PARODONTALNA MEDICINA – NOVA GRANA U OBLASTI PARODONTOLOGIJE PERIODONTAL MEDICINE – THE EMERGENCE OF A NEW BRANCH IN PERIODONTOLOGY

Uvod: Parodontalna medicina predstavlja novu granu u oblasti parodontologije. Parodontalna medicina je termin koji se koristi za različite namene u različitim delovima sveta. U nekim zemljama, to se odnosi na proučavanje se dinamičnog odnos između parodontalnih oboljenja i sistemskih stanja , kao što su kardiovaskularne i cerebrovaskularne bolesti, prevremeni porođaj i rođenje beba male telesne težine , šećerna bolest , osteoporoza i oboljenja respiratornog trakta. Ovakve studije istražuju periferni uticaj zapaljenja parodonta na sistemsko zdravlje. U drugim zemljama, "parodontalna medicina" je termin koji se koristi za opis parodontalnih gingivalnih manifestacija raznih medicinskih stanja. Ovo uključuje ispitivanje, dijagnostiku i terapijski tretman i kako sanacija oralnog stanja utiče na medicinsko praćenje pacijenata kao deo sveobuhvatnog pristupa u okviru definisanih puteva tretmana i nege. Zaključak: Tekst je sveobuhvatna analiza istraživanja o parodontopatiji i njenoj vezi sa sistemskim stanjima. Parodontalni tretman može biti važan u smislu preventive opšteg zdravlja pacijenta. Parodontolozi ukazuju na realnost i edukaciju javnosti na činjenicu da infekcije u ustima mogu izazvati zdravstvene probleme u drugim delovima tela.


Periodontal disease as a risk factor for the patient's general health
There is a growing body of evidence that periodontal infections could influence the overall health and occurrence of some systemic diseases 1 . Periodontal disease is characterized by inflammation and bacterial infection of the gums surrounding the teeth. The bacteria that are associated with periodontal disease can travel into the bloodstream to other parts of the body,which puts health at risk 2 . People think of gum disease in terms of their teeth, but they do not consider the fact that gum disease is a serious infection that can release bacteria into the bloodstream. At the end, results could mean additional health risks for people whose health is already affected by other diseases or lead to serious complications like heart disease.

The link between gum disease and heart disease (attack and stroke)
Cardiovascular diseases (CVDs), including myocardial infarction and stroke, are the leading causes of death in the world. The classic risk factors -age, hypertension, blood lipids, cigarette smoking, stress, hostility, diabetes, weight, family history, diet, alcohol and physical activity -can only account for 2/3 of the variation in the incidence of CVD cases 3 . Again, unrecognized risk factors may contribute to the pathogenesis of CVD. Recent studies have found that patients with periodontal disease have a 1.5to 2.0-fold greater risk of incurring fatal CVD than patients without periodontal disease. In fact, oral infections seem to increase the risk of coronary artery disease to a degree similar to the classic risk factors 4 . There is still much research to be done to understand the link between periodontal diseases and systemic diseases, such as cardiovascular diseases. The emerging area of periodontal and systemic links is one that could have significant impact on public health 5,6 . The findings may be life-saving for some of the nearly one million people who die annually from heart disease.
Ateroskleroza i parodontopatija su inflamatorna stanja koja su obično hronična i asimptomatske prirode. Aktivacija lokalnih makrofaga u parodoncijumu i intimi arterija igra ulogu u inflamatornom procesu ovih bolesti. Formiranje penastih ćelija makrofaga u intimi karotidnih arterija ključni je korak za početk ateroskleroze . Preduslov za formiranje penastih ćelija je v išak tereta holesterola prvenstveno transportovanih u LDL. Stoga, LDL može biti značajan posrednik između oralne infekcije i arterijske inflamacije 23 . Pokazano je takođe da lipopolisaharidi (LPS) iz oralnog biofilma prodiru u gingivu, a pojava bakterijemije se povećava sa povećanjem težine inflamacije gingive. Stoga, po prvi put u okviru našeg saznanja, visoke koncentracije serumskih nivoa LPS-a ukazuju da su zapravo povezani gum disease include bleeding gums or pus between the teeth. If left untreated, this chronic infection can destroy the bone that supports the teeth and may lead to tooth loss 7 . A large body of research has showed that infection and inflammation caused by periodontal disease significantly increase the risk for coronary heart disease [8][9][10] . Studies propose two hypotheses for this occurrence. One hypothesis is that periodontal pathogens present in gum diseases could enter the bloodstream, invade the blood vessel walls, and ultimately cause atherosclerosis (atherosclerosis is a multistage process set in motion when cells lining the arteries are damaged as a result of high blood pressure, smoking, toxic substances, and other agents). The mouth can be a major source of chronic or permanent release of toxic bacterial components in the bloodstream during normal oral functions 11,12 .
Another hypothesis is based on several studies that have shown that periodontal infection and inflammation can be correlated with increased plasma levels of inflammatory markers 13 , such as C-reactive protein 14 , fibrinogen (this creates blood clots), or several cytokines (hormone proteins) 15 , and lipoproteins 16,17 . It has been shown that patients with severe periodontitis have increased serum levels of CRP, fibrinogen, moderate leukocytosis, as well as increased serum levels of IL-1, and IL-6 when compared with unaffected population. Furthermore, in periodontitis patients, elevated serum CRP is associated with high levels of infection caused by periodontal pathogens, which shows that periodotitis plays a role in the etiologic pathway of systemic inflammatory diseases such as atherosclerosis 18 . Inflammatory markers explain one reason why periodontal disease could be a risk factor for cardiovascular disease 14,[19][20][21][22] .
Both atherosclerosis and periodontitis are inflammatory conditions that are commonly chronic and asymptomatic in nature. Local macrophage activation in periodontium and in arterial intima plays a role in the inflammatory process of both diseases. Formation of macrophage-derived foam cells in the arterial intima is the pivotal step in early atherosclerosis. The prerequisite for foam cell formation is the excess cargo of cholesterol preferentially transported in LDL. Therefore, LDL may be an important mediator between oral infection and arterial inflammation 23 . sa površinom zahvaćenog tkiva u parodontopatiji. U cirkulaciji, LPS sarađuju sa svim klasama lipoproteina i mogu inicirati aterogenezu, kada se transportuju u arterijski zid sa LDL-om 24 .
Lipopolysaccharides (LPS) from the oral biofilm have also been shown to penetrate the gingiva, and the occurrence of bacteriemia increases with increasing the severity of gingival inflammation. Therefore, for the first time to our knowledge, it has been shown that high serum concentrations of LPS are actually associated with the area of affected tissue in periodontitis. In circulation, LPS associates with all lipoprotein classes and it may initiate atherogenesis, when it is transported into the arterial wall with LDL 24 .
The American Academy of Periodontology appeals to people who are at risk for cardiovascular disease or have signs of gum disease to consult a dentist having ehperience in treating periodontal disease 25 .

Diabetes and periodontitis
There is a two-way relationship between periodontal disease and diabetes. Diabetics are more likely to develop infections like periodontal disease, and periodontal disease makes it more difficult for people who have diabetes to control their blood glucose 26 . Furthermore, people with diabetes and periodontal disease are more prone to recurrent periodontal abscesses (areas around teeth that are inflamed, infected and painful). It has been assumed that the association is due to the fact that people with diabetes have a compromised ability to fight infections such as periodontal disease 27 . However, this relation is currently being challenged. It is possible that periodontal disease predisposes to or exacerbates the diabetic condition. A recent survey has shown that the concentration of glycated hemoglobin (a measure of diabetic control) is elevated in people with type 2 diabetes and severe periodontal disease. In another study of people with type 2 diabetes, severe periodontitis was strongly associated with an increased risk of poor glycemic control 28,29 .
In addition, a recent study of mothers of PLBW infants, with otherwise low risk, had significantly more periodontal disease than a similar group of women with normal weight infants at birth. The association observed between generalized periodontitis and induced preterm birth shows the strength, along with the extent of periodontitis [31][32][33] .
There is conflicting research results regarding the relationship between periodontal diseases and adverse pregnancy events. The study authors indicated that the primary theory to explain the relationship between perio-dontitis and pre-eclampsia is that inflamed periodontal tissues release elevated levels of C-reactive protein (CRP), prostaglandin E2 (PgE2), and other inflammatory mediators into the general circulation, inducing damage to the placenta, resulting in pre-eclampsia. Regardless of the mechanism triggering PLBW, the chronic inflammation associated with periodontal disease seems to increase the risk of PLBW.
Three hypotheses that may explain the relationship between periodontal infection and PLBW are as follows: 1) periodontal pathogens cause direct contamination in the fetoplacental unit 34 , 2) lipopolysaccharide, a bacterial endotoxin normally found in infected periodontal tissue, is released and acts on the fetoplacental unit through the blood 35 , and 3) inflammatory mediators from an infected periodontal reservoir provoke problems in the fetoplacental unit 36 .
A number of biologically active mediators such as prostaglandin E2 (PgE2) and tumor necrosis factor alpha (TNF-α) are also involved in the normal pregnancy process 37 .
These mediators are raised to artificially high levels during infections and thus may foster premature labour 37 . Lipopolysaccharides from gram-negative anaerobes found in periodontal pockets trigger the release of PGE2 and TNF-α, which may, in turn, affect the course of pregnancy. Evidence to support this hypothesis has been obtained in rodent models. Pregnant women who have periodontal disease may be seven times more likely to have a baby born too early and too small.
In addition, women experience "pregnancy gingivitis, 60-70 % ". However, women who have good oral hygiene have no this kind of gingivitis. Studies have demonstrated that treatment and early treatment of periodontal disease can reduce the patient's overall inflammatory burden, and dental treatment consideration at the same time informs the patient 38 .

Osteoporosis
Although osteoporosis is more prevalent in postmenopausal women, it can occur at any age and affects both men and women. The diagnosis of osteoporosis is made by the physician based on a test which measures bone density called dual energy Xray absorption (DXA). Several risk factors include small, thin body frame, family history of osteoporosis, diet low in calcium and vitamin D, inactive lifestyle, smoking, excessive alcohol consumption, and low estrogen levels. Some of these factors play a role in the progression of periodontal disease and tooth loss.
Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to risk 39 . Estrogen deficiency after menopause and consequent loss of bone mineral density have been shown to be associated with increased rate of tooth loss. These relationships may be explained by increased severity of periodontal disease in estrogen deficiency 40,41 .
It has been shown that total body calcium and bone density was closely associated with mandibular bone density and several studies have demonstrated a close relationship between edentulism and systemic osteopenia. Certain data showed a clear relationship between osteoporosis and periodontal disease, and osteoporosis is considered as one of the risk factors for periodontal bone loss. Both osteoporosis and periodontal disease are chronic multifactor diseases with many genetic and behavioral risk factors and determinants. Both diseases can be successfully controlled by eliminating several risk factors. Estrogen replacement therapy can be protective against both postmenopausal osteoporosis and severe periodontitis in postmenopausal women. Tobacco smoking and diet are also important risk factors for both diseases and genetic factors have also been identified as important
Loša oralna higijena, oralna kolonizacija parodontalnih i respiratornih patogena povezani su sa nazokomijalnom upalom pluća . risk factors in the etiology of both diseases. Recent epidemiological and clinical data provide limited but convincing evidence suggesting an association between osteoporosis and periodontal disease, and many common risk factors could have been detected in the etiology of both diseases 42,41 .
Systemic osteoporosis develops due to bone loss resulting in bone brittleness. The similar features are seen in the jaw and alveolar bones even if the bone structure is different. One should remember that as periodontitis progresses it leads to the loss of attachment and alveolar bone. Hence, a patient with osteoporosis with low bone density of alveolar bones is more susceptible to rapid progression of periodontitis.

Periodontitis and pulmonary disease
Bacterial pneumonia, chronic bronchitis, emphysema, and chronic obstructive pulmonary disease may be adversely affected by oral microflora. Research confirms findings that periodontal disease may increase a person's risk for the respiratory disorder. Bacteria from the oral biofilm may be aspirated into the respiratory tract to influence the initiation and progression of systemic infection such as pneumonia. Patients with periodontal disease, defined by mean periodontal attachment loss, greater than 3mm, were found to have nearly a one-and-a-half time higher risk of pulmonary disease. A distinct trend was also noted that the lung function seemed to diminish with increased periodontal attachment loss 43 .
This suggests that periodontal disease activity may promote the progression of pulmonary diseases. Antibiotic-resistant strains of bacteria are emerging, and oropharyngeal flora and secretions are directly responsible for potential respiratory infection. Aspiration of oral bacteria may be responsible for exacerbation of pulmonary disease 44 . Based on these and previous research findings, it is conceivable that improved oral health may help prevent the progression of pulmonary disease. It is possible that periodontal bacteria could travel to the lungs through saliva or normal breathing and in some way promote lung infection. Another possibility is that the inflammation caused by periodontal disease may contribute to the inflammation of the lining of the lung airway, which limits the amount of air that passes to and from the lungs. Oral pathogens may serve as a reservoir for these respiratory infections and influence the bacterial flora of the lower bronchi 45 .
The study found that patients with respiratory diseases had worse periodontal health, suggesting a relationship between respiratory disease and periodontal disease. Researchers suspect that the presence of oral pathogens associated with periodontal disease may increase a patient's risk of developing or exacerbating respiratory disease. However, the additional studies are needed to more conclusively understand this link.
Poor oral health, oral colonization of periodontal and respiratory pathogens, all possibly influenced by periodontitis, are associated with nosocomial pneumonia. A direct causal relationship between periodontitis and pneumonia has not been established, however, based on the studies reviewed, here it seems that oral colonization by potential respiratory pathogens contributes to pulmonary infections 47,48 .
Improved oral hygiene has been shown to reduce the occurrence of nosocomial pneumonia, both in mechanically-ventilated hospital patients and non-ventilated nursing home residents. It appears that oral colonization by potential respiratory pathogens possibly fostered by periodontitis, and possibly by bacteria specific to the oral cavity or to periodontal diseases, contributes to pulmonary infections. Thus, oral hygiene will assume an even more important role in the care of high-risk subjects -patients in the hospital intensive care and the elderly. The present paper critically reviews the recent literature on the effect of oral biofilm and periodontitis on pneumonia.
The oral cavity may be an important source of bacteria that cause infections of the lungs. Dental plaque, a tooth-borne biofilm that initiates periodontal disease and dental caries may also influence the initiation and progression of pneumonia because of relocalization of the bacteria from the biofilm into the respiratory tract. Bacteria causing community-acquired pneumonia are typically species that normally colonize the oropharynx such as Streptococcus pneumoniae, Haemophilus influenzae, and Mycoplasma pneumoniae 49 .
In addition, most epidemiological studies have reported increased levels of plaque, calculus and gingival inflammation in populations with renal disease. Whether an increased prevalence and severity of periodontitis exist in the population with renal disease remains controversial. Periodontitis has been found to contribute to systemic inflammatory burden including the elevation of C-reactive protein in the general population. However, in view of the high rate of mortality from atherosclerotic complications, the strong association between increased inflammatory burden and atherosclerotic complications, and the possible contribution to systemic inflammation from periodontitis, the periodontal status of all chronic renal disease patients need be monitored carefully 52 .
The goal of the campaign must be to educate patients about periodontal infection and its associated general health risks. Oral health is often a good indicator of what is happening in the rest of the body. Therefore, a visit to a periodontologist may be very helpful. It is important for patients to have regular oral exams not only to maintain oral health, but to identify possible risks for serious medical conditions.
Recommendations for the dental clinician include: 1. Reducing the levels of periodontopathic flora by maintaining good home care and frequent periodontal maintenance. 2. Rising with chlorhexidine prior to denthal / periodonthal therapy. 3. Performing required periodontal therapies to stabilize the periodontium. 4. Consultation with the patient's physician for periodontal/dental or medical concerns 1 .

Conclusion
In this new millennium, dental practitioners are obligated to care for the patient's total health. They are able to see the links and potential dangers of periodontal and other oral infections for systemic health. Future research will help dentistry unravel the complex interactions between host susceptibility, immune response, genetic associations, behavioral components, and disease control. Dentists must not only treat localized oral infections but manage the risk that varies with each individual patient.