Risk factors for Periodontal Disease – A Review

INTRODUCTION

Periodontal Disease is a multi-factorial disease with microbial plaque as the principal initiator of periodontal disease.¹ However, the manifestation and progression of periodontal disease is influenced by a variety of determinants and factors, including subject characteristics, social and behavioural factors, systemic factors, genetic factors, local factors and other emerging risk factors. With large array of factors that influence the development and progression of periodontal disease, understanding what the relationships of these various factors and determinants are to the initiation and progression of periodontal disease can be daunting.²

In assessing risk for disease, periodontal disease can be thought to be more like some of our common medical conditions. Certain people are at higher risk than others and efforts at prevention and intervention involve a combination of personal behaviors and professional practices. Risk assessment efforts applied to periodontitis have only recently received attention, primarily because of the prior paradigm regarding the etiology and progression of the disease involved a ubiquitous condition, gingivitis inevitably leading to periodontitis. Under this paradigm, the prevalence of the condition was extremely high and little error in prediction resulted when everyone was categorized as having the disease.³

As our concepts of periodontal diseases evolved, we realized that the prevalence and incidence rates for periodontitis are much lower than were estimated previously and that some people are more likely to be affected with the condition than others.

It is no longer appropriate to consider all people to be at the same level of risk for periodontitis. Thus, the identification of risk factors serves two important purposes. Risk factor should be able to be used to more accurately identify who is at risk for the condition and they can provide clues to appropriate avenues of intervention.

The aim of this review paper is to explain some basic concepts related to understanding periodontal risk factors and the strength of the association of those risk factors to the initiation and progression of periodontal disease and to present a brief overview of risk factors for periodontal disease.

RISK

It is the probability that an individual will develop a specific disease in a given period of time. The risk for developing disease will vary from individual to individual.

Risk Factor

An environmental, behavioural or biologic factor confirmed by temporal sequence usually in longitudinal studies, which if present directly increases probability of disease.

RISK FACTORS FOR PERIODONTAL DISEASE CAN BE BROADLY CLASSIFIED As⁴

1.E N V I RON M E N TA L , A CQU I R E D A N D BEHAVIORAL FACTORS

• Microbial risk factors
  • Aggregatibacter actinomycetemcomitans
  • Bacteroides forsythus
  • Porphyromonas gingivalis
  • Smoking
  • abetes mellitus
  • Obesity
  • Osteopenia/osteoporosis
  • Human immunodeficiency (HIV) infection
  • Psychosocial factors.

2.Non-modifiable background factors

• Age
• Gender
• Genetic polymorphism
• Race/ ethnicity.

ON THE BASIS OF MODIFYING FACTORS INVOLVED IN PERIODONTAL DISEASES RISK FACTORS FOR PERIODONTAL DISEASE CAN BE CLASSIFIED AS

1.External modifying factors

• Smoking
• Socio economic status
• Human immunodeficiency (HIV) infection
• Psychosocial factors
• Effect of drugs

2.Internal modifying factors

• Genetic polymorphism
• Diabetes mellitus
• Aging
• Puberty, pregnancy and menopause
• osteoporosis
• Neutrophil defects

3.Local Factors

• Cervical enamel projections
• Enamel pearls
• Palato-gingival groove
• Root proximity
• Tooth Restorations
• Open contacts
• Tooth Position

RISK FACTORS FOR PERIODONTAL DISEASE CAN ALSO CLASSIFIED AS

4.Risk factors

• Microbial risk factors
• Smoking
• Diabetes mellitus
• Neutrophil defects

5.Risk indicators

• Age
• Osteoporosis
• Drugs
• Tooth Related Factors

6.Risk Marker

• Nutrition
• Obesity
• Alcohol
• Psychological Factors
• Human immunodeficiency (HIV) infection

7.Risk Determinants

• Genetic Factors
• Race/Ethnicity
• Gender

MICROORGANISMS AS RISK FACTORS

In the mid 1900's, periodontal disease was believed to result from an accumulation of plaque in conjunction with diminished host response and increased host susceptibility with age. However, several observations contradicted these conclusions. First, some individuals with considerable amount of plaque and calculus, as well as gingivitis, never developed destructive periodontitis. Furthermore, individuals showed site specificity in the pattern of disease. In the presence of a uniform host response, these findings were inconsistent with the concept that all plaque is pathogenic.

However, in the case of periodontitis, three primary problems are the inability to culture an organism that has been associated with disease (e.g. many of the oral spirochetes), the difficulties and the lack of a good animal model system for the study of periodontitis.⁵ At the 1996 World Workshop on Clinical Periodontics, a group reviewing specific periodontal pathogens as causative agents in periodontal disease limited their findings to three organisms: Aggregatibacter actinomycetemcomitans, Bacteroides forsythus and Porphyromonas gingivalis, presumably because they met Socransky's modifications of Koch's postulates.⁶

These organisms interact with the hosts by the production of several virulence factors as well with their ability to invade the connective tissue.

SMOKING AS RISK FACTOR

Smoking is related to the development of periodontal disease in a dose related fashion. Nicotine in the cigarette adversely affects the proliferation, the attachment and the chemo taxis of periodontal ligament cells. Cotinine from smoking was reported to enhance the effects of toxins from periodontal pathogens in a chick embryo toxin assay, suggesting a mechanism by which smoking contributes to the severity of periodontal disease.⁷

In studies done by Bergstrom J, Preber H in 1985 & 1986 showed that smokers had less bleeding sites when compared to non-smokers. Both these studies lend support to the fact that smoking depresses the gingival inflammatory response.⁸

Haffajee & Socransky studied 289 adults with periodontitis and concluded that smokers have the greatest attachment loss, deeper periodontal pockets and more missing teeth, fewer sites with gingival bleeding on probing, similar dental plaque levels and gingival inflammation than those who had never smoked.⁹

Surgical therapy also seems to have a less favourable response from smoker patients. In a longitudinal comparative study by Ramjford (1982 ) studied the effects of four different treatment modalities including coronal scaling, root planning, modified Widman flap surgery and osseous resective surgeries smokers consistently showed less pocket reduction and less gain in clinical attachment levels than non-smokers and past smokers.

DIABETES AS RISK FACTOR

An alteration in the host immune inflammatory response may have a major influence on the increased prevalence and severity of periodontal destruction in diabetics, since most of the culture studies show that the bacterial microflora at periodontally diseased sites in diabetic subjects is similar to the microflora at similarly diseased sites in non-diabetic subjects.¹⁰

In a study of the Pima Indians, the incidence and prevalence of periodontal disease were determined in 2,273 subjects. The prevalence of periodontitis was 60% in subjects with diabetes and 36% in non-diabetics.¹¹

The function of immune cells, including neutrophils, monocytes and macrophages, is altered in diabetes. Neutrophil adherence, chemotaxis and phagocytosis are often impaired, which may inhibit bacterial killing in the periodontal pocket and significantly increase periodontal destruction. Although the function of neutrophils is often diminished in diabetics, the monocytes/macrophage cell line may exhibit up regulation in response to bacterial antigens. The hyper responsive monocytes/macrophage results in significantly increased production of pro-inflammatory cytokines and mediators.¹²

On the other hand inhibition of osteoblastic cell proliferation and collagen production results in reduced bone formation and reduced mechanical properties. In individuals with sustained hyperglycemia, proteins become irreversibly glycated to form advanced glycation end products (AGEs). These stable carbohydrate-containing proteins have multiple effects on cell-to-cell and cell-to-matrix interactions and are commonly thought to be a major link between the various diabetic complications. The formation of AGEs also occurs in the periodontium and higher levels of periodontal AGE accumulation are found in those with diabetes than in non diabetic subjects.¹²

AGEs activate a receptor known as “receptor for AGEs” (RAGE) found on the surface of smooth muscle cells, endothelial cells, neurons, monocytes/ macrophages. This receptor is found in the periodontium and a 50% increase in mRNA for RAGE was identified in the gingival tissues of type 2 diabetic subjects compared to non-diabetic controls. AGERAGE interaction on the endothelium results in increased vascular permeability and thrombus formation. These AGERAGE interactions alters the phenotype of the monocytes/macrophages and results in increased production of pro-inflammatory cytokines such as interleukins (IL-1β) and tumour necrosis factor (TNF-α).¹²

Both qualitative and quantitative defects in neutrophils results in varying degree of susceptibility to infection. These qualitative and quantitative defects may be inherited, acquired or drug induced. Qualitative disorders of neutrophils corresponds with the major neutrophil processes; margination (rolling and adhesion), chemotaxis, phagocytosis, degranulation and killing.¹³

Defects in margination can occur at 2 levels. The first is the defect in Sialy Lewis X protein (CD-15s), defect in this glycoprotein will result in the loss of the neutrophils ability to roll along the endothelial lining of venules. Alterations in the selectin mediated rolling function prevent the neutrophils egress from the venules. The disease associated with this defect is leukocyte adhesion type 2.

The second neutrophil defect involving margination is at the level of neutrophil adhesion to the endothelial cell. Defect in the neutrophil surface integrins CD18/CD HA, CD18/CD11b and CD18/CD HC prevent the neutrophil from adhering to the endothelium, ability of neutrophils to adhere to endothelial cells prevent the migration of neutrophils to the site of infection.¹⁴

Defects in neutrophil chemotaxis can be either inherited or secondary to a number of other neutrophil defects caused by diseases or medications. Any alteration in the neutrophil cytoskeleton or its ability to sense or respond to chemotactic gradient will interfere with cells ability to reach site of infection.

Primary defects in neutrophil phagocytosis are rare. Impairment of phagocytic function is usually caused by deficiencies in certain immunoglobulin isotypes and other opsonization factors than intrinsic defects in neutrophil.

Defects in intracellular killing can be divided into those disorders affecting the oxidative or non-oxidative pathway. Degranulation within neutrophil is a non –oxidative pathway.

There are 2 main conditions with defects in degranulation.

• Chediak Higashi syndrome.
• Specific granule deficiency.

The neutrophils oxidative killing mechanism involves 2 main enzymes that, in rare instance, can be dysfunctional.

The first involves defect in 5 components of complex enzymes NADPH oxidase, which catalyzes the respiratory burst with the production of microbicidal superoxide anion, hydrogen peroxide and hydroxyl radical. Without this oxidative reaction, bacterial killing is greatly impaired. This neutrophilic defect is responsible for life threatening recurrent infections found in chronic granulomatous disease.

Another defect in the oxidative pathway is the absence of myloperoxidase. A defect of this enzyme will leads to lack of  hypochlorous acid and a delay in bacterial killing.¹⁵

RISK INDICATORS

Age

Age, for a long time was considered as an important risk factor for attachment loss, however, recent studies have shown otherwise. Like other tissues, the connective tissue of the gingiva cannot avoid the aging process. With increasing age, the fibre and cellular contents decrease and the structure of the ligament becomes more and more irregular. Apart from the decrease in cell density, results of several studies reveal that the mitotic activity of the cells decreases with age.¹⁶

Another possible explanation is that aging fibroblasts synthesize a different type of collagen. Mayne et al¹⁶ have described such a phenomenon for aging chondrocytes. Even the host response to bacterial plaque changes with age. The conditions in the oral cavity are undergoing constant change with age, which may influence the attachment, growth and metabolism of the microorganisms.

However, the current plaque-driven diagnostic classification of periodontal diseases remains mostly supported by a biological assumption, largely modelled on experimental gingivitis and not by epidemiologic studies that controlled for essential factors such as smoking, diabetes, socioeconomic status and even age. So age cannot directly influence the periodontal disease but acts as a background factor, hence being termed as a risk indicator.

Osteoporosis

Osteoporosis and osteopenia are systemic disorders characterized by low bone mass and micro architectural deterioration with a consequent increase in bone fragility and susceptibility to fracture.

Jeffcoat MK et al¹⁷ , analysed alveolar bone heights and density changes in osteoporotic women and women with normal bone mineral density (BMD) scores. The subjects were postmenopausal women enrolled in periodontal maintenance program. Osteoporotic women exhibited a higher frequency of alveolar bone height loss and crestal and sub crestal bone density loss relative to women with normal BMD. The authors concluded that osteoporosis is a risk factor for alveolar bone density loss in postmenopausal women with a history of periodontitis.

Medications

The effects of medications on periodontal health have been grouped into six categories.

A) Behavioural alteration of oral hygiene methods

B) Alteration of Plaque composition

C) Effects on gingival tissue

D) Effects on alveolar bone

E)Effects on gingival crevicular fluid and

F)Effects on salivary flow

Behavioural Alteration: Patients, who take certain medications, have a depressant effect on CNS. These patients may not give importance to their oral hygiene and may have a tendency towards increased plaque accumulation. The drugs that have such an effect include sedatives, tranquillizers and narcotic analgesics.

Alteration of Plaque Composition: Plaque composition and pH may be altered significantly by the dosage of drug administration. Liquid or chewable pharmaceutical preparations for children are made palatable by the addition of sucrose, glucose, or fructose as sweeteners this might cause alteration in pH of plaque and its composition. Sugar metabolized by bacteria to acid end products lowers pH of plaque. The lowered pH near the tooth surface causes ionic dissolution of the hydroxyapatite crystal. This increases roughness and enhance the ability for plaque to be more adherent. It has been shown that human plaque pH decreased significantly after administration of liquid iron supplements and cough syrups.

Effects on gingival tissue: Phenytoin was the first drug reported to produce gingival enlargement. The incidence of gingival enlargement due to the drug ranges between 3% and 62% with a mean 50%. Gingival enlargement has also been associated with a number of calcium channel blockers including nifedipine, verapamil, diltiazem and oxodipine. Gingival enlargement is seen in approximately 5% of patients these medications. Gingival enlargement has also been reported with cyclosporine with an incidence of approximately 25%. It is also postulated that cyclosporine alters fibroblastic activity through effects on a variety of cytokines such as interleukins.^18,19

Effects on salivary flow: Adequate salivary flow is critical to the maintenance of health of oral soft tissue. It has been suggested that mouth breathers have modified plaque accumulation and associated with soft tissue changes. In addition to the effects of xerostomia on soft tissues, root surface caries may be more prevalent.

Tooth Related Factors: Several conditions exist around teeth that may predispose the periodontium to disease. These situations may occur as a result of the condition or position of teeth or as a result of tooth treatment. For instance, some studies have shown association between enamel projections and furcation involvement among molars. Similarly enamel pearls have been implicated in molar furcation involvement.²⁰ It has been hypothesized that the enamel projections prevent the attachment of connective tissue, thus making the area more susceptible to periodontal breakdown.

Tooth position can also present as a risk for periodontal disease. Malalignment, crowding and migration or tipping of a tooth in an edentulous area have all been implicated in loss of periodontal support. In addition extreme labial or lingual tipping of the tooth has been correlated to recession in that area.²¹

Open contacts have been shown to be associated with increased probing depths and loss of clinical attachment. In addition to that root abnormalities, in particular palatogingival grooves in maxillary incisors have been found to be associated with loss of clinical attachment and bone loss.²²

Tooth restorations can also act as risk factors for periodontal breakdown. This can be the result of marginal discrepancies or fixed orthodontic appliances. Amalgam overhangs have been liked to significant bone loss. Subgingival crown margins as opposed to supragingival margins have been implicated in greater gingival recession and increased inflammation.²³

RISK MARKERS

Nutrition: The potential mediating role of nutrition in the oral health-systemic disease relationship has increased interest in the effect of nutrition in oral health and periodontal disease. Deficiency of various vitamins (A, D, E, K, B and C), proteins and lipids have shown adverse effects on periodontal health.

Vitamin A is involved in the production and maintenance of epithelial cells of the skin and mucus membranes and a deficiency may produce dermatologic, mucosal and ocular changes. De Menenzes et al²⁴ reported gingival erosions, ulcerations, bleeding, loss of keratinization and colour changes in vitamin A hypervitaminosis.

Vitamin B complex does not have any particular oral changes but their deficiency can cause oral changes such as glossitis, angular cheilitis, atrophy of lingual papillae and oral ulcerations. ²⁵

Vitamin C is a water soluble vitamin, which is important in the hydroxylation of proline and lysine in collagen. Collagen is a primary connective tissue fibre in the gingival tissue and major constituent of supporting alveolar bone.²⁶

Gender: Periodontal disease is seen more in males in population studies than females at comparable ages. This was seen in several studies done by Genco et al^36,37. Males usually exhibit poorer oral hygiene than females. However, when correcting for oral hygiene, socio economic status and age, male gender is associated with more severe periodontal disease when either attachment loss or bone height is used as the dependent variable. The reasons for these gender differences are not clear and their elucidation may reveal important destructive or protective mechanisms.^36,37

Race: The role of race as a risk factor for periodontal disease is a more complicated issue. Studies done by Beck et al³⁸, showed that approximately three times more blacks had advanced periodontitis as compared to whites of the same age cohort. In an analysis of risk indicators for black and whites, there were more indicators relating to the socio economic status for blacks than whites. They also found that Prevotella intermedia is a risk indicator for blacks but not for whites. Hence, their analysis and studies done by others addressing the issue of race found that when blacks and whites were matched for their socio economic status, the differences often disappeared.³⁸

CONCLUSION

The above review clearly shows that periodontal disease is a multi-factorial disorder. Apart from microbial plaque being principal etiologic factor, several other local and systemic factors have important modifying roles in its pathogenesis of periodontal disease. Of the numerous behavioural and environmental risk factors identified above, only few may be true risk factors possessing a causal relationship with initiation and/or progression of attachment loss.

Effective disease management should include an identification of risk factors for periodontal disease and assessment of disease risk due to these factors.

With further longitudinal studies evaluating all reported risk factors for periodontal disease progression, it is hoped that we can one day use these risk factors to more accurately predict disease progression as well as long term outlook for treated teeth.