Periodontal Diseases and Systemic Health

Periodontal diseases are a group of conditions that affect the gums (gingiva) and destroy the underlying supporting tissues——the alveolar bone, cementum, and periodontal ligament. Periodontal diseases are broadly classified into gingivitis and periodontitis. Defined as inflammation of the gingiva, gingivitis is common in adults as well as children. Periodontitis occurs when the inflammatory infiltrate spreads from the gingiva into the underlying supporting tissues, resulting in periodontal pockets and alveolar bone loss. Bleeding when a periodontal instrument is placed into the pocket indicates inflammation. Tooth looseness can occur later in the disease process. Periodontitis usually affects adults but can occur in severe forms in children.

Periodontal diseases are infections caused by bacteria found in dental plaque. Dental plaque is a complex mass comprising bacteria and their metabolic byproducts, toxins, viruses, food debris, and dead cells. Bacteria in dental plaque adhere to teeth above (supragingival) and below (subgingival) the gumline and other oral surfaces. Some bacteria can invade the soft tissues, eluding removal by instrumentation. Once dental plaque organizes on the tooth surface near the gingiva, a series of inflammatory and immunological responses to the plaque occur. The net result is periodontal breakdown.

Pathogenesis
Of the over 350 bacterial species living in the mouth, about 20 have been identified to be associated with periodontal diseases.¹ From the oral cavity, microorganisms or their products may gain direct entry to the deeper tissues—either by spreading along fascial planes, through bony cavities, or along blood or lymph vessels or nerves.² Thus, bacterial pathogens found in the mouth of a susceptible individual with periodontaldisease may become involved in causing a systemic disease.

Calculus, or tartar, is a secondary or contributing etiologic factor in causing periodontal diseases. Calculus is calcified dental plaque; it does not contain living microorganisms, as does dental plaque; however, its surface is porous, allowing the accumulation of plaque.

Because the prevalence and severity of periodontal diseases have changed over the years, individuals are not considered to be equally prone to periodontal diseases. Thus, some individuals are more “at risk" for developing periodontal diseases than others. Certain factors put individuals at risk for developing periodontal diseases. On the other hand, a more recent concern is that if a patient has periodontal disease, he or she may be at risk for other medical conditions. This article will review risk factors for developing periodontal diseases as well as discuss the medical conditions that can develop if the patient has pre-existing periodontal disease.

Risk Assessment
A risk factor is an aspect of personal behavior or lifestyle or an environmental exposure that, if present, is strongly associated with causing the disease.³ A risk indicator is a potential risk factor which needs further clinical studies to be confirmed as a true risk factor.⁴ A risk marker/predictor is a factor that, if present, indicates an increased probability of disease but is not a causative agent.⁴ Risk markers have not been confirmed by longitudinal studies. Risk factors for periodontal diseases are reviewed in TABLE 1. Medical conditions associated with the development of periodontal diseases are reviewed in TABLE 2.

Risk Factors
Bacteria: Pathogenic bacteria are bacteria that produce disease. Certain bacteria—such as Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus actinomycetemocomitans, Eikenella corrodons, and Bacteroides forsythus—are implicated in periodontal diseases. The presence of pathogenic bacteria alone does not necessarily indicate the patient will develop periodontal disease. The environment of the pocket area and the health and immune status of the patient also play a role in the development of periodontal disease.

Smoking: Another risk factor is cigarette smoking. Smoking may not only be associated with the development of periodontal diseases but it may affect the successful outcome of periodontal treatment. Smoking is associated with increased failure rates of dental implants.^5,6 Some studies have found that former smokers have a greater probability for periodontal diseases compared to those who have never smoked.^4,7

On the contrary, some studies reported that ceasing smoking may restore the normal periodontal healing response⁸ and may retard progression of alveolar bone loss.⁹ Most clinical studies have found that smokers have greater amount of plaque and calculus accumulation, greater pocket depths, and bone loss.¹⁰ Tobacco smoke can have deleterious effects on various polymorphonuclear leukocytes?(PMNs) functions,¹¹ resulting in an impaired immune system. Prolonged exposure of tobacco smoke can lead to irritations on the oral mucosa, consisting of whitish keratotic patches, or hard, fibrotic gingiva.

It is well established that smokeless tobacco products such as snuff and chewing tobacco can cause oral carcinoma.¹² The relationship of smokeless tobacco to periodontal disease is less clear.¹⁰ Some studies have found increased incidence of gingival recession in areas adjacent to the site of tobacco placement¹³ in patients with pre-existing gingivitis.

Patients should be counseled on smoking cessation. Patients need to understand that besides being a risk for oral cancer, smoking is also an established risk for periodontal diseases and it impairs periodontal healing (e.g., soft tissue healing after scaling and root planing or periodontal surgery).

Diabetes Mellitus: Diabetes mellitus is a risk factor for periodontal diseases.¹⁴ It is well established that patients with diabetes mellitus, especially if the disease is poorly controlled or uncontrolled, are more prone to periodontal destruction. For well-controlled diabetics, periodontal disease responds well to therapy and can be managed successfully.

Many pathophysiological changes occur in diabetes. Microvascular changes occur in the gingiva similar to those in other organs. There is thickening of the basement membranes and narrowing of the lumen,¹⁵ which result in impaired oxygen and nutrient delivery to the tissues. Impaired neutrophil function may be responsible for the severe periodontal destruction in diabetics.¹⁶ The PMNs do not function properly in eliminating invasive, pathogenic bacteria.

Collagen is a protein found in all connective tissues of the body, including the periodontium (gingiva, alveolar bone, periodontal ligament, cementum). Normal collagen turnover occurs with new collagen production replacing the “old?collagen. This is necessary for maintaining periodontal health. In diabetics there is an altered collagen metabolism with an upset in this equilibrium. Increased collagen breakdown contributes to periodontal destruction.

Risk Indicators
Osteoporosis: There may be an association between osteoporosis and alveolar bone loss around a tooth.¹⁷ Women with osteoporosis have reductions in bone mineral content (bone mass), which increases the risk for fracture. Since the loss of alveolar bone around the tooth is a result of periodontal diseases, osteoporosis has been suspected to be related to periodontal diseases.¹⁸ However, further studies are needed in order to confirm this relationship.

HIV/AIDS: Human immunodeficiency virus (HIV) is considered a risk indicator for periodontal diseases. Any disease with a compromised host-immune system predisposes patients to periodontal diseases. Not only are there oral lesions but a severe gingivitis (linear gingival erythema) and periodontitis (necrotizing ulcerative periodontitis) are associated with this infection.¹⁹

Medications: Adverse side effects of certain medications may present with dental concerns. One side effect is enlargement or overgrowth of the gingiva. Histologically, the overgrowth is primarily due to an excessive production of collagen by fibroblasts in the connective tissue of the gingiva (connective tissue is underneath the epithelium, which is the outer surface of the gingiva). Clinically, the gingiva appears thickened and enlarged.²⁰ Enlargement often occurs 1? months after the start of the medication.²¹ The relationship between dosage and severity may not be causal; however, the level of plaque accumulation does determine the extent of overgrowth.

Drug-induced gingival overgrowth has been reported with phenytoin (in about 50% of patients),²² cyclosporine (in about 25% of patients),²³ and calcium channel blockers (prevalence varies up to 30%).²⁴ Although nifedipine is most frequently associated with gingival enlargement, overgrowth can occur with any drug in this class (Figure 1).²⁴

Meticulous oral hygiene is necessary to prevent and treat gingival overgrowth. Due to the excessive amounts of tissue growth, it is difficult to perform optimal oral hygiene. The enlarged tissue can interfere with occlusion, chewing or speech. When the gingiva is removed surgically, enlargement often recurs. However, when the drug is discontinued it disappears. The patient’s physician should be informed regarding the patient’s oral condition and consider if an alternative drug could be prescribed.

Saliva plays an important role in the defense mechanism of the soft and hard tissues in the mouth and in such functions as taste, mastication (chewing) and deglutition (swallowing). Besides aging, radiation therapy, surgery involving the salivary glands, and conditions such as Sj?ren’s syndrome, certain medications may cause xerostomia (dry mouth) by significantly decreasing salivary flow. Xerostomia commonly results in opportunistic bacterial and yeast infections, increased dental decay, and difficulty in speaking and in maintaining normal dietary intake.²⁵ Additionally, there is an increased incidence of periodontal diseases due to enhanced dental plaque accumulation. Examples of some medications that cause dry mouth are listed in Table 3. The prevalence of xerostomia may be correlated with the total number of such drugs taken per day.²⁶

Most side effects occur because the drug is not selective in its action. Antidepressants work by binding to certain receptors, thus blocking the reuptake of neurotransmitters. If a drug blocks the muscarinic receptors, anticholinergic side effects such as dry mouth, constipation, urinary retention, blurred vision and tachycardia may result. If a drug blocks the histamine H₁ receptors, side effects such as sedation, weight gain and hypotension may occur. Gastrointestinal side effects (e.g., nausea, diarrhea), sexual dysfunction, insomnia and anxiety are associated with serotonin reuptake blockade.

Link to Systemic Diseases
Due to the chronic nature of periodontal diseases, which are infections, and involvement of the host’s immune system, it seems reasonable to hypothesize that these infections may affect the overall health of an individual.²⁷ It is only within the past year that this aspect of periodontal diseases has been recognized and studied. Periodontal diseases may, in fact, be a risk factor for a number of systemic diseases (Table 2).

Cardiovascular Disease: Cardiovascular disease (CVD) is one of the most common medical conditions in patients with periodontitis.^28,29 Patients with periodontitis have been documented to have a one-and-a-half to two times increased risk of coronary heart disease and are three times more likely to suffer a stroke than are those with minimal periodontal disease.³⁰ Also, there was a greater incidence of CVD in men under 50 years of age with periodontal diseases³¹ than those over 50.³² There was a one-and-a-half to two-fold greater risk of having a fatal heart attack in patients with periodontal disease than in patients without a periodontal infection.³³

Several theories have been proposed for these data, including the effect of bacteria on the cells involved in atherosclerosis.²⁹ Oral bacteria such as Porphyromonas gingivalis induce aggregation of platelets through the binding of a specific surface protein.33 Periodontal disease may soon be included in the list of risk factors for CVD, along with smoking, hypertension and high cholesterol.

Respiratory Disease: The course of bacterial pneumonia involves the aspiration of bacteria in the oral cavity, specifically the oropharyngeal area, into the lower respiratory tract. Pulmonary infection results when the host’s immune system cannot get rid of the colonizing bacteria. Certain Gram-negative bacteria found in pneumonia patients have also been cultivated in periodontal pockets.³⁴ Pneumonia is more prone to occur in hospitalized patients, alcoholics, smokers, the elderly, or patients with other health problems that suppress the immune system. These patients may have poor oral hygiene, and often harbor respiratory pathogens in their dental plaque.³⁵

Chronic obstructive pulmonary disease (COPD) occurs when there is an obstruction of airflow due to bronchitis or emphysema. One study found that patients with periodontitis characterized by alveolar bone loss had an increased risk for COPD.³⁶

Premature Birth: Periodontal infections may be a risk factor for pre-term low-birth-weight (PLBW) babies.³⁷ Considering periodontal diseases are, for the most part, preventable and treatable, the literature supports the importance of addressing periodontal problems promptly in women of childbearing age.³⁸ Mothers with periodontal disease have about an 8-fold greater chance of having PLBW babies than do mothers without periodontal diseases.³⁹ A proposed mechanism suggests a concentration-dependent relationship between increased maternal levels of prostaglandin E₂ in the gingival fluid found in the pocket and PLBW.⁴⁰ More research is needed to confirm how periodontal diseases may affect pregnancy outcomes. If it can be definitely determined that periodontal disease is a risk factor for PLBW babies, this may help to reduce the mortality associated with premature birth.

Diabetes Mellitus: Patients with diabetes mellitus (DM) are more at risk for periodontal diseases than are individuals without diabetes. Recent studies suggest that the relationship between periodontal diseases and DM goes both ways; periodontal disease may make it more difficult for people with diabetes to control their blood sugar. This puts the diabetic at increased risk for diabetic complications. Controlling periodontal disease may help patients control their diabetes.

Conclusion
Occasionally, patients presenting with periodontal diseases may not show the characteristic clinical and radiographic appearance of the lesions and do not reflect the known etiologic factors. Since the oral cavity represents an ecosystem which has to continually cope with the bacterial challenge, it may also reflect impaired host responses or systemic conditions of the patients at an early stage of the disease process. For instance, the development of an HIV infection or diabetes may be recognized in the periodontal tissues before the diseases are realized by the patient.

Current research has indicated a link between periodontal diseases and systemic conditions. It is a double-edged sword: smoking, diabetes and pathogenic bacteria are established risk factors for periodontal diseases, whereas periodontal diseases may put individuals at increased risk for health problems such as heart disease, diabetes, respiratory diseases and pre-term low-birth-weight babies. Genetics does play a role in the development of periodontal diseases but it is not an established risk factor. Not all people respond the same way to dental plaque. Some individuals may genetically be at increased risk for periodontal diseases.⁴¹

Heart disease, diabetes, respiratory diseases and pre-term low-birth-weight babies are concerns for all health professionals. The pharmacist needs to counsel individuals on the importance of controlling their disease state (cardiovascular, diabetes, respiratory). It is evident that pharmacists, physicians and dentists should improve their collaboration for the benefit of improving patient care. This new concept of periodontal medicine influences the examination procedures, diagnosis, and the treatment of oral problems. Periodontal diseases and the overall health of the patient may change the manner in which pharmacists, physicians and dentists are educated and interact.