Oral-Systemic Health

While the idea that oral bacteria may contribute to disease in other parts of the body has been discussed since at least the late 19th century,¹ for the last several decades a number of systemic diseases have been associated with oral health, particularly cardiovascular diseases and diabetes.^2-5 There are two mechanisms which have been hypothesized to explain the observed associations. Firstly, chronic inflammation in the oral cavity may increase levels of inflammatory markers in the bloodstream affecting immune response, or adding to the body’s general burden of disease. Secondly, the oral cavity may act as a reservoir for pathogenic bacteria that can enter the bloodstream and affect distant-site or systemic pathologies (systemic endotoxemia or bacteremia).

In 2000, the Surgeon General issued a report on the status of oral health in the US, recognizing an association between periodontal diseases and cardiovascular health, stroke, diabetes, and adverse pregnancy outcomes, and calling for more research to determine whether causation may be established.^{4, 5} Despite the lack of evidence of a causal link between periodontal disease and other system health concerns, the report emphasized that “oral health is integral to general health. You cannot be healthy without oral health.”⁴

In 2006, a series of articles in a JADA supplement addressed the association of periodontal disease to diabetes,³ cardiovascular health,² pregnancy outcomes,⁶ and pneumonia.⁷ The body of research has grown since then, and while the links between oral and systemic health have become more clear, it remains difficult to ascribe causality.^{8, 9}

Do these relationships tell us about causality or intervention?

While significant associations between oral health status and a number of systemic diseases have been established, the current evidence of these relationships is largely based on observational (i.e., case-control, cohort, and cross-sectional) studies.^{10, 11} Associations based on observational studies do not imply causation and may be biased by confounding factors, because “any association could potentially be due to another factor that influences both conditions.”¹²

Periodontal disease is common,¹³ with prevalence of about 42% of adults 30 years or older having some type of periodontitis.¹⁴ Similarly, according to the Centers for Disease Control and Prevention (CDC), about 47% of Americans have at least one risk factor for heart disease, such as diabetes, obesity, poor diet, alcohol abuse, or smoking.¹⁵ There is a significant overlap between factors seen to increase risk of periodontal disease and heart disease. People who smoke are not only at increased risk of gum disease, they have a higher risk for heart disease and stroke, as well as lung and other cancers.¹⁶ In addition, babies born to women who smoke are at increased risk of being low birth weight.¹⁷ Two or more diseases occurring in the same person, commonly referred to as comorbidities, may result from the same influencing factor, for example, smoking; people who smoke are at higher risk for heart disease and stroke, as well as gum disease.^{8, 9, 18}

Although a number of studies control for confounding factors and have found independent associations between periodontal and systemic diseases, establishing causality remains elusive, and the efficacy of periodontal treatment on a systemic condition cannot be posited without interventional studies and randomized clinical trials. Without such evidence, implying that periodontal treatment may reduce risk of a systemic disease “would be incorrect and misleading.”¹⁹ As stated in a 2013 editorial in JADA, “telling our patients that periodontal infections cause a plethora of nonoral diseases and conditions cannot be supported by existing evidence.”¹² At this time there is insufficient evidence that periodontal treatment should be encouraged or provided solely on the basis of preventing future onset of any systemic disease.

Gingivitis is very common among children, affecting approximately 70% of pediatric patients.^{20, 21} Generalized periodontitis in prepubescent children, however, can be a manifestation of a systemic disease (e.g., congenital or hematological). Referring a child with generalized periodontitis to a physician may help determine whether the periodontitis is a manifestation of a systemic disease.^20-24 As seen in the table, periodontal disease manifest in a child may be the sentinel symptom of a more serious condition.

Whether the periodontal symptoms are plaque-induced or systemic, early diagnosis and treatment is essential, although the success of periodontal therapy may be inhibited by systemic disease.²⁵ Delaying treatment of periodontal disease in children to facilitate differential diagnosis may increase the risk of bone loss.

Table. Examples of systemic and congenital conditions associated with periodontal disease in children and adolescents.^{21, 23, 26}

	Healthy bone (no alveolar bone loss)	Diseased bone (alveolar bone loss)
Healthy Gingiva (pink, firm, stippled)		Dentin dysplasia type I Hypophosphatasia** Inconclusive pediatric periodontal disease (LJP)* Post-avulsion/extraction
Diseased gingiva (erythematous, hemorrhagic)	Acrodynia Acute necrotizing ulcerative gingivitis (ANUG) Aplastic anemia Coxsackie virus (groups A and B) Eruption-related gingivitis Gingivitis Gingival fibromatosis Herpetic gingivostomatitis HIV Leukemia (AML / ALL) Mononucleosis (Epstein-Barr)  Minimally attached gingiva Mouthbreathing gingivitis Thrombocytopenia Vitamin C deficiency Vitamin K deficiency	Diabetes mellitus* Down syndrome* Inconclusive pediatric periodontal disease (LJP)* Langerhans cell histiocytosis X*** Neutrophil qualitative defect (leukocyte adhesion deficiency)* Neutrophil quantitative defect+* Papillon-Lefevre disease* Chediak-Higashi disease* Chronic granulomatous disease* Tuberculosis* Ehlers-Danlos syndrome (Type VIII)* Osteomyelitis*

+ including agranulocytosis, cyclic neutropenia, chronic idiopathic neutropenia
* work-up requires bacteriological culture and sensitivity
** work-up requires tooth biopsy
*** work-up requires gingival biopsy

1. Barnett ML. The oral-systemic disease connection. An update for the practicing dentist. J Am Dent Assoc 2006;137 Suppl:5S-6S.
2. Demmer RT, Desvarieux M. Periodontal infections and cardiovascular disease: the heart of the matter. J Am Dent Assoc 2006;137 Suppl:14S-20S; quiz 38S.
3. Mealey BL. Periodontal disease and diabetes. A two-way street. J Am Dent Assoc 2006;137 Suppl:26S-31S.
4. Oral health in America: a report of the Surgeon General. J Calif Dent Assoc 2000;28(9):685-95.
5. U.S. Public Health Service. Oral Health in America: A Report of the Surgeon General (Executive Summary). Washington, DC: Department of Health and Human Services 2000. Accessed April 5, 2018.
6. Bobetsis YA, Barros SP, Offenbacher S. Exploring the relationship between periodontal disease and pregnancy complications. J Am Dent Assoc 2006;137 Suppl:7S-13S.
7. Scannapieco FA. Pneumonia in nonambulatory patients. The role of oral bacteria and oral hygiene. J Am Dent Assoc 2006;137 Suppl:21S-25S.
8. Barnett ML, Hyman JJ. Challenges in interpreting study results: the conflict between appearance and reality. J Am Dent Assoc 2006;137 Suppl:32S-36S.
9. Lockhart PB, Bolger AF, Papapanou PN, et al. Periodontal disease and atherosclerotic vascular disease: does the evidence support an independent association?: a scientific statement from the American Heart Association. Circulation 2012;125(20):2520-44.
10. Batty GD, Jung KJ, Mok Y, et al. Oral health and later coronary heart disease: Cohort study of one million people. Eur J Prev Cardiol 2018;25(6):598-605.
11. Papapanou PN, Trevisan M. Periodontitis and atherosclerotic vascular disease: what we know and why it is important. J Am Dent Assoc 2012;143(8):826-8.
12. Borgnakke WS, Glick M, Genco RJ. Periodontitis: the canary in the coal mine. J Am Dent Assoc 2013;144(7):764-6.
13. 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(1):59-68.
14. Eke PI, Thornton-Evans GO, Wei L, et al. Periodontitis in US Adults. The Journal of the American Dental Association 2018;149(7):576-88.e6.
15. Centers for Disease Control and Prevention. Heart Disease Facts. 2017. Accessed 15 May 2018.
16. National Cancer Institute. Risk Factors for Cancer. 2015. Accessed 15 May 2018.
17. Bernabe E, MacRitchie H, Longbottom C, Pitts NB, Sabbah W. Birth Weight, Breastfeeding, Maternal Smoking and Caries Trajectories. J Dent Res 2017;96(2):171-78.
18. Ganesan SM, Joshi V, Fellows M, et al. A tale of two risks: smoking, diabetes and the subgingival microbiome. ISME J 2017;11(9):2075-89.
19. Pihlstrom BL, Hodges JS, Michalowicz B, Wohlfahrt JC, Garcia RI. Promoting oral health care because of its possible effect on systemic disease is premature and may be misleading. J Am Dent Assoc 2018;149(6):401-03.
20. Oh TJ, Eber R, Wang HL. Periodontal diseases in the child and adolescent. J Clin Periodontol 2002;29(5):400-10.
21. Pari A, Ilango P, Subbareddy V, Katamreddy V, Parthasarthy H. Gingival diseases in childhood - a review. J Clin Diagn Res 2014;8(10):ZE01-4.
22. Kumar A, Masamatti SS, Virdi MS. Periodontal diseases in children and adolescents: a clinician's perspective part 2. Dent Update 2012;39(9):639-42, 45-6, 49-52.
23. Meyle J, Gonzales JR. Influences of systemic diseases on periodontitis in children and adolescents. Periodontol 2000 2001;26:92-112.
24. Berglundh T, Wellfelt B, Liljenberg B, Lindhe J. Some local and systemic immunological features of prepubertal periodontitis. J Clin Periodontol 2001;28(2):113-20.
25. Califano JV, Research S, Therapy Committee American Academy of P. Position paper: periodontal diseases of children and adolescents. J Periodontol 2003;74(11):1696-704.
26. Al-Ghutaimel H, Riba H, Al-Kahtani S, Al-Duhaimi S. Common periodontal diseases of children and adolescents. Int J Dent 2014;2014:850674.

Oral Health Topics

• Cancer (Head and Neck)
• Diabetes
• Hypophosphatasia and X-Linked Hypophosphatemia
• Nutrition and Oral Health
• Pregnancy

ADA Catalog
The patient education brochures listed below can be ordered online through the ADA Catalog:

• Healthy Mouth, Healthy Body: Making the Connection (W203)
• Diabetes and Your Oral Health (W604)

For the Patient
For the Dental Patient is a JADA column that is geared toward patient education and intended to facilitate discussion between dentists and patients.

• What is Gum Disease? (January 2011) (PDF)
• Diabetes: Tips for Good Oral Health (July 2010) (PDF)
• Healthy Mouth, Healthy Body (April 2006) (PDF)

Professional Resources
Search JADA for articles related to systemic health
ADA Library Services

American Academy of Periodontology

• Gum Disease and other Systemic Diseases
• Periodontal Disease and Systemic Health

American Academy of Pediatric Dentistry
Oral Health Policies & Recommendations (The Reference Manual of Pediatric Dentistry)

• Classification of Periodontal Diseases in Infants, Children, Adolescents, and Individuals with Special Health Care Needs
• Periodontal Diseases of Children and Adolescents
• Guidelines for Periodontal Therapy
• Treatment of Plaque-induced Gingivitis, Chronic Periodontitis, and Other Clinical Conditions