Written by Herbert I. Bader, DDS Saturday, 31 March 2007 19:00
The oral/systemic connection has become the most overwhelmingly published topic in the dental literature within the past few years, and it is now spilling over into the medical literature as well. The vast majority of studies reported are related to inflammatory periodontal disease and its causal links to a panoply of systemic conditions. Thousands of articles relate the chronic, infectious nature of periodontitis to heart disease, stroke, pulmonary dysfunction, preterm, low-birthweight babies, osteoporotic diseases, diabetes mellitus, and neuropathological syndromes such as Alzheimer’s disease. We must understand the limitations of these reports, put them into perspective, and be aware that as healthcare providers we share the responsibility for our patients’ medical health.1
Interest in the impact of oral health on systemic issues is not new, nor is the role of plaque (biofilm) as it relates to the pathogenesis of oral disease. Abulcasis wrote 1,000 years ago that “ye shall remove the encrustations from the teeth lest they be lost.” He had no concept of the importance of the immune response in generating the inflammatory component and its systemic sequelae, and he certainly had no sense of the term Porphyromonas gingivalis, yet he instinctively knew the importance of plaque control.
Illustration by Nathan Zak
We have come far since those early insights. Armed today with the glimmer of understanding regarding the nature of the complex interplay of our bodies’ systems, we can begin to unravel these mysteries and develop effective management protocols.
About 2 decades ago the literature began to fill with both retrospective and proof of concept studies relating oral diseases, mainly periodontitis, to atherosclerotic changes and subsequent cardiovascular disease (CVD).2,3 The developing paradigm of the inflammatory nature of coronary disease, along with the similar observations relating to periodontal disease, forced investigators to look at the commonality of these conditions.4-7 In 1999 a 21-year study showed a two-fold increase in chronic heart disease in patients with gingivitis and periodontitis, as contrasted with periodontally healthy controls.8
The inflammatory nature of periodontal infection invokes both local and systemic immune responses,9 with many intermediate metabolites as part of the immune cascade. One of these is C-reactive protein (CRP), which is a product of the inflammatory cascade and is considered to be a marker of inflammation. It is elevated in the untreated periodontal patient.10,11 Numerous studies link the acute phase inflammatory response to periodontal disease with other systemic entities, such as heart disease.12-14 It has been postulated that a genetic predisposition for periodontitis15 resulting in an exaggerated response to inflammatory stimuli may be one of the mechanisms linking periodontal disease to CVD. This hyperproduction of CRP has been demonstrated in periodontal disease and linked to increased risk for CVD.16
One of the areas of interest in the ongoing search for causal links is the observation that CVD and periodontitis share many common risk factors. Age, gender, smoking, socioeconomic status, and diabetes are the most common. There are studies that show dyslipidemias (abnormal cholesterol levels) may be included in this list.17,18 The fact that both periodontal disease and atherosclerosis leading to CVD are both inflammatory phenomena resulting from the response to chronic infection and its sequelae is of great interest. Periodontopathic bacteria may be directly or indirectly involved in atherosclerotic disease.19,20 The significance of common risk factors has been nicely demonstrated in a recent study showing a positive association between periodontal disease and CVD in a homogeneous Danish population.21 The entity of acute coronary syndrome (ACS) has been linked with periodontitis, in that the increased oral bacterial load of periodontal pathogens such as P. gingivalis, Tannerella forsythensis, and Treponema denticola may well be concomitant risk factors in the development of ACS.22
There is an apparent relationship between poor dental health and cerebrovascular ischemic stroke, which is the third leading cause of death after CVD and cancer.22-27 Again, the links relate to the nature of the immune response to inflammatory stimuli.
The literature is replete with studies relating periodontal disease to diabetes in a 2-way relationship. Diabetes increases the risk of periodontitis. This has been demonstrated with many biologically plausible mechanisms.28-32 Studies support the fact that the brittle diabetic is much more likely to have a glycemic event in the presence of untreated periodontal infection.33 The presence of periodontitis increases the risk of worsening of glycemic control over time.34 Conversely, blood glucose levels can be favorably affected by periodontal treatment. There is mounting evidence that maintenance of the susceptible periodontal patient goes hand-in-hand with controlling the diabetic state.35,36
Along with the link to CVD and diabetes are numerous studies on the association between chronic obstructive pulmonary disease and periodontitis. Again the inflammatory response of the immune system may be the common factor.37-39 The co-existence of infection, inflammation, and immunologic mediators may hold the keys to ongoing and future studies in this area.
Dr. Marjorie Jeffcoat and her group conducted a landmark proof of concept study in 200340 in which they showed that conservative periodontal therapy (scaling and root planing) reduced the incidence of low-birthweight, preterm infants. This is another area of systemic risk associated with periodontal disease. This and other studies41-43 have provided sufficient evidence to induce CIGNA Insurance Company to announce 100% coverage for scaling and root planing during pregnancy, as part of the CIGNA Dental Oral Health Maternity Program.
Numerous additional reports appear in the literature proposing links between oral disease and various systemic entities. These include rheumatoid arthritis,44 osteoporosis,45 and cirrhosis of the liver.46 Gerontologists in association with researchers in geriatric medicine are looking at all sorts of intriguing links, such as dental caries, periodontal disease, and cardiac arrythmias.47 There is considerable current interest in the possible bidirectional relationship between periodontal disease and Alzheimer’s disease. Some of the proposed mechanisms include metastatic spread of periodontal pathogens to the brain, brain injury secondary to inflammatory mediators released by the immune system in response to periodontal pathogens, and others.48-50
We are on the threshold of identifying the causal links between all the life-threatening entities discussed here. We may not yet know the specific relationships, but we do know that prevention and treatment of chronic inflammatory disease such as periodontitis can significantly improve systemic health. This is becoming an increasingly important issue as we deal with the dynamics of an aging population.
The maintenance of oral health is certainly becoming the focus of both dental and medical health delivery and management paradigms. Insurance providers such as CIGNA and Delta are developing products to encourage early intervention and recare compliance for periodontal patients. The beneficial effects of good oral health are being seen in large ongoing studies, such as the Aetna-Columbia University study of 145,000 subscribers. Medical care for patients with chronic diseases such as diabetes and CVD was shown to be significantly lower if they received periodontal care. It has been stated that “Preventive periodontal management will pay huge dividends as the population ages with regard to reducing potential systemic complications, especially those associated with chronic inflammation.”51
In line with the recorded literature, one study took a 15-year retrospective look of the records of 200 patients. The records suggested better health with fewer systemic problems in the compliant co-horts who maintained good oral hygiene and reasonable recare intervals.52 The number of records reviewed was not statistically viable, but did indicate a trend now recognized as significant in the area of oral health and overall well-being.
The importance of oral health maintenance to prevent or ameliorate systemic disease is well-established. The compliant periodontal patient is systemically healthier. The emergence of transdisciplinary paradigms for improving and maintaining patient health is the next, im-mediate thrust of healthcare providers.
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13. Choi JL, Chung SW, Kang HS, et al. Establishment of Porphyromonas gingivalis heat-shock-protein-specific T-cell lines from atherosclerosis patients. J Dent Res. 2002;81:344-348.
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15. Kornman K, Duff G, Reilly P. Re: A critical assessment of interleukin-1 (IL-1) genotyping when used in a genetic susceptibility test for severe chronic periodontitis. J Periodontol. 2002;73:1553-1556. [comment on: Greenstein G, Hart TC. J Periodontol. 2002;73:231-247.]
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17. Losche W, Karapetow F, Pohl A, et al. Plasma lipid and blood glucose levels in patients with destructive periodontal disease. J Clin Periodontol. 2000;27:537-541.
18. Katz J, Flugelman MY, Goldberg A, et al. Association between periodontal pockets and elevated cholesterol and low density lipoprotein cholesterol levels. J Periodontol. 2002;73:494-500.
19. Chiu B. Multiple infections in carotid atherosclerotic plaques. Am Heart J. 1999;138(5 pt 2):S534-S536.
20. Slade GD, Offenbacher S, Beck JD, et al. Acute-phase inflammatory re-sponse to periodontal disease in the US population. J Dent Res. 2000;-79:49-57.
21. Geismar K, Stoltze K, Sigurd B, et al. Periodontal disease and coronary heart disease. J Periodontol. 2006;77:1547-1554.
22. Renvert S, Pettersson T, Ohlsson O, et al. Bacterial profile and burden of periodontal infection in subjects with a diagnosis of acute coronary syndrome. J Periodontol. 2006;77:1110-1119.
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24. Syrjanen J, Peltola J, Valtonen V, et al. Dental infections in association with cerebral infarction in young and middle-aged men. J Intern Med. 1989;-225:179-184.
25. Grau AJ, Buggle F, Heindl S, et al. Recent infection as a risk factor for cerebrovascular ischemia. Stroke. 1995;26:373-379.
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27. Janket SJ, Baird AE, Chuang SK, et al. Meta-analysis of periodontal disease and risk of coronary heart disease and stroke. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003;95:559-569.
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33. 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(suppl):1085-1093.
34. Thorstensson H, Kuylensteirna J, Hugoson A. Medical status and complications in relation to periodontal disease experience in insulin-dependent diabetics. J Clin Periodontol. 1996;23(3 pt 1):194-202.
35. Grossi SG, Skrepcinski FB, DeCaro T, et al. Response to periodontal therapy in diabetics and smokers. J Periodontol. 1996;67(suppl):1094-102.
36. Faria-Almeida R, Navarro A, Bascones A. Clinical and metabolic changes after conventional treatment of type 2 diabetic patients with chronic periodontitis. J Periodontol. 2006;77:591-598.
37. Azarpazhooh A, Leake JL. Systematic review of the association between respiratory diseases and oral health. J Periodontol. 2006;77:1465-1482.
38. Garcia RI, Nunn ME, Vokonas PS. Epidemiologic associations between periodontal disease and chronic obstructive pulmonary disease. Ann Periodontol. 2001;6:71-77.
39. Terpenning MS. The relationship between infections and chronic respiratory diseases: an overview. Ann Periodontol. 2001;6:66-70.
40. Jeffcoat MK, Hauth JC, Geurs NC, et al. Periodontal disease and preterm birth: results of a pilot intervention study. J Periodontol. 2003;74:1214-1218.
41. Lopez NJ, Da Silva I, Ipinza J, et al. Periodontal therapy reduces the rate of preterm low birth weight in women with pregnancy-associated gingivitis. J Periodontol. 2005;76(suppl):2144-2153.
42. Bosnjak A, Relja T, Vucicevic-Boras V, et al. Pre-term delivery and periodontal disease: a case-control study from Croatia. J Clin Periodontol. 2006;33:710-716.
43. Radnai M, Gorzo I, Urban E, et al. Possible association between mother’s periodontal status and preterm delivery. J Clin Periodontol. 2006;33:791-796.
44. Mercado FB, Marshall RI, Bartold PM. Inter-relationships between rheumatoid arthritis and periodontal disease: a review. J Clin Periodontol. 2003;30:761-772.
45. Persson RE, Hollender LG, Powell LV, et al. Assessment of periodontal conditions and systemic disease in older subjects. I. Focus on osteoporosis. J Clin Periodontol. 2002;29:796-802.
46. Movin S. Relationship between periodontal disease and cirrhosis of the liver in humans. J Clin Periodontol. 1981;8:450-458.
47. Holm-Pedersen P, Avlund K, Morse DE, et al. Dental caries, periodontal disease, and cardiac arrythmias in community-dwelling older persons aged 80 and older: Is there a link? J Am Geriatr Soc. 2005;53:430-437.
48. Kondo K, Niino M, Shido K. A case-control study of Alzheimer’s disease in Japan: significance of life-styles. Dementia. 1994;5:314-326.
49. Gatz M, Mortimer JA, Fratiglioni L, et al. Potentially modifiable risk factors for dementia in identical twins. Alzheimer’s & Dementia. 2006;2:110-117.
50. Stein PS, Scheff S, Dawson DR III. Alzheimer’s disease and periodontal disease: mechanisms underlying a potential bi-directional relationship. Grand Rounds Oral-Sys Med. Sep 2006;1:14-24.
51. Iacopino AM. Maintaining oral health in the aging population: the importance of the periodontal-systemic connection in the elderly. Grand Rounds Oral-Sys Med. Sep 2006;1:25-37.
52. Bader HI. Fifteen-year retrospective periodontal re-care study: manual vs powered toothbrush (In press). J Dent Res, Abstract No. 5203. 2007.
Dr. Bader practices periodontics and implant dentistry in Concord, Mass. He is a graduate of New York University College of Dentistry, and in 1966 completed a residency in periodontology at the Harvard School of Dental Medicine, where he currently serves as lecturer in postgraduate periodontology. He is a Fellow of the American College of Dentists, International College of Dentists, and American Academy of Osseointegration. He has been published in the Journal of Dental Research, Journal of Periodontology, Journal of Clinical Periodontology, and the American Journal of Dentistry. He can be reached at (978) 369-5066 or by visiting drbaderimplants.com.
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