellitus, preterm low birth weight, and osteoporosis. This paper provides an overview of the current understanding of these associations and the impact research will have on the early diagnosis and treatment of peri- odontal diseases.

Recent evidence has demonstrated the relationship between periodontal disease and systemic illnesses. Oral infec- tion has been implicated as a risk factor in coronary artery disease and cerebral stroke1. One thesis relates transient bacteremia to vascular lining alteration and the formation of athromata. A sec- ond hypothesis associates transient bacteremia and rheology, the transport viscosity that affects blood flow and thromboembolic episodes. A third ele- ment is the vascular effects of local infection, demonstrating the relationship between periodontal infection and Diabetes Mellitus, whereby increased chronic levels of glycosylating hemoglobin result in the formation of receptors for aggregating glycation end products (RAGE). Chronic RAGE results in vascular damage, atheroma formation and thromboembolic incidents2.

Aggressive and chronic forms of periodontitis are bacterial infections with specific bacteria rather than host inter- actions. Generalized periodontal infections involving multiple teeth provide large surface areas from which the significant spewing of microorganisms into the blood stream can occur. Chronic bacterial interactions between blood platelets, blood vessel surfaces, and existing fatty streaks reduce blood flow, enlarge existing vascular plaques and alter the intimal lining of medium and large blood vessels at weakened sites.

Fig.1: Atherosclerotic plaque rupture (Courtesy of Dr. Eric Li and Dr. Barry Stokes, Department of Pathology, NYU Medical Center at Tisch Hospital)

Mark Herzberg, of the University of Minnesota, suggests a mechanism whereby certain bacteria induce platelets to aggregate by elaborating a protein called platelet aggregating protein (PAAP). An in vitro model shows the ability of specific microorganisms to cause platelet clumping in a model system mimicking myocardial infarctions. ECG abnormalities develop after blood infusions with S. sanguis, which are followed by increased heart rate and reduced cardiac contractibility3.

Infections are thought to be a risk factor for heart disease and stroke, and peri- odontal infection is a common, persis- tent source of chronic infection4. Multi- center interventional trials are currently underway at the Universities of Buffalo, North Carolina, and Texas at San Antonio, to test if instituting treatment of periodontal disease reduces the inci- dence of vascular disease.

Diabetes Mellitus

There is extensive literature associating Diabetes Mellitus with changes to the periodontium. Acute periodontal abscess, loss of alveolar supporting bone, premature tooth loss and poor wound healing, are complications of uncontrolled or poorly controlled Diabetes Mellitus. Diabetes is shown to aggravate an already existing periodon- titis, and uncontrolled diabetes is a risk factor to successful implant dentistry. Far less evidence exists to implicate periodontal disease as a risk factor in destabilizing controlled Diabetes Mellitus. However, exciting new evi- dence has shown that local periodontal intervention, reduces systemic glycosy- lating hemoglobin. Treatment of peri- odontal diseases resulted in a more sta- ble Diabetes Mellitus. Thus, the relation- ship between local oral infection and systemic disease was further explored and supported. Again, the interventional research noted above will continue to test the hypothesis that periodontal infection impacts systemic disease.

Preterm Low Birth Weight

Preterm low birth weight is a significant health problem with physical, emotional, and financial implications. It has been estimated that 25% of preterm low birth weight babies present with unknown eti- ologies. Early findings by Beck and Offenbacher1, at the University of North Carolina, implicate periodontal disease as a contributing factor in preterm low birth weight where other etiologies are unknown. Infections of the birth canal have been investigated by Offenbacher and co-workers5 with evidence that sug- gests an oral source of pathogenic microorganisms. This group of researchers, culturing amniotic fluids of

pregnant women with periodontal disease, demonstrated the presence of putative oral bacterial flora in the fluid. An increase of prostoglandin mediated through such infection has the potential to increase contractions, pain and pre- mature delivery, resulting in a preterm, low birth weight infant.

Fig.2: Nephrosclerosis in a patient with long-standing diabetes (Courtesy of Dr. Eric Li and Dr. Barry Stokes, Department of Pathology, NYU Medical Center at Tisch Hospital)

Osteoporosis

M. K. Jeffcoat and M. S. Reddy are inves- tigating the potential of diagnosing sys- temic osteoporosis by dental x-ray diag- nosis6. Evidence suggests that women who have been diagnosed with osteo- porosis and use tobacco suffer early tooth loss, more edentulous jaw resorp- tion and more difficulty in functioning with full dentures. Through the use of subtraction radiography, Jeffcoat and co-workers are comparing maxillary and mandibular mineralization with skeletal mineralization.

It is apparent that one cannot separate the oral environment from the rest of the body. The oral cavity can be a con- tributing factor in systemic disease, and it is itself affected by systemic disease. In April 2001, the American Academy of Periodontology collaborated with the National Institute for Cranio-facial Research in an AAP-NIDCR symposium. The symposium and partnership reviewed the evidence linking periodon- tal disease and systemic disease, and sought to establish sources of funding for future research.

Figure 3: Osteoporosis (Courtesy of Dr. Eric Li and Dr. Barry Stokes, Department of Pathology, NYU Medical Center at Tisch Hospital)

Conclusion

The evidence that periodontal disease impacts systemic illness is continually emerging and provides compelling sup- port. Current and future research will focus on tracing oral infection to areas outside the oral cavity through biotyping and through interventional therapy, as ways to test the thesis that eliminating local oral disease improves systemic disease outcomes. More interventional evidence, such as that found in the link between periodontitis resolution and a reduction of glycosylating hemoglobin, is needed to confirm its link with other systemic disease.

References

1. JD. Beck, S. Offenbacher, R. Williams, P Gibbs and R. Garcia. Periodontitis: A risk factor for coro- nary heart disease? Periodontal Disease and Human Health. New Directions in Periodontal Medicine. Sunstar-Chapel Hill Symposium 97.
2. E. Lalla, E. Weidman, I. B. Lamster and A. M. Schmidt. Advanced glycation endproducts in dia- betic periodontal disease. Periodontal Disease and Human Health. New Directions in Periodontal Medicine. Sunstar-Chapel Hill Symposium 97.
3. M. C. Herzberg and M.W. Meyer. Dental plaque, platelets and cardiovascular disease. Periodontal Disease and Human Health. New Directions in Periodontal Medicine. Sunstar-Chapel Hill Symposium 97.
4. WJ. Loesche, BL. Dominguez, M. Terpenning, C. Kerr and T. Schork. Relationship between dental disease and cerebral vascular accidents in elder- ly veterans. Periodontal Disease and Human Health. New Directions in Periodontal Medicine. Sunstar-Chapel Hill Symposium 97.

5. S. Offenbacher, PG. O’Reilly, H. Jared, SS. Socransky and JD. Beck. Pathogenic mecha- nisms of periodontitis-associated pregnancy complications. Periodontal Disease and Human Health. New Directions in Periodontal Medicine. Sunstar-Chapel Hill Symposium 97.

   6.  M. K. Jeffcoat and M. S. Reddy. Sysytemic osteo- porosis and oral bone loss. Periodontal Disease and Human Health. New Directions in Periodontal Medicine. Sunstar-Chapel Hill Symposium 97.