What the Future May Hold

The views expressed in this interview are the author’s.

Q. What was the first connection between oral and systemic health that you made as a researcher?
A. In the 1980s we hypothesized that there was some abnormality in the immune response of patients who had localized juvenile periodontitis, a condition that causes bone loss in young individuals from 10 years of age to 18 years of age and is called aggressive periodontitis. It’s a fairly rare condition affecting approximately 1% of adolescents. What we found is that the neutrophils (white blood cells) of these patients had a reduced chemotactic ability (ie, reduced ability to migrate to the site of infection).¹ This was our first finding that related a systemic condition to periodontal diseases.

The results of that study led to the investigation of other conditions where neutrophils were abnormal to determine if periodontal diseases were more severe in these patients. Diabetes was the first disease we looked at. We studied a large population of Native Americans, who have the world’s highest incidence of diabetes—about 40%.² We studied the Pima Indians who live in the Gila River Indian Community between Phoenix and Tucson in Arizona. There are about 5,000 Native Americans who live on the reservation and most of them receive their medical and dental care at one site, the Sacaton Hospital and Dental Clinic. So we set up a study there that evaluated their periodontal disease status, caries status, as well as other oral and general health conditions over a 7-year time period.³ We were able to study almost 80% of the population. We found that periodontal diseases were more severe in those who had diabetes as compared to those who didn’t have diabetes. These findings have been reproduced in other populations providing strong evidence that periodontal disease is a complication of diabetes.

Next we studied the effects of periodontal diseases on diabetes. We found that those individuals who had diabetes and also suffered from periodontal infections had worse glycemic control over time. This was quite a revelation because it clearly demonstrated the effects of periodontal diseases on systemic health. We then investigated whether the treatment of periodontitis would improve glycemic control, and in fact it did.⁴ This periodontal intervention study has been reproduced in other diabetic populations and is now being tested in large multi-center trials to determine the generalizability and extent and duration of improvement in glycemic control.

Then we addressed the complications of diabetes. We asked if a patient who has diabetes and also periodontal disease has worse complications from the diabetes. We found that those who have diabetes and periodontal diseases have a significantly greater risk of dying from heart disease and diabetic nephropophy (kidney disease) over the subsequent 12 years. Hence, not only does periodontitis make glycemic control worse but it also contributes to the worsening of the complications of diabetes. This provides great incentive to aggressively prevent and treat periodontal diseases in patients who have diabetes. We are currently studying how we can better use the dental office to assist in the management of diabetes both from the dental standpoint to minimize periodontitis, but also to minimize complications of diabetes. We feel the dental office is an important point-of-contact with the health care system and can be used in screening for undiagnosed diabetes, for those at risk for diabetes, as well as to manage periodontal disease to assist in the management of diabetes.

NEW ORAL/SYSTEMIC LINKS

Q. Many new oral/systemic links are currently being studied. Which do you think are the most compelling?
A. The link between periodontal diseases and diabetes has the most evidence to support it. There is also a large literature base that shows a relationship between periodontal disease and atherosclerotic diseases including heart disease and stroke.^5,6 The association between atherosclerotic disease and periodontal disease was recently recognized by our medical colleagues in a joint publication on this subject which appeared in the Journal of Periodontology and the American Journal of Cardiology.^7,8 In these papers, recommendations for co-management by physicians and dentists are given.

Data also exist on a link to respiratory infections.^9,10 This relationship is found so far mainly in patients who are institutionalized, such as in intensive care units and nursing homes, where there is reduced ability to perform good oral hygiene. These patients are susceptible to pneumonia and bronchitis. However, these lower respiratory infections can be prevented by good oral hygiene, usually requiring assistance by staff who apply antiplaque mouth – rinses or swabs daily.

The results of the low birth weight and periodontal disease association studies are mixed and demonstrate that we still do not understand this relationship fully.^11-13 Two large periodontal intervention for reducing adverse pregnancy events trials have been published. The results suggest that periodontal intervention appears to have little effect in reducing adverse pregnancy outcomes as evaluated in these studies.^10,12 However, the trials are not definitive likely since they looked at young women who generally don’t have much periodontitis to start with and because the efficacy of the treatments provided in the studies was questionable. This field is still in flux and more studies using subjects who have clear periodontal disease, treatments that are effective, and adverse pregnancy outcomes shown to be strongly related to periodontal disease are needed.

A field that is showing some preliminary evidence is a link between periodontal diseases and cancer—particularly oral cancer and pancreatic cancer. Research in this area is just beginning. These early association studies are difficult to interpret because of the multitude of cofactors that need to be considered such as the role of tobacco use in both oral and pancreatic cancers. One study, however, did find an association between periodontitis and pancreatic cancer even in nonsmokers, which gives more credence to the idea that there is an association.¹⁴

What is still needed is an understanding of the biologic plausibility of these associations. What are the pathways that explain linkages? In diabetes we have much information on the potential mechanisms whereby periodontal tissue is susceptible to infection in people who have diabetes. Systemic inflammation may link the two diseases. In cancer, we haven’t identified the mechanisms that show the connection, although there are several theories. One is that cancer is enhanced by inflammation and periodontal infection causes inflammation. There are cancers that illustrate this relationship, such as gastric cancer, which is preceded by Helicobacter pylori infection of the antrum. This infection causes inflammation and eventually some of these patients develop stomach cancer. More research is needed to evaulate if there is truly an association between cancer and periodontal disease, and if so, to understand the mechanisms linking thise diseases.

Another area that merits attention is the relationship of periodontal diseases to Alz – heimer’s disease. The general thought is that periodontitis is an infection that leads to systemic inflammation, which increases the severity or incidence of chronic diseases like cardiovascular disease and diabetes, stroke, and possibly Alzheimer’s disease. Wherever a link may exist between systemic disease and systemic inflammation, researchers are taking a very close look at the disease associations that may result. This is an area of active investigation and shows much promise since inflammation can be managed by dietary supplements such as omega 3 fatty acids and drugs.

FUTURE MODEL OF CARE

Q. If evidence proves there is a link between periodontal diseases and cancer, how will this affect the provision of oral health care?

A. Dental professionals already play an important role in the detection of oral cancer. Oral cancer is a terrible disease in which the mortality rate has remained unchanged for decades, and part of the reason is detection of the cancer is too often at later stages when therapy is less successful. Oral cancer detection early in the process is an essential goal of oral care. The dental profession has an opportunity to make a large difference by more effective early detection and management of oral cancer.

In diseases where the link is already wellestablished, I believe the incorporation of periodontal management into overall health care is imminent. There is emerging evidence that the management of periodontal diseases in people who have diabetes will actually reduce not only glycated hemoglobin but also moderate the complications associated with diabetes such as heart disease and diabetic nephropathy.¹⁵ Eventually, I predict management of periodontal disease will become essential in the care of people who have diabetes just as foot and eye care are today. We haven’t reached this point yet. I believe the motivating factors that will lead to the dental office expanding its reach of care to include emerging evidence for effectiveness of dental office screening, data from insurance companies that show oral care often reduced medical care expenses, and advocacy by the profession.

REFERENCES

1. Cianciola LJ, Genco RJ, Patters MR, McKenna J, van Oss CJ. Defective polymorphonuclear leuko-cyte function in a human periodontal disease. Nature. 1977;265:445-447.
2. Naqshbandi M, Harris SB, Esler JG, Antwi-Nsiah F. Global complication rates of type 2 diabetes in Indigenous peoples: A comprehensive review. Diabetes Res Clin Pract. 2008;82:1-17.
3. Nelson RG, Shlossman M, Budding LM, et al. Periodontal disease and NIDDM in Pima Indians. Diabetes Care. 1990;13:836-840.
4. Taylor GW, Burt BA, Becker MP, et al. Severe periodontitis and risk for poor glycemic control in patients with non-insulin-dependent diabetes mellitus. J Periodontol. 1996;67(10 Suppl):1085-1093.
5. Genco RJ, Glurich I, Haraszthy V, Zambon J, DeNardin E. Overview of risk factors for periodontal disease and implications for diabetes and cardiovascular disease. Compend Contin Educ Dent. 2001;22(2 Spec No):21-23.
6. Oe Y, Soejima H, Nakayama H, Fukunaga T, et al. Significant association between score of periodontal disease and coronary artery disease. Heart Vessels. 2009;24:103-107.
7. Friedewald VE, Kornman KS, Beck JD, et al. The American Journal of Cardiology and Journal of Periodontology Editors’ Consensus: Periodontitis and Atherosclerotic Cardiovascular Disease. Am J Cardiol. 2009;104:59-68.
8. Friedewald VE, Kornman KS, Beck JD, et al. The American Journal of Cardiology and Journal of Periodontology Editors’ Consensus: Periodontitis and Atherosclerotic Cardiovascular Disease. J Periodontol. 2009;80:1021-1032.
9. Gomes-Filho IS, Santos CM, Cruz SS, et al. Periodontitis and nosocomial lower respiratory tract infection: preliminary findings. J Clin Periodontol. 2009;36:380-387.
10. Azarpazhooh A, Leake JL. Systematic review of the association between respiratory diseases and oral health. J Periodontol. 2006;77:1465-1482.
11. Vettore MV, Leal M, Leão AT, et al. The relationship between periodontitis and preterm low birth-weight. J Dent Res. 2008;87:73-78.
12. Radnai M, Pál A, Novák T, Urbán E, Eller J, Gorzó I. Benefits of periodontal therapy when preterm birth threatens. J Dent Res. 2009;88:280-284.
13. Vettore MV, Leão AT, Leal Mdo C, Feres M, Sheiham A. The relationship between periodontal disease and preterm low birthweight: clinical and microbiological results. J Periodontal Res. 2008;43:615-626.
14. Michaud DS, Liu Y, Meyer M, Giovannucci E, Joshipura K. Periodontal disease, tooth loss, and cancer risk in male health professionals: a prospective cohort study. Lancet Oncol. 2008;9:550-558.
15. Taylor GW, Borgnakke WS. Periodontal disease: associations with diabetes, glycemic control and complications. Oral Dis. 2008;14:191-203.

From Dimensions of Dental Hygiene. March 2010; 8(3): 22, 24.