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Chemotaxis: Movement of cells in response to a chemical stimulus. The movement of neutrophils to the site of injury or inflammation.
Cytokines: Chemicals that are involved in growth regulation. They influence both bone resorption and bone formation.
Endotoxin: Bacterial toxin confined within the body of a bacterium, freed only when the bacterium is broken down.
Etiology: Study of the causes of disease.
Fibrinogen: Clotting factor.
Fibroblast: Any cell or corpuscle from which connective tissue is developed.
Hematogenesis: The development of blood cells.
Host: Organism on which a parasite lives.
Mediator: May be a nerve, a chemical substance, or a cellular substance.
Pathogens: Anything capable of producing disease.
Pulmonary: Pertaining to the lungs
Spirometry: Measurement of air capacity of the lungs.
Inflammation represents the body’s protective response to injury and tissue destruction. This response consists of a spectrum of highly coordinated events that occur at the cellular and tissue level. Its purpose is to destroy, dilute, or sequester the injurious agent and the injured tissues in order to permit healing. Inflammation is a defensive mechanism intended to protect the host, but can also be harmful. Clinical signs of inflammation are redness due to open blood vessels, heat due to warmth of blood, swelling due to edema, pain due to stimulation of pain receptors, and loss of function due to edema.1
Periodontitis is the inflammation of the periodontium (gingiva and underlying connective tissue), resulting in features such as clinical attachment loss, alveolar bone loss, and periodontal pocketing. In periodontitis, one can see enlargement or recession of the gingivae, bleeding on probing, increased tooth mobility, drifting of teeth, and/or tooth exfoliation. Chronic periodontitis is a slowly progressing process that may occur continuously or in bursts of activity. Histologically, the gingival tissue from chronic periodontitis displays junctional epithelium more apical to the cemento-enamel junction, loss of collagen fibers subjacent to the pocket epithelium, bone loss, numerous neutrophils (polymorphonuclear cells [PMNs]), and dense inflammatory cell infiltrate with plasma cells, lymphocytes, and macrophages.2
Tissue damage in chronic periodontitis is the result of major inflammatory and immunopathologic components activated by the host response. These include alteration of fibroblast function, activation of macrophages to release collagenase and other lytic enzymes, activation of lymphocytes, modulation of fibroblast growth, collagen synthesis, and stimulation of bone resorption. Prostaglandins and cytokines appear to be critically involved in tissue destruction caused by periodontitis.2
Researchers have suggested that the primary cause of periodontitis is a bacterial infection. Gingival inflammation is the result of plaque, or bacterial biofilm, which contains Gram-negative bacteria such as Porphyromonas gingivalis, Bacteroides forsythus, and Prevotella intermedia, among many others.2 These bacteria possess complex carbohydrates and proteins on their cell wall, called endotoxins or lipopolysaccharides (LPSs). When these molecules are detected by the host, a protective response ensues, resulting in inflammation, recruitment of white blood cells (WBCs), and release of cytokines and chemical mediators. The chemical mediators that cause the main systemic problems are interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor-necrosis factor-alpha (TNF-α). The function of IL-1 is to recruit osteoclasts (bone-resorbing cells), which remove bone matrix. The function of IL-6 is to increase fibrinogen, which helps in the clotting mechanism of injured blood vessels. The function of TNF-α is to primarily increase the amount of C-reactive proteins (CRPs), which recruit more macrophages to the site of injury. These mediators, although helpful in fighting insult to the body, can be harmful as well.
Periodontitis has been linked with a number of systemic diseases, such as cardiovascular disease, diabetes mellitus, respiratory disease, and osteoporosis. The following article explores the connections and evidence.
Periodontitis and Cardiovascular Disease
Atherosclerosis is the thickening and hardening of arteries due to plaque buildup on arterial walls. This is a chronic inflammatory condition that affects injured arteries. Growing evidence suggests infectious agents are causing this injury, thereby resulting in this chronic inflammation. This chronic inflammatory response increases the circulation of mediators such as CRPs and fibrinogen. Inflammation and atherosclerosis have a link, which suggests that chronic infections, such as chronic periodontitis, may predispose someone to cardiovascular disease or exacerbate existing cardiovascular disease (CVD). The following is suggested regarding inflammatory mediators common in chronic periodontitis and CVD3:
• C-reactive proteins: found in chronic periodontitis and increased levels in the blood will damage the smooth muscles of blood vessels and collection of macrophages.
• IL-1: found in association with increased risk for severe periodontitis and inside atherosclerotic plaques.
• TNF-α: also found in chronic periodontal infections. Systemically, it increases the synthesis of triglycerides from the liver. An elevated triglyceride level is associated with lowered “good lipids,” known as high-density lipoproteins (HDL). This is associated with coronary heart disease (CHD).
• Fibrinogen: synthesized by the liver due to elevation of IL-6. The IL-6 level is also high in chronic periodontitis. Fibrinogen is a clotting factor that is common in creating thrombi (clots) in the blood vessels, resulting in myocardial infarction (MI; heart attack) and cerebral vascular accident (stroke).3
Similarities in the pathogenesis of atherosclerosis and periodontitis have suggested a common underlying biological mechanism for the two conditions. Most evidence supporting a relationship between chronic periodontitis and CVD is from studies performed in the late 1980s and continued since then, associating patients with a history of MI with poorer oral health than control subjects. Those with acute MI had poorer oral health than those who were healthy.8 The incidence of mortality and CHD increased as the severity of periodontal disease increased.9 Patients with a 20% increase in periodontal bone loss had a 40% increase in developing chronic heart disease (eg, nonfatal MI, angina pectoris, CHD deaths).4 P gingivalis has the ability to induce the oxidization of “bad lipids,” known as low-density lipoproteins (LDL), which are pathogenic for plaque formation on arterial walls.5,6 CRP levels in patients with chronic periodontitis fall in the same range as those who have cardiovascular disease.7 Gentle mastication can induce the release of endotoxins from the mouth into the bloodstream, especially in patients with severe periodontitis. Also, periodontal pockets are a chronic source of passage of pro-inflammatory bacterial components in the bloodstream.10 Periodontitis and gingivitis are independently associated with a risk for cerebral ischemia (stroke).11
Clinical manifestations of cardiovascular disease include hypertension (see above), fatigue after mild activity or when supine, ankle swelling, angina (chest pain), myocardial infarction, and cerebral vascular accident. It is essential that a thorough medical history and blood pressure be taken during initial oral examinations. If a patient answers affirmatively to any of the above, he/she may be taking medications or, in fact, be unaware of an existing condition. If the patient is not well-controlled or if any question exists regarding the patient’s health status, a medical consultation is essential. A patient with well-controlled hypertension, for example, will see the physician every 3 to 6 months. However, a general dentist should check the patient’s blood pressure at the initial examination and on a yearly basis.12
Chronic Periodontitis and Diabetes Mellitus
Diabetes mellitus is one of the most common diseases in the United States. It is a chronic metabolic disorder affecting carbohydrate, fat, and protein metabolism, possibly resulting in hyperglycemia. Two types of diabetes mellitus are as follows: Type I is caused by defective secretion of insulin, while Type II is a result of impaired insulin action due to tissue resistance. Appropriate measures can be taken to control blood glucose levels and prevent both acute and chronic complications.15
Patients with uncontrolled diabetes are prone to oral complications such as gingivitis, periodontal disease, fungal infections, and caries due to xerostomia. Uncontrolled diabetes also affects wound healing. However, those with controlled diabetes will heal similarly as the patient without diabetes. The most common oral symptom of diabetes is the increased prevalence and severity of periodontitis. Poorly controlled diabetes results in rapid progression of gingivitis and periodontitis. The degree of metabolic control and duration of diabetes are closely associated with the severity of periodontal disease.16
Components of Periodontal Disease Relating to Diabetes
The two components of periodontal disease are bacteria and host response. Periodontal disease and diabetes have a bidirectional relationship<sup>17-19</sup>:
• The presence of diabetes increases the prevalence, incidence, and severity of periodontitis.17,18
• Advanced glycation end products (AGE), which increase rapidly in poorly controlled diabetes, tend to transform important inflammatory cells into more destructive cells, thereby resulting in more damage to many parts of the body as well as to the periodontium.18
• Hyperglycemia results in impaired neutrophil chemotaxis. Neutrophils are the first cells in the host response against bacteria. Therefore, it can be concluded that the host response will be impaired during gingivitis and periodontitis.17-19
• Diabetes leads to a twofold to fourfold greater risk of severe bone loss. As glycemic control worsens, the effects of periodontal disease become greater.17
• Due to the high vascularity of acute periodontitis, the inflamed periodontium may serve as an endocrine-like source for TNF-α, which antagonizes the effects of insulin. Therefore, glycemic control can be improved with periodontal treatment in these patients.18
• Treatment of chronic periodontitis helps glycemic levels in some patients.17-19
The following has also been confirmed20:
• The severity of periodontal disease increases with the duration of diabetes.
• Periodontitis is an infection that is twice as prevalent in individuals with diabetes as in people without diabetes.
• Severe periodontal infections are much more common in Type II diabetes and can worsen the metabolic control of diabetes.
• The chronic nature of periodontal infection represents a greater long-term risk for the diabetic acute infections.
• P gingivalis is able to sustain systemic inflammation, which is another reason people with diabetes need to have their chronic periodontitis treated.
• The increased inflammatory and cytokine response seen in diabetes is responsible for the dysregulation of lipid metabolism, insulin resistance, and long-term microvascular complications. Chronic periodontitis could magnify the already elevated cytokine response and contributes to the overall burden of systemic inflammation.
• Mechanical periodontal therapy with adjunctive systemic doxycycline resulted in a 0.6% decrease in glycated hemoglobin.20
Clinical manifestations of poorly controlled or uncontrolled diabetes are mostly polyphagia (increased hunger), polydipsia (increased thirst), polyurea (increased urination), pruritis (itching), weakness, increased susceptibility to infections, xerostomia leading to dental caries, burning mouth or tongue, altered taste sensation, candidiasis and other opportunistic infections, and severe gingivitis and periodontitis. It should be a common practice to ask patients if diabetes runs in the family. It is essential for the dental clinician to look for these signs and consider referring the patient for a workup for diabetes.12
The primary methods used for diagnosing diabetes are examining blood glucose levels for short- or long-term control via the glycated hemoglobin test, or HbA1c test. This test is used because it monitors the patient’s long-term control (approximately 90 days due to the fact that red blood cells are replaced every 90 days). Consequently, the patient needs to be reassessed every 3 months for disease management. A normal value for the HbA1c test is 6.0% to 6.5%.14 Levels greater than 7.9% are indicative of poor control and will require the intervention of the patient’s physician. Antibiotic prophylaxis will be necessary for any emergency dental treatment in these patients with poorly controlled diabetes.12
Periodontal Inflammation and Respiratory Disease
The oral cavity has long been considered a potential reservoir for respiratory pathogens. Mechanisms of infection can be due to aspiration into the lungs of the oral pathogens capable of causing pneumonia. In patients in the hospital and in nursing homes, bacteria that colonize the teeth can potentially be aspirated into the lungs and can lead to pneumonia and decreased overall lung function, which is measured by spirometry.13
Oral microorganisms spreading into the lower respiratory tract can take two routes: hematogenous (via blood pathway) and aspiration. The hematogenous route is rare. However, aspiration is much more common. Aspiration of material from the upper airway occurred in 45% of healthy subjects and in 70% of subjects with impaired consciousness in one study. Periodontal disease and poor oral hygiene might result in a higher concentration of oral pathogens in the saliva, sufficient in amount to overwhelm local immune defenses. Dental plaque may also harbor colonies of pulmonary pathogens and promote their growth.13
The symptoms of chronic obstructive pulmonary disease (COPD) and pneumonia are difficulty breathing, chronic coughing up of phlegm, flu-like symptoms, and fatigue. If a patient presents with these symptoms, the dental professional should refer the patient to a physician for further workup.
Periodontitis and Osteoporosis
Osteoporosis is a debilitating metabolic bone disease that primarily affects elderly women. There is increasing evidence that osteoporosis and the underlying loss of bone mass is associated with periodontal disease and tooth loss. Current evidence, including several prospective studies, supports an association of osteoporosis and the onset and progression of periodontal disease in humans.21
Potential mechanisms by which host factors may influence the onset and progression of periodontal disease, directly or indirectly, include underlying low bone density in the oral cavity, bone loss as an inflammatory response to infection, genetic susceptibility, and shared exposure to risk factors.21
Some studies have suggested that hormone replacement therapy is associated with retention of more teeth in old age. Nutritional factors also play a role in modifying periodontal disease, such as adequate lifelong intake of vitamin D and calcium.22 Calcium is used for building strong bones and teeth. The mineral also helps with maintaining a normal heartbeat, conveying nerve signals, and releasing hormones. Vitamin D plays a major role in calcium absorption. The relationship between calcium absorption and vitamin D is similar to that of a locked door and a key. Vitamin D is the key that unlocks the door and allows calcium to leave the intestine and enter the bloodstream. Vitamin D also works in the kidneys to help reabsorb calcium that otherwise would be excreted.24
Systemic loss of bone density in osteoporosis, including that of the oral cavity, may provide a host system that is increasingly susceptible to the infectious destruction of periodontal tissue. Understanding this association will help health professionals provide improved means to prevent, diagnose, and treat this disease.21 Osteoporosis is more common in postmenopausal women not receiving hormone treatment. A person with osteoporosis may have a petite stature and common fractures in long bones. The diagnosis of osteoporosis can be via radiographs, symptomology, and blood workup. A common treatment for osteoporosis is hormone replacement with estrogen.12 However, due to concerns regarding a connection with breast cancer, medications such as bisphosphonates (eg, alendrolate) are being used. These medications prevent the action of osteoclasts. In addition, some evidence indicates that some medications used to treat osteoporosis can be helpful in the management of periodontal disease.21,22
Controlling Oral Inflammation
Inflammation is a protective process to fight injury and infection. While its purpose is to help in healing and removal of infection, its actions can be harmful. Therefore, it is important that a patient maintain good oral hygiene. Dental professionals realize that this is not an easy task for most patients to accomplish on their own. Compliance with oral hygiene regimens can be time-consuming, and many patients may lack the dexterity required to effectively remove plaque from all surfaces.
In order to fight oral inflammation, mechanical removal of pathogens via scaling and root planing in a diseased sulcus/pocket is important. Therefore, a prophylaxis/periodontal maintenance schedule based on the patient’s needs (not insurance status) must be recommended. Locally applied antimicrobials (LAA), such as PerioChip®, Dexcel Pharma Technologies, www.dexcel.com), Arestin® (OraPharma, www.orapharma.com), and Atridox® (DenMat, www.denmat.com), can be beneficial in periodontal pockets 5 mm or more in depth. These products can release medication into the periodontal pockets for a period, reducing the bacterial/inflammatory challenge and creating an environment for better healing.
To increase the effectiveness of patient home care, additional therapies are recommended. One option is the inclusion of an antimicrobial/anti-inflammatory toothpaste that contains triclosan with a copolymer (Colgate® Total®, Colgate Palmolive, www.colgate.com/en/us/oc/). Triclosan kills bacteria by interfering with the enzyme necessary for fatty-acid synthesis.23 In addition, triclosan works directly on the inflammation process by directly inhibiting potent inflammatory mediators. Adding an antimicrobial in this fashion offers benefit without an additional step and therefore reduces compliance as an issue. Another means of adding an antimicrobial is in the form of a mouth rinse.
Chlorhexidine gluconate is a broad-spectrum antiseptic antimicrobial. It can be used as a rinse to prevent gingivitis by reducing and inhibiting the formation of plaque and as an LAA for the reduction of periodontal pockets (PerioChip). Because it is positively charged, it binds to the oral mucosa and bacterial biofilm for up to 12 hours (and longer based on the delivery system). For this reason, chlorhexidine is a highly effective adjunct therapy. Another rinse option is stannous fluoride, which acts as an antibacterial and inhibits the formation of plaque.
If periodontal health cannot be obtained through regular periodontal maintenance and good oral hygiene, then the patient should be referred to a periodontist. A patient should also be referred if he or she has diabetes or cardiovascular disease along with periodontal disease for management of periodontal inflammation.
Inflammation, although a protective process, can be harmful. Periodontitis is the result of inflammation to the periodontium, and cytokines, or chemical mediators, are the result of inflammatory cells fighting against bacterial plaque. High amounts of these mediators can affect the body’s systems, especially the arteries, and can cause more harm in a patient with compromised cardiovascular health. Dental professionals should include blood pressure screenings as part of their patient assessment practices and discuss heart-healthy strategies.
Dental professionals should assess risks for patients with diagnosed (or undiagnosed) diseases such as diabetes, respiratory diseases, and osteoporosis, and refer patients to a physician or periodontist as necessary.
It is very important to evaluate and monitor oral hygiene in at-risk patients. The inclusion of antimicrobials as a part of patient home care to enhance plaque control should also be considered.
1. Ramzi S, Contran SL, Robbins V, et al. Basic Pathology. 7th ed. New York, NY: Harcourt Publishers LTD; 2002.
2. Fleming T. 1999 International Workshop for Classification of Periodontal Diseases and Conditions. Ann Periodontol. 1999;4:32-35.
3. De Nardin E. The role of inflammatory and immunological mediators in periodontitis and cardiovascular disease. Ann Periodontol. 2001;6(1):30-40.
4. Beck J, Garcia R, Hass G, et al. Periodontal disease and cardiovascular disease. J Periodontol. 1996;67(10 suppl):1123-1137.
5. Kuramitsu HK, Qi M, Kang IC, Chen W. Role for periodontal bacteria in cardiovascular diseases. Ann Periodontol. 2001;6(1):41-47.
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8. Mattila KJ, Nieminen MS, Valtonen W, et al. Association between dental health and acute myocardial infarction. BMJ. 1989;298(6676):779-782.
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10. Geerts SO, Nys M, De MP, et al. Systemic release of endotoxins induced by gentle mastication: association with periodontitis severity. J Periodontol. 2002;73(1):73-78.
11. Dorfer CE, Becher H, Ziegler CM, et al. The association of gingivitis and periodontitis with ischemic stroke. J Clin Periodontol. 2004;31(5):396-401.
12. Little J. Dental Management of a Medically Compromised Patient. 6th ed. Philadelphia, PA: Elsevier Science Health Science div; 2002.
13. Mojon P. Oral health and respiratory infection. J Can Dent Assoc. 2002;68(6):340-345.
14. Piche JE, Swan RH, Hallmon WW. The glycosylated hemoglobin assay for diabetes: its value to the periodontist. Two case reports. J Periodontol. 1989;60(11):640-642.
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16. Ryan ME, Carnu O, Kamer A. The influence of diabetes on the periodontal tissues. J Am Dent Assoc. 2003;134:34S-40S.
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19. Iacopino AM. Periodontitis and diabetes interrelationships: role of inflammation. J Periodontol. 2001;6(1):125-137.
20. Grossi SG. Treatment of periodontal disease and control of diabetes: an assessment of the evidence and need for future research. Ann Periodontol. 2001;6(1):138-145.
21. Wactawski-Wende J. Periodontal diseases and osteoporosis: association and mechanisms. Ann Periodontol. 2001;6(1):197-208.
22. Krall EA. The periodontal-systemic connection: implications for treatment of patients with osteoporosis and periodontal disease. Ann Periodontol. 2001;1(6):209-213.
23. Cullinan MP, Westerman B, Hamlet SM, et al. The effect of triclosan-containing dentifrice on progression of periodontal disease in an adult population. J Clin Periodontol. 2003;30(5):414-419.
24. National Osteoporosis Foundation. www.nof.org/prevention/calcium.htm.
ABOUT THE AUTHORS
Richard Nejat, DDS
Dr. Richard Nejat received his Doctorate of Dental Surgery from New York University, where he graduated in the top of his class, receiving the prestigious OKU honors. Following graduation, Dr. Nejat began a three-year residency in periodontics and dental implants at Stony Brook University—State University of New York, where he earned his certificate in periodontics. He is an active instructor in professional continuing education on topics including periodontal medicine, computer-guided and minimally invasive dental implant surgery, and periodontal plastic surgery. Dr. Nejat is currently involved in numerous clinical research projects involving flapless dental implant surgery, minimally invasive periodontal plastic surgeries, and computer-guided dental implant surgery with immediate function. Dr. Nejat is a Diplomate of the American Board of Periodontology. He maintains private practices in Manhattan, New York, and Nutley, New Jersey.
Daniel Nejat, DMD
Dr. Daniel Nejat graduated magna cum laude from Drew University with a Bachelor of Arts. He continued his education by receiving a Doctorate in Dental Medicine at the University of Medicine and Dentistry of New Jersey Dental School. Presently, Dr. Nejat is completing his postdoctoral periodontal residency at the New York University College of Dentistry.
Morris Nejat, MD
Dr. Morris Nejat graduated cum laude from Drew University in New Jersey and obtained his medical degree from the University of Medicine and Dentistry of New Jersey, New Jersey Medical School. His internship and residency in pediatrics were completed at North Shore University Hospital, Cornell University Medical College. His allergy/immunology fellowship was performed at the R.A. Cooke Institute of Allergy at St. Luke’s/Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons. Dr. Nejat is Board Certified in pediatrics and has received appointments in pediatrics at St. Luke’s/Roosevelt Hospital Center and Bellevue Hospital Center in New York City.
Dr. Nejat is frequently quoted in the media, including NBC news, Fox News, WB11 News, ABC news, and numerous consumer publications. He also frequently lectures to physicians and consumers on the topics of allergy, asthma, eczema, and food allergies.