It's more than the mouth: the effects of periodontal disease on systemic health.

Periodontal disease is estimated to affect 75% of the people in the United States to some extent, and 20 to 30% of the country's adults suffer moderate to severe forms of the disease. (1) Prevalence and severity of destructive periodontal disease increase with age, and it is most prevalent in the African-American and Hispanic-American populations. (2) Although epidemiological studies indicate that gingival health in America is slowly but steadily improving, severe periodontitis afflicts approximately 14% of adults aged 45 to 54 and 23% of adults aged 65 to 74. (3)

Dental professionals have long suspected associations between periodontal disease and a variety of systemic conditions. During the past few decades, researchers have attempted to establish links between periodontal infections and cardiovascular disease, respiratory infections, osteoporosis, diabetes and preterm births. Though the nature of the relationship is not fully understood, research efforts clearly point to a connection between periodontal and systemic health. Some of the most convincing evidence associates periodontal disease with diabetes, cardiovascular disease, and delivery of preterm, low birth weight babies. In order to understand these connections, it is necessary to be familiar with the periodontal disease process.

Progression of Periodontal Disease

Although periodontal disease can be defined as any disorder that affects the surrounding and supporting tissues of the teeth, the term usually refers to the two most common plaque-induced forms of the disease, gingivitis and periodontitis.

Gingivitis, the mildest form of periodontal disease, involves the soft tissue structures surrounding the teeth, and is characterized by redness, swelling and bleeding of the gingiva. Found only in the epithelium and connective tissues, this is one of the most common human diseases. (4) It is caused by the bacterial plaque, or biofilm, which forms on the teeth and underneath the gums. Mild gingivitis is easily reversible with daily removal of the irritating biofilm; however, if plaque is allowed to remain and collect for extended periods, inflammation can extend deeper into the tissues, resulting in periodontitis.

Periodontitis involves the supporting structures of the teeth. It is cyclic in nature, with periods of intense activity followed by extended periods of inactivity. Chronic periodontitis progresses slowly, and often goes undetected during the early stages. Tissue destruction during active periods leads to loss of connective tissue attachment at the base of the gingival sulcus, resulting in the formation of soft tissue pockets.

Once a periodontal pocket forms, removal of the biofilm by the patient becomes more difficult, and the area provides a harbor for bacteria. Without adequate professional treatment, inflammation extends into the alveolar bone that supports the teeth, and destruction of this bone can lead to tooth mobility and eventual tooth loss. Periodontal disease is the leading cause of tooth loss in adults. (4)

Cause

Over 400 different species of bacteria can be found in the biofilm infections that are responsible for the initiation of periodontal disease and certain clusters of these species, including Porphyromonas gingivalis, Tannerella forsythenis and Treponema denticola that are commonly associated with the disease.(5) As plaque matures, gram-negative, anaerobic bacteria increase in number. These bacteria, which are generally more virulent, can invade soft tissues and release toxic products that trigger the tissue inflammation seen in gingivitis and periodontitis.

Release of bacterial toxins and resulting inflammation stimulates a response from the body's immune system. Neutrophils, the first line of defense in the immune response, are summoned to the inflamed areas, where they are soon joined by other immune cells. Unfortunately, much of the destruction seen in periodontal disease is caused when an exaggerated response by some of the immune cells leads to production of enzymes and cytokines that can destroy connective tissues of the periodontium.

Although bacteria are necessary for periodontal disease to begin, environmental and genetic factors that alter the body's response to oral bacteria help determine the degree and severity of disease. In this country, the risk of developing periodontitis for long-term smokers is equal to the risk of developing lung cancer, (6) and smoking accounts for about half the risk of developing periodontal disease. (7) Periodontal disease often occurs or becomes more severe when an individual's immune system is impaired by systemic problems or disease. In turn, periodontal disease may increase a patient's susceptibility to certain diseases and conditions.

Periodontal Disease and Diabetes Mellitus

Diabetes, which was first recognized as a disease over 2,000 years ago, represents a huge, worldwide health problem. It is estimated to affect approximately 20 million people in the United States, with incidence increasing at the rate of 500,000 cases per year. (8) Diabetes is the seventh leading cause of death in this country, and results in a number of long-term complications, including blindness, kidney failure, heart disease, strokes and nerve damage. (9) Over 90,000 amputations each year are attributed to complications from this disorder. (9)

Diabetes, also called diabetes mellitus, is a chronic disorder caused by the body's inability to produce enough or properly use insulin, leading to high levels of glucose in the blood. It comprises a group of diverse disease forms, including Type 1, Type 2, and gestational diabetes.

Type 1, a genetically determined autoimmune disorder, occurs when the pancreas is incapable of producing insulin. This form, which primarily occurs in children and young adults, is usually treated with insulin injections. Type 2 diabetes develops most often after the age of 45, and accounts for 90 to 95% of all diabetes in the United States. (9) It parallels the increase of obesity, and is nearing epidemic proportions in this country. Type 2 develops when cells become "insulin-resistant," thus requiring more insulin to move glucose from the bloodstream into the cells. Treatment may require oral medications or insulin injections, but can sometimes be controlled through exercise and dietary changes.

DM is characterized by disturbances in the balance of glucose intake and insulin, resulting in too much sugar (hyperglycemia) or too little sugar (hypoglycemia) in the blood. Elevated blood glucose levels affect many parts of the body, including the periodontium. In fact, periodontal disease has been referred to as the "sixth complication of diabetes," along with cardiovascular disease, retinopathy, neuropathy, nephropathy, and reduced healing ability. (10)

Many of the classic diabetic complications are related to functional alterations of the immune cells involved in fighting infections, including neutrophils, macrophages and monocytes. A reduction in neutrophil activity has been demonstrated in patients with DM; however, increased responses are seen in monocytes and macrophages. Unfortunately, hyper-response of these immune cells may lead to increased production of proinflammatory cytokines and elevated levels of lipids, both of which can have negative effects on tissue.

The link between periodontal disease and diabetes has been documented more than any of the periodontal and systemic disease connections. Diabetes mellitus-associated gingivitis is classified as a distinct disease entity in current periodontal disease classification lists. (11) Although many diabetic patients never develop periodontal disease, diabetes mellitus is considered to be a risk factor for both gingivitis and periodontitis. As a result of altered immunoinflammatory responses in the host, DM renders individuals more susceptible to all infections, including those that involve the periodontium. (12)

Dental professionals have long suspected that periodontal disease tends to be more severe in patients with diabetes. Studies supporting this theory also suggest a direct relationship between levels of glycemic control and severity of periodontal disease. (13) Researchers found greater prevalence and severity of gingivitis in patients with Type 1 and Type 2 diabetes when compared to nondiabetic controls with similar plaque levels, and that disease severity increased with decreased glycemic control. (8) Further studies showed improvement in gingival condition with improved glycemic control. (8) In a more recent study, patients with well-controlled diabetes still developed gingivitis more easily than nondiabetic controls. These results implicate the systemic inflammation present in diabetics as an etiological factor for periodontal disease. (14)

Evidence from 68 longitudinal studies suggests that glycemic control levels also affect the development of periodontitis, and progression of associated bone loss. Although the evidence is not complete, some of these studies found increased pocket depths, attachment loss and bone loss among patients with poor glycemic control when compared to patients with controlled diabetes. (8)

The mechanism by which diabetes influences periodontal disease is basically the same as that associated with the other diabetic complications. Since neutrophils are responsible for the first line of defense in the periodontal pocket, reduced capability of these immune cells in the diabetic patient allows bacterial proliferation, leading to inflammation and destruction of periodontal tissue. Meanwhile, long-lived proteins and lipids are produced in response to the hyperactivity of certain other immune cells (monocytes and macrophages). Elevated protein and lipid levels in the blood and tissues may lead to vascular injury and reduced potential for tissue repair.

Increasing amounts of evidence show that the association between diabetes and periodontal disease goes both ways: not only does diabetes affect the tissues of the periodontium, but the periodontal condition may also affect blood sugar levels. (5) In a two-year longitudinal study, patients with Type 2 diabetes and severe periodontitis were compared to patients with Type 2 diabetes and no periodontal disease. Risk of worsening glycemic control was found to be six times greater in those patients with periodontal disease. (15) Results of later intervention studies suggest that glycemic control is improved after periodontal therapy. (15) These results are not surprising, since bacterial or viral infections can cause insulin resistance in cells, leading to the production of more insulin and development of uncontrollable blood glucose levels.

Cardiovascular Disease

Cardiovascular disease, of which heart disease and stroke are primary components, is the leading cause of death in the United States. (16) It accounts for 40% of the deaths among adults in the country, and is predicted to be the most common cause of death worldwide by the year 2020. An estimated 25% of the U.S. population is living with CVD, which is responsible for 6,000,000 hospitalizations each year, and the leading cause of permanent disability among the country's adult population.

The pathological basis for cardiovascular disease is atherosclerosis, or thickening of the arterial walls. Risk factors for this condition include gender and genetic predispositions, hypertension, hyperlipidemia, and smoking. Initiation of atherosclerosis may also occur in response to endothelial injury. Such injury can result from infection and inflammation, both of which are commonly seen in periodontal disease.

Several studies have demonstrated a significant risk increase for cardiovascular events in patients with periodontitis, and some of these studies also showed that risk of developing cardiovascular problems increased with increasing severity of periodontitis. However, these cross-sectional and case-control studies cannot prove causal relationships between the two conditions.

Although studies have pointed to an association between periodontitis and cardiovascular disease, researchers have differing views of how the two are related. Some investigators theorize that periodontal infections increase risks for atherosclerosis, which can precipitate a heart attack or stroke. They contend that the harmful bacteria responsible for periodontal disease are released into the bloodstream during normal activities, such as brushing and chewing. These bacteria can then travel to other parts of the body and release dangerous toxins, resulting in a local inflammatory response that leads to blood clots and atherosclerotic plaques. Periodontal pathogens found in human carotid atheromas, as well as coronary and carotid endothelium, support this theory. (17)

One large independent study showed increased thickness of carotid artery walls in elderly people when pathogenic bacteria were present in the periodontal biofilm. A follow-up study of the same population found that subjects with severe periodontal bone loss were at four times greater risk of plaque buildup in the carotid arteries, thus putting them at greater risk of stroke.

Other researchers contend that the association between periodontitis and cardiovascular disease is not directly related to periodontal bacteria, but to antibody production and inflammatory responses of the host. Patients with severe periodontitis have been estimated to have a total surface area of ulcerated pocket epithelium that is equivalent to the size of the palm of the hand. (18) These ulcerated periodontal pockets provide a portal of entry for bacteria and bacterial byproducts (endotoxins and lipopolysaccharides) into the blood-stream, which can directly affect vessel walls.

In an effort to protect against bacteria and toxic bacterial byproducts in the bloodstream, the liver produces acute phase proteins that are capable of causing indirect tissue damage. Although these substances serve proinflammatory functions, they may also have harmful effects on the body. Periodontitis has been associated with increased blood levels of C-reactive protein and fibrinogen, which can modulate coagulation and atherosclerosis, and are accepted risk factors for stroke and heart attack. (19)

Pregnancy Outcomes

Preterm labor, pre-eclampsia, and other adverse events lead to 400,000 premature births each year. Causes of premature delivery are often unknown, but some of the factors that are known to increase risk are smoking, alcohol consumption, low maternal weight, multiple births, previous preterm delivery, socioeconomic status and access to care.

Preterm birth and low birth weight are the most significant predictors of infant health and survival. The average weight for full term infants ranges from about 5.5 to 8 pounds. Babies delivered before 36 completed weeks of gestation are classified as preterm, and are more likely to have weights below this range. Birth weights less than 2500 grams represent a major health problem. Low birth weight is a major cause of infant mortality, and is associated with greater risk for mental and physical disabilities, including respiratory problems, congenital abnormality, neurodevelopmental problems, and behavioral problems. (20) Preterm and low birth weight infants often require long-term hospitalization.

Physicians are well aware that bacterial infections in expectant mothers can result in adverse pregnancy outcomes. Bacterial vaginosis during pregnancy has consistently been linked with miscarriage and spontaneous preterm birth. Specific causes for these adverse outcomes have not been determined, and treatment intervention has failed to significantly reduce premature deliveries.

Early observational studies at the University of North Carolina indicated that premature delivery and/or low birth weight are more common among women with periodontitis.(21) In further studies, harmful effects were seen in fetuses when hamsters were exposed to the byproducts of periodontitis disease during pregnancy. Although the results of these studies point to an association between birth outcomes and periodontitis, there is no proof of a causal relationship.

Recent studies have also suggested that periodontitis in mothers may be associated with increased risk for miscarriage, pre-eclampsia, low birth weight, and preterm birth. However, results from observational studies have been inconclusive, with only 15 of 22 studies showing associations. One British study found increased risk of miscarriage during the second trimester of pregnancy in mothers with periodontitis, but failed to show any association with low birth weight or preterm birth. Six studies point to periodontitis as a risk factor for low birth weight, and seven for preterm birth. Some of these studies showed that risk for adverse pregnancy outcomes increased with increased severity of periodontitis. There is also evidence that periodontal treatment may significantly reduce preterm/low birth weight rate.

The mechanism by which periodontitis affects pregnancy outcomes is still unclear, but infection appears to be a key factor.(22) As with the systemic diseases discussed previously, periodontal pathogens or inflammatory mediators produced in the periodontal tissues could be responsible. Oral microorganisms have been detected in the amniotic fluid and membranes of women in preterm labor, but there is no evidence showing their responsibility for preterm birth. Elevated C-reactive protein levels have also been blamed for miscarriage, fetal growth restriction, preterm birth, and pre-eclampsia. CRP blood levels, a marker for systemic inflammation, have been found to be 65% higher in pregnant women with periodontitis when compared to healthy women. It is hypothesized that amplified inflammatory response caused by these proteins may trigger early uterine contraction and labor.

Conclusion

Even though there is no causal evidence, research continues to confirm that periodontitis is strongly associated with diabetes, cardiovascular disease and adverse birth outcomes. However, since all of these conditions share many risk factors and pathogenic processes, connections could be related to underlying traits or responses that increase risk for periodontitis as well as a number of other systemic diseases and conditions.

Since periodontal disease is both preventable and curable, confirmation that it is an independent risk factor for other systemic diseases and conditions would be of great public health importance. However, inconsistencies in previous study results continue to cast doubt on the significance of a periodontal/systemic disease connection. These inconsistencies could be due to differences in study design, definitions of periodontal disease, and outcome measures of disease. Larger, more controlled, randomized trials are needed to substantiate these links, and additional intervention studies are necessary to demonstrate the potential systemic benefits of periodontal therapy.

While scientists continue to search for answers, dental professionals should stress the importance of oral hygiene, and strive to make patients aware of possible relationships between periodontal health and other systemic conditions. Having this knowledge could help motivate patients to increase oral home care efforts in hopes of improving overall health.

As a member of the dental team, the assistant is in an excellent position to play an important role in the management of patient health. The dental assistant should be responsible for helping to educate patients about the prevention, course, cause and consequences of periodontal disease. Attempts to teach hygiene techniques and motivate patients toward improved oral home care need to be included at each appointment.

Patients should also be kept informed of relevant research findings and products that might be beneficial in controlling disease and maintaining oral health. Antimicrobial agents, such as Triclosan, have proven to be safe and effective when added to toothpaste along with copolymer and fluoride, for treatment and prevention of plaque-related diseases. (23) One study found significant reductions in bacteria found in saliva samples after using a Triclosan/copolymer dentifrice when compared to patients using a traditional fluoride dentifrice. (24) Most patients are unaware of such findings, and rely on health care providers to recommend products that might offer advantages over their usual health care products. Even if causal connections between periodontal and systemic health are never established, patients have nothing to lose from striving to improve oral hygiene, and could only benefit from better oral health.

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Ethel Campbell, CDA, RDH, MS, is a clinical Associate Professor in the Department of Dental Ecology at the University of North Carolina School of Dentistry. She has been teaching at UNC since 1989, and is currently serving as director for the dental assisting program.