Bacteria ¡nöuce the disease process
Antigens Lipopolysaccharides
Host response: monocytes/macrophages, etc
Cylokines(IL-1,TNF-o
Recruiied cells: fibroblasts. endothelial and epithelial cells, etc
PGE, Matrix metallcproleinases
Bone Loss of résorption connective tissue
The International Journal of Periodontics & Restorative Dentis.tr' y 337
Changing Periodontal Paradigms: Therapeutic Innplications
Gary Greenstein, DDS, MS* Periodontal diseases are the result of Ira Lamster, DDS. MMSc** infectionsoftheperiodontJum.^They should be considered infections because there is a bacterial etiology Many paradigms concerning the epidemiology, pathogeoesis, and systemic and a subsequent immune response. impact oí penodontai diseases have been modified. For example, bacterial A microbial challenge often results in hioñims are essential to induce penodontitis, but their mere presence is not suffi- a subclinical infection because the cient to mitiate disease. Jt is also now recognized that the host response to these host response prevents the bacterial b/ofiims causes most of the destruction of the periodontal tissues. Code terminants challenge from reaching the thresh- that influence the clinical severity of the disease process (ficiude enw'ranmentai, old necessary to cause symptoms.^ genetic, and acquired factors. In general, the prevalence of advanced periodonti- However, when subgingival bacteria tfs and the incidence of disease progression are tower thar) previously believed. overwhelm the host response, tissue However, pen'odontitis remains the rnost common chronic illness, in addition, the destruction occurs; this is termed finding that acquired systemic diseases may predispose individuals to periodonti- pedodonta! disease. During the last tis, and conversely that periodontitis may be a risk factor for certain systemic dis- eases, fias expanded the scope of periodon tics. These changed paradigms and decade, numerous paradigms their consequences with regard to selecting therapies are discussed in this review regarding periodontal diseases have article. (Int J Periodontics Restorative Dent 2000;20:337-357.) been modified, including preva- lence, incidence of disease progres- sion, etiology, pathogenic mecha- nisms, predisposing factors, and impact on the systemic health of the patient. This article addresses these modified concepts and explores their therapeutic implications.
'Clinical Professor, Department of Period ontology. University of Prevalence of gingivitis Medicine and Dentistry New Jersey, Newark. New Jersey. and adult periodontitis 'Assistant Dean, Columbia School of Dentistry, New York, New York.
Reprint requests: Dr Gary Greenstein, 900 West Main Street, Freehold, Epidemiologie surveys have found New Jersey 07728. that gingivitis without accompanying
Volume 20, Number 4, 2000 338
^^^^™ InriHpnrp of diipasp pmqrpisinn in patiptitc with pprinrlnntitis' ^
% of patients No. of No. of Evaluation Disease activity deteriorating % of sites Study patients sites period ¡mo) threshold (mm) in > 1 site deteriorating Grbjc et al^° 75 11,466 6 2.5 41.3 0.99 Deas et al-' 21 2,094 9 2.0 90.0 6.1 Persson and Page^^ 25 200 24 2.0 40.0 10.7 Halazonetisetal^^ 55 24,720 5-12 1.75 42.0 5.0 Jeffcoatand Reddy^" 30 — 6 0.4 77.0 29.0
periodontitis affects 50% of adults studies often record measurements Incidence of disease over 18 years old and involves an at the line angles of the teeth, but progression average of 6 or more teeth per pa- the mid-proximal areas tend to dis- tient.^ Furthermore, most inflamed play deeper probing depths'^'"; The incidence of disease progres- sites do not progress to periodonti- and the use of survey teeth routinely sion will also be influenced by the tis,''"' This was documented in stud- misrepresents the prevalence of dis- standard that is selected to define ies that longitudinally monitored eased sites.'^" In addition, the stan- disease progression. The data pre- patients with gingivitis'* and in inves- dard used to define periodontitis sented in Table 1 suggest that a tigations that assessed the preva- dramatically impacts on the data. small number of sites in a limited lence of attachment loss in untreated For example, when Brown et aP^ sel- number of individuals manifests dis- populations,^'* and it was supported ected a 5-mm loss of clinical attach- ease progression during a defined by animal studies.' However, Löe^ ment at one or more sites as a period."'^°"^'' The following results concluded that gingivitis is often threshold to characterize periodon- can be deduced from the data; 0) associated with and precedes peri- titis, 12% ofthe study population less than 50% of individuals with odontitis. Therefore, elimination of had advanced periodontal disease. periodontitis manifested disease inflammation remains a critical ob- However, if a 3-mm standard was activity within 1 year; 0 around 5% jective of periodontal treatment be- employed (equivalent to 25% ofthe to 10% of diseased sites demon- cause the absence of inflammation is length of a maxillary molar root), strated deterioration within 1 to 2 a negative predictor of future clinical then 42% ofthe subjects had peri- years; and (3) approximately 20% of attachment loss,'''" odontitis; depending on the estab- the patients accounted for 60% of all The prevalence of moderate lished threshold used to define peri- sites that progressed. periodontitis in the adult population odontitis. the data change. Despite The finding that a small number is approximately 30%,^ and severe the impression that the prevalence of of individuals provides the majority of periodontitis afflicts approximately advanced periodontitis has de- sites demonstrating disease pro- 10% ofthe population. "-I s Unfor- creased during the past several de- gression supports the concept that tunately, these data underestimate cades, it still affects over 30 million all individuals are not equally sus- the occurrence of periodontitis for Americans and remains the most ceptible to periodontitis. Support for the following reasons: epidemiologic common chronic disease. this conclusion is provided by the
The International Journal of Periodontics & Resiorative Dentistry 339
study of Loe et al,* which monitored untreated patients in Sri Lanka during ••••• •gñgjfl Models of disease progression a 15-year period. This study assessed Model Mechanism a homogeneous population that did Continuous modeP' Slow, steady, progressive disease process not practice oral hygiene and had Episodic burst theory^*-" Irregular periods of exacerbation and remission no dental care, thereby providing an Synchronous burst Periods of exacerbation and remission during a unusual opportunity to monitor the theory^^ defined period Epidemiologie model^* Consistent with continuous disease aging process natural history of periodontal dis- that depends only on the duration of the process ease. They noted that 9% of the indi- Brownian motion or Random periodsof sharp bursts and/or remission can viduals developed severe periodon- stochastic model^^ occur, but underlying disease activity remains constant titis, 81% displayed moderate bone Random walking modeP' When observed at regular intervals, modei is similar to Brownian motion model loss, and 11% had gingivitis. These Fracturai modeP Multifactorial model,simulates disease advancing with data underscorethe need to identify age in bursts and remissions susceptible individuals and provide appropriate therapy.
Patterns of disease progression
Several models of disease progres- sion have been proposed to explain temporal patterns of tissue destruc- tion fiable 2).^"" Historically, it was believed that periodontitis resulted ithin a patient share a common experiencing bursts of disease pro- in a slow, continuous, and progres- ^^"^^ Studies that employed gression,^* Similarly, others note that sive deterioration of the periodon- large thresholds to identify disease a linear pattern is the most common tium.^^ However, this did not ac- progression may have spuriously model of tissue breakdown,-^'' One count for patterns of destnjction that supported the burst theory. For in- explanation isthat discrete episodes developed quickly, or for observed stance, in one study when both 0,4- of disease progression occur, but periods of remission. Subsequent mm and 2.4-mm standards for dis- these microbursts cannot be de- clinical studies suggested that dis- ease progression were used, the tected by clinicians. Therefore, over ease progression occurs as episodic number of sites deteriorating dur- time, the cumulative result appears bursts of activity with periods of re- ing a ó-month period was 29% and as a linear change. On the other mission.^*'^' Other models of dis- 2%, respectively.^^ Different thresh- hand, it is possible that large incre- ease progression listed in Table 2 olds not only resulted in altering the ments of attachment loss can hap- suggest that episodes of disease number of deteriorating sites, but it pen before destruction is contained progression may be superimposed was dear that rejection of small alter- by the host response. The various on linear changes.^^^° ations was misleading with respect models described in Table 2 explain Several authors question the sta- to identifying patterns of clinical at- a variety of clinical and radiographie tistical procedures used to support tachment loss. In that investigation, findings. Nevertheless, several pat- the episodic burst theory because use of the 0.4-mm threshold resulted terns of disease progression may disease progression at sites was in linear disease progression at 76% occur at different sites within the treated as independent events and of the deteriorating sites, and only same mouth or at the same site at not related to the fact that sites 12% of sites were characterized as different periods. Patterns of disease
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Fig 1 Ranking of suspected bacterial pathogens.'- Very strong Moderate A actinomycetemcomitans S ¡ntermedius P gingivalis P micros B fors y thus F nucleatum E corrodens Eubacteñum sp Strong P intermedia C rectus E nodatum Treponema sp
progression will be affected by a vari- microflora.' It has been estimated disease progression in untreated or ety of risk factors, the virulence of the that healthy sites (probing depths < treated patients.^'^^ Furthermore, infecting bacteria, and the suscepti- 3 mm) harbor 10^ microorganisms, even among sites diagnosed as dis- bility of the patient. At present, it whereas deep pockets (> 6 mm) may eased, the microbiota cannot be appears that no single model of dis- be inhabited by > 10^ bacteria.^^ used to forecast which areas will ease progression should be ac- Criteria used to identify putative undergo clinical attachment or alve- cepted as dogma. Therefore, to pre- pathogens associated with peri- olar bone loss.^^-''^ Bacteria are nec- clude any patterns of disease odontal diseases include their high essary to develop periodontal dis- progression from occurring, the main numbers in progressive lesions, the eases, but their presence alone is concern of clinicians should be elim- fact that their elimination or sup- not sufficient to predict disease ini- ination of inflammation and control pression is associated with a return to tiation or progression. For disease of identifiable risk factors. health, host response (antibody pro- progression to occur, certain criteria duction), virulence factors, and dis- must be satisfied; (1) susceptible ease progression in animal studies.^^ host; 0 pathogens present; C3) viru- Etiology: Bacterial Of the 500 species detected in the lent pathogens exceed a tolerable pathogens associated oral cavity, relatively few are corre- threshold for the host; (4) absence of with periodontitis lated with periodontal diseases. beneficial species; and (5) conducive Three bacteria are very strongly asso- environment.-^'' Diversity of bacteria ciated with periodontitis; Por- phyromonas gingivalis, Bacteroides More than 500 bacterial species forsythus, and Actinobacillus actino- Types of infectior^s have been identified in the oral cav- mycetemcomitans.^^ Other organ- ity of humans.^^ Approximately 150 isms listed in Fig 1 are considered to Most of the bacteria listed in Fig 1 to 200 different species can be be strongly or moderately associ- can inhabitecologic niches adjacent found in any individual's mouth,^^ ated with periodontal diseases.' to teeth without causing disease. and each periodontal pocket can However, the mere presence of bac- This is because of resistance of the contain 30 to 100 different types of teria cannot be used to predict future tooth-soft tissue interface, rapidly
The International Journal of Periodontics & Restorative Dentistry 341
responsive inflammatory cascade, with a variety of microenvironments recognized today that supragingival and specificity of the immune re- (different pH, Eh, etc), exhibit meta- plaque control can affect subgingival sponse. When there is a disruption of bolic cooperativity, share a primitive bacterial proliferation in periodon- the host-parasite equilibrium, a poly- circulatory system, and develop an tal crevices that are less than 5 microbial infection overwhelms the exopolysaccharide matrix for mutual mm.^'-^^ Therefore, optimal plaque host defenses and the disease pro- protection.''^-''^ This organization control is advantageous because it cess is considered an opportunistic can prevent drugs from penetrating impedes supragingival plaque from infection.'^'* The term opportunistic into the biofilm, and it has been esti- providing nutrients and bacterial infection denotes that indigenous mated that concentrations that are seeding of the subgingival area. bacteria (normal residents) induce effective against plani
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relative risk that sites will manifest ^^^^^1 Relative risk for disease progression*' disease progression.' Therefore, it
Disease threshold Relative is prudent to reduce pathogenic Bacteria (No. of bacteria) risk levels to below the thresholds listed Pgingivalis 2.2 in Table 3. 10* 4.1 A acrinomycetemcomitans 10^ 3.2 10^ 4.3 Endogenous vs exogenous 5 intermedius 2.4 10^ 3.0 bacteria "Attachment loss >2 mm in 2-mo period Most bacteria found within the oral cavity are considered endogenous; however, it is unresolved as to whether P gingivalis and A actir^o- mycetemcom/tans are endogenous or exogenous.^' Several lines of evi- dence suggest that P gingivaiis and A act/nomycetemcomitans are ex- ogenous: they may induce an anti- body response, they are often asso- ciated with disease, and they are not commonly found in periodontally healthy individuals at levels that ex- ceed 10^ organisms per sample.*° In contrast, factors indicating that they Bacteria! invasion of tissues Bacterial thresholds are endogenous include: a relatively large percentage of the population, Some microbes found within bio- When the microbial flora associated including periodontally healthy in- films can invade periodontal tissues. with health and gingivitis are com- dividuals, may harbor these bacteria For instance, P gingivalis and A actin- pared, gingivitis patients demon- at very low levels (less than 10^ per omycetemcomitans have been strate an increased microbial load sample), and there are numerous found within epithelial cells,^^'^* but (10^ to 10* organisms per site) and clonal types of these bacteria.^^ the relationship between bacterial an elevated percentage of gram- invasion of tissue and disease pro- negative bacteria (15% to 50%).'"' gression is unclear.'" It has not been The bacterial load is approximately Cionality determined whether tissue invasion 10^ to 10^ microorganisms per site is directly related to disease recur- when periodontitis is present, con- Clonality denotes that within a spe- rence. Nevertheless, infections asso- sisting mostly of gram-negative, an- cies there are subspecies that are ciated with A actmomyceiem- aerobic bacteria.''^ As previously in- genetically different, eg, there are at comitans are difficult to manage dicated, bacteria cannot be used least 32 clonal types of P gingivaíié^ nonsurgically or surgically, and it to predict which sites will undergo and 10 types of A actinomycetem- often is necessary to administer sys- disease progression; however, comitans.^^ Usually multiple clonal temic antibiotics to suppress this for some pathogens bacterial load types are indicative of endogenous thresholds reflect an increased bacteria.^' The occurrence of
The International Journal of Periodontics & Restorative Dentistry 343
multiple clonal types provides an bacteria may reside in different fam- explanation as to why certain indi- ily members, thereby providing viduals colonized with the same strong evidence that bacterial trans- species of bacteria may or may not mission occurred. At present, the manifest signs of disease. For data indicate that microorganisms instance, a microbiologie test may can be transferred between detect elevated levels of A actino- spouses*^'*'' and from parents to mycetemcomitans in a healthy pa- children.^^'^^ However, the inci- tient. This may be because of detec- dence of transmission varies, and it tion of a nonvirulent cicnal type. should not be assumed that trans- This creates a dilemma because rou- fer of bacteria will result in disease tine microbiologie assessments do initiation. Furthermore, transfer of not differentiate between clones of bacteria should not be interpreted a bacterial species, nor do they to mean that periodontitis is conta- assess pathogenicity. Thus, clinicians gious for the following reasons: must rely on clinical and radi- bacteria are not easily transmitted ographie manifestations of disease between spouses or from parents to to signal that therapy is needed. children, many healthy individuals Furthermore, since most potential harbor potential pathogens, and pathogens are considered endoge- transfer of bacteria does not nec- nous and thus elimination is not fea- essarily result in disease,^' There- sible, therapy needs to be directed fore, community efforts to eradi- at suppression to facilitate man- cate specific types of bacteria are agement ofthe bacterial challenge not needed. On the other hand, it by the host response,^' In contrast, would be prudent to Increase clin- if an organism can be labeled as ical monitoring and possibly micro- exogenous, then treatment should biologic testing of individuals ex- be aimed at its eradication.'''' To posed to a close family member ensure that alleged pathogens have with advanced periodontitis, espe- been reduced below levels that are cially if there is an extended family detectable by culturing (10^ bacte- history of increased susceptibility ria), it may be worthwhile in certain to periodontitis. individuals to culture after therapy as opposed to prior to treatment.
Transmission of bacteria
DNA fingerprinting techniques (ie, reduction endonuclease analysis) have been used to assess routes of transmission of putative periodon- tal pathogens.^' Investigators con- firm that the same clonal types of
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Fig 2 New classification of periodontal diseases ¡for a complete listing, see Ar mi tsge"). i tora Jmed by systemic factois, eg, puberty, menstrual cycle, pregnancy by medications -Gingivitis mooified by malnutrition •Non piaque-induceö gingival lesions, eg, viral, fungal, genetic, mucocutaneous, allergic
•Ctironic periodontitis (formerly called adult periodontitis) Seventy: mild {< 3 mm CAL), moderate (3-4 mm CAL), severe (> 5 mm CAL): char- acterized by the extent of CAL (clinical attachment less] Amount of destruction consistent with local factors Associated with variable microbial patterns Slow to moderate disease progression, but may have periods of rapid progression Can occur at any age, and there oan be localized or generalized forms •Aggressive periodontitis, localized and generalized (formerly called early-onset peri- odonfitis, which inoludes juvenile, prepubertal, and rapid-progress penodontitis) Rapid attachment loss and bone desiruotior Amount of microbial deposits inoonsistent with severity of tissue destruction Familial aggregation Frequently associated with A actinomycelemcomilans infections Localized affects molars and incisors Generalized affeots molars, incisors, and at least 3 other teeth
•Periodontitis as a manifesfalion of systemic diseases, eg, hématologie or genetic disorders •Necrotizing periodontal diseases Neorotizing ulcerative gingivitis Necrotizing ulcerative periodontitis •Periodontal abcesses •Periodontitis associated with endodontic lesions •Developmental or acquired deformities, eg, mucogingival deformities, occlusal trauma
Pathogenesis of stress, systemic diseases),*^ The and progressi periodontal disease complex interplay among the micro- The initial phase of disease occurs bial challenge, the intrinsic host re- when a bacterial challenge over- The term periodontitis denotes a sponse, and disease modifiers deter- whelms the neutrophils, B, and T family of diseases that has similar mines the clinical manifestations and lymphocytes. Then the bacteria, in histopathologic features, pathways severity of periodontal disease. Dis- particular the gram-negative spe- of destruction, and healing mecha- ease modifiers can affect host re- cies, release cell wall components nisms. However, disease entities sponse, tissue homeostasis, tissue in vesicles that contain lipopolysac- listed in Fig 2 differ with regard to repair, age of onset, patterns of de- charides, etc. When these vesicles their etiology, natural history, pro- struction, rate of disease progres- enterthetissues, they induce a host gression, and response to therapy,*^' sion, response to therapy, severity of response in which initially mono- It is now recognized that the disease disease, and frequency of disease cytes/macrophages release cyto- process may be modified by genetic recurrence,*' kines (proinflammatory mediators) factors, environmental factors (eg, The following sequence of such as interleukin (IL)-1 and tumor smoking), and acquired factors (eg. events characterizes the initiation necrosisfactor(TNF]-a(Fig3],These
DI Periodontics & Restorative Dentistry 345
Fig 3 Model for path ogenesis of peri- odontal diseases. Bacteria induce the disease process
Antigens Lipopolysaccharides
Host response' monocyles/macrophages, etc
Cylokines(IL-i,TNF-o)
• Recmiled cells: fibroblasts, endothelial and epilhelial cells, etc
PGEj Matrix metalloproteinases
• Bone Loss of résorption connective tissue
mediators recruit other cells (eg, parameters (eg, clinical attachment biochemical differentiation among fibroblasts, junctional epithelium, level). Nevertheless, a biochemical aspects of the disease process. endothelium) to produce prosta- shift may signal the transition from In general, feedback mecha- glandin E^ (PGE^), which are re- gingivitis to periodontitis. Gingivitis nisms regulate the inflammatory sponsible for bone destruction and is characterized by increased leuko- response, thereby modulating the matrix metalloproteinases that des- triene B^ levels derived from de- response to bacteria, tissue turn- troy connective tissue. IL-ó, IL-1ß, granulating neutrophils in the gin- over, and facilitating repair An exu- and TNF-a also participate in alveo- gival crevicularfluid.^^'*' In contrast, berant release of pro inflammatory lar bone loss, but to a lesser extent periodontitis lesions manifest in- mediators results in uncoupling of thanPGE^.*' creased levels of PGEj, IL-1, and anabolic and catabolic processes, Gingivitis is the initial lesion in TNF-a, which reflect activation of which causes tissue destruction. the development of periodontitis-^ macrophages and lymphocytes.^-^ Subsequently, the host usually However, differentiating between These findings may lead to the restores the host-parasite equilib- gingivitis and periodontitis may be development of chairside tests to rium, and the perceived burst of dis- difficult when assessing clinical detect these mediators and provide ease progression is replaced with a
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phase of remission. Interestingly, Periodonta! destructive Recurrent vs refractory there appears to be a radius of influ- syndromes periodontitis ence induced by the pathogenic biofilm.*' Several investigators Periodontitis reflects a family of peri- Usually periodontal pathogens can hypothesize that breakdown occurs odontal diseases that may be epi- only be suppressed, thereby result- when the biofilm plaque front is sodic, site specific, and induced by a ing in microbial persistence even within 2.5 mm of the connective tis- variety of microorganisms.'-'^ The after clinically successful treat- sue attachment""^ It was suggested various clinical forms of periodontitis ment.''^' This provides a partial that if the bacterial challenge is not may share common histopathologic explanation as to why recurrent peH- controlled by host defenses, the tis- mechanisms and manifest common odontitis can occur despite appar- sues recede away from the noxious clinical signs of pathosis.*' However, ently successful treatment. However, stimulus, which is perceived by clin- their etiologic and triggering mech- the term recurrent periodontitis, icians as development of pocketing anisms for disease progression still which applies to sites and patients, or bursts of disease progression. need clarification. For example, should be differentiated from refrac- This pattern can then be repeated investigators demonstrated that the tory periodontitis, which indicates when the biofilm again encroaches bacteria detected in lesions that were that a patient (not a site) is nonre- on the junctional epithelium and losing clinical attachment (> 2 mm) sponsive to conventional treatment. connective tissue. Thus, even dis- and those that were stable were not Characteristics employed to differ- eased sites that are not progressing different.^^'*'^ This finding under- entiate between these terms are should be treated to break this chain scores that the precise factors that listed in Table 4.'^ It should be noted of events. This concept is supported by evidence that deeper probing upset the host-parasite balance are that refractory periodontitis requires sites harbor more bacteria, are more not defined. Therefore, the term antibiotic therapy in conjunction with often associated with inflammation, periodontal destructive syndromes conventional treatment."'' and are more prone to additional may appropriately describe different clinical attachment loss in treated types of periodontitis' ' ; the term syn- and untreated patients.''' drome is used to label a pattern of Risk factors clinical signs and symptoms whose Suppression of the bacterial etiologies are not fully understood. The clinical expression of periodon- challenge remains the sine qua non tal disease is modified by risk factors of treatment. Nevertheless, recog- that can be classified as acquired nition that the host response to Tooth ¡OSS (eg, diabetes), environmental (eg, pathogens is mainly responsible for smoking), an tissue destruction has provided an The concept that tooth loss after the impetus to explore the potential of age of 35 is mainly caused by peri- host response modification as an odontal diseases is no longer valid. Diabetes adjunct to conventional periodontal Recent studies note that caries, not therapy. Preliminary data suggest periodontitis, is the principal reason There are 2 major types of diabetes: that inhibition of matrix metallopro- for extractions in all patients except teinases by administration of tetra- Type 1-insulin dependent and Type the very oldest.'^''" cycline analogues or inhibition of 2-non insulin dependent. Type 1 is prostanoids with nonsteroidal anti- characterized by reduction of insulin inflammatory drugs (NSAID, eg, flur- caused by destruction of pancreatic biprofen) may be helpful in the man- beta cells, whereas in Type 2 there is agement of certain patients.''^ resistance of target tissues to the action of insulin.^* Investigators have
The International Journal of Periodontics S. Restorative Dentistry 347
^^^^9 Characteristics of recurrent and refractory periodontitis^^ Characteristic Recurrent periodontitis Refractory periodontitis Definition Sites successfully treated but disease returns; Sites do not respond to conventional therapy; usually may refer to sites or patients refers to patients but may refer to sites Phase of therapy May be because of inadequate therapy during May be because of inadequate therapy during active maintenance or no maintenance treatment or other factors Etiology May be because of reinfection with microbes that May be because of infection with tissue-invasive were suppressed but not eliminated, reinfection microbes that cannot be eliminated with conven- with eliminated organisms,ornew bacteria tional therapy or because of immunoincompetence Immune system Immunocompetent May not be immunocompetent Antibiotic therapy Not usually needed Usually needed
indicated that diabetics have a 2 to and metabolic waste removal. It also performed for the 1996 World 3 times greater chance of develop- results in an increased secretion of Workshop in Periodontics indicated ing periodontitis than nondiabet- proinflammatory cytokines [IL-1ß, that smokers have a 2.8 times 1^-5 68.76,77 Q^ ^|^g ^^^^^ hand, pa- TNF-ß), impaired neutrophil chemo- greater chance of developing peri- tients whose diabetes is medically taxis, and altered connective tissue odontitis than nonsmokers.^^ To- managed respond normally to ther- meta bo I i sm.*^'^* These alterations bacco use is also related to disease apy and are not at increased risk for may contribute to a predisposition to recurrence and decreased response pen'odontitis.'^ the initiation and increased severity to therapy.^^'^"" The underlying No difference in the subgingival of periodontal disease and delayed mechanism has not been defined, microflora was detected among dia- wound healing among diabetics. but it may be related to an increased betics and nondiabetics.™'" How- The clinical finding of rapid changes bacterial load detected subgingi- ever, itwas suggested that diabetics in the periodontal status of patients vally.^^ This may occur because of respond differently to pathogens with diabetes should increase the decreased oxygen tension, which because of impaired host defenses, clinician's suspicion of a change in encourages the growth of peri- thereby making them more suscep- the metabolic status of the patient, odontal pathogens. Systemic alter- tible to infections.''^'* This has been and a medical consultation may be ations in the host response among attributed to vascular changes, poty- required. smokers include impaired chemo- morphonuclear leukocyte dysfunc- taxis and phagocytosis by neu- tion, and altered immune regula- trophils, reduced antibody produc- tion.*^'''' Vascular changes seen in Smoking tion, and increased circulating levels diabetics are caused by prolonged of TiMF-ö.^S'36,s7 Smoking is also as- exposure to hyperglycemia. This re- Tobacco smoking is a major risk fac- sociated with delayed healing after sults in formation of advanced glyca- torfordeveloping severe periodon- nonsurgical^^ and surgical therapy.^' tion endproducts (nonenzymatic gly- titis.*^ Individuals classified as light Smoking appears to be associ- cated proteins and lipids), which smokers and heavy smokers have a ated with a reduction in tissue induce irregularthickness and rigid- greaterchance of developing severe inflammation and bleeding on prob- ity of blood vessels that impair leuko- periodontitis (2 and 7 times greater, ing because of nicotine-induced cyte diapedesis, oxygen diffusion. respectively).^°^' A meta-analysis vasoconstriction of blood vessels
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subjacent to the junctional epithe- that suggests that this may be true status. Additional studies are iium.''^ This can mask severe pock- is beginning to emerge. For exam- needed to determine if hormone- eting and alveolar bone loss. ple, women with osteoporosis man- replacement therapy in post- Clinicians should counsel patients ifest adverse effects on mandibular menopausal women should be regarding the negative impact of bone mass''' and crestal bone advocated both to reduce the signs smoking on their periodontal health. height,'^ and they demonstrate of osteoporosis and to help in the Since smokers are high-risk individ- more clinical attachment loss than management of periodontitis. uals for additional disease recur- normal women.*** Furthermore, rence, they should be monitored estrogen-deficient women have more closely and provided with quar- more bleeding on probing and less Genetics terly maintenance visits to help them alveolar bone density than estrogen- manage their bacterial challenge. sufficient women.'^"'^ In addition, Several lines of evidence indicate hormone-replacement therapy re- that genetically determined suscep- sults in greater retention of teeth'™ tibility is a critical determinant in the Psychologic stress and is associated with a reduction in clinical manifestations of periodon- clinical attachment loss."*' tal diseases: studies addressing fam- Several studies suggest that stress Mechanisms that Induce post- ily aggregation, formal genetic stud- can reduce the efficacy of the im- menopausal women with osteo- ies of different forms of early-onset mune response. There is strong his- porosis to lose bone may also pre- periodontitis, association with cer- torical evidence that the develop- dispose individuals to develop tain Mendellian inherited diseases ment of acute necrotizing ulceratlve periodontitis. This could be attrib- (eg, cyclic neutropenia), twin studies, gingivitis is at least in part stress re- uted to decreased levels of estro- and the finding that certain genetic lated.*" However, at present there gen, which normally has an ana- polymorphisms are associated with are no longitudinal psychoneuroim- bolic effect on osteoblast-like an abnormal host response."'^•"^* munologic studies that address cells.'°^ Estrogen also downregu- Studies that address the familial ag- alterations in host defenses to peri- lates IL-6, which converts mono- gregation of early-onset periodonti- odontal organisms In patients expe- cytes into osteoclasts.'"^ Thus, a tis support the idea that there is riencing psychoemotional stress.*^ reduction of estrogen results in less autosomal-dominant inheritance for A possible mechanism for stress to bone deposition and Increased early-onset periodontitis.'°^'"^' influence pathogenesis could be osteoclastic bone résorption. Other genetically transmitted dis- CO rti costero ids exerting an inhibitory Additional evidence supporting the eases (eg, cyclic neutropenia] result effect on Inflammatory cells.'^'^ concept that osteoporosis is a risk in decreased numbers and altered Stress is a potential risk factor for factor for periodontitis was pro- phagocytic function of neutrophils, periodontal disease, but the under- vided by Jeffcoat,"*" In a clinical predisposing individuals to develop lying mechanisms need to be thor- trial, scaling and root planing were periodontitis.'™ Enhanced suscep- oughly evaluated.*^ administered to all patients plus bis- tibility may also be because of a phosphonate alendronate, an genetically determined reduced approved osteoporosis therapy, capacity to produce gamma G im- Osteoporosis was administered to half of the pa- munoglobin (lgG)2 during peri- tients.'"" The group receiving the odontal Infections'^^ or altered Currently, the data that estrogen antiosteoporosis drug had reduced monocyte/macrophage function deficiency, which causes osteoporo- loss of bone height and density, that results in Increased release sis, isa risk factor for periodontltis are thus establishing a link between of prolnflammatory mediators, not con elusive,'^^ However, evidence osteoporosis and periodontal thereby enhancing predisposition to
The International Journal of Periodantics & Restorative Dentistry 349
disease, •"''•"° It has been noted that severe, painful, rapidly progressive patients should be provided with fre- the data found in twin studies sug- periodontal lesion referred to as quent supportive periodontal ther- gest that heredity can account for necrotizing ulcerative periodontitis apy to help reduce their oral bac- 50% of the enhanced risk for peri- develops in < 5% of HIV-infected terial challenge while they receive odontitis,'" patients.^ '"' It is more common for an appropriate therapy, ie, protease A recent study concluded that HIV-infected individual with peri- inhibitors, from their physicians. susceptibility to severe periodontitis odontitis to manifest indistinguish- is significantly enhanced when able radiographie and clinical signs genetic polymorphism of both IL-1a of periodontitis,*^ and the microflora Systemic effects of and IL-1ß genes is detected,^^ This in these individuals is similar to that periodontal diseases is based on the supposition that in other periodontitis patients,"^ these polymorphisms induce an These patients may have elevated While systemic diseases are a risk overproduction of interleukins, levels of Candida, but the relation- factor for the development of peri- thereby inducing greater destruction ship of subgingival fungal infections odontitis, emerging data from case of periodontal tissues. Another and periodontal disease initiation or history and cross-sectional studies investigation found that a genetic progression is unclear."* indicate that periodontitis may be a polymorphism of the IL-1ß gene The predisposition of HIV pa- risk factor for systemic diseases,'* alone is sufficient to induce increased tients to develop periodontitis can However, it should be noted that as- risk for periodontitis,"^ These find- be attributed to alterations of inflam- sociations based on these types of ings need to be examined in longi- matory cell and immune cell func- investigations are not as powerful as tudinal studies before specific ther- tions."''"' For instance, it was re- data from longitudinal or interven- apeutic approaches are suggested. ported that the recruitment of tional studies.^^ Additional studies There appear to be complex inter- polymorphonuclear neutrophils are needed before preliminary find- actions between multiple genes and (PMN) is Impaired in seropositive ings are used to develop treatment environmental factors that interact individuals, and there is a signifi- recommendations for patients with to induce disease and modify its cantly reduced number of T cells certain systemic diseases. At pre- expression. As these genes are dis- (lymphocytes)."* In addition, séro- sent, there should be prudent dis- covered, it may be possible to inte- positive individuals demonstrate ele- semination of information and judi- grate their identification into a risk vated levels of IL-1 ß, which suggests cious therapeutic recommendations profile that will help identify individ- an altered immune response,"'' based on the data linking periodon- uals who are susceptible to peri- The clinical symptoms mani- tal diseases with systemic maladies. odontitis and early tooth loss.'^^"^ fested by some seropositive patients (eg, lineargingival erythema, necro- tizing ulcerative gingivitis, necrotizing Card/ovascufar disease HIV ulcerative periodontitis) are different from those usually seen in patients Several studies indicate that there is Individuals infected with the human with adult periodontitis. Thus, it was an increased risk of developing var- immunodeficiency virus (HIV) and suggested that HIV infections should ious forms of cardiovascular disease others in which the infection has pro- not be considered a modifier of gin- among individuals with periodonti- gressed to acquired immunodefi- givitis or periodontitis, but rather ^¡5 113-122-|-f,g strength of this asso- ciency syndrome (AIDS) may be at they should be considered a different ciation needs to be characterized greater risk of developing peri- type of periodontal disease.*^ This as moderate (Table 5), The biologic odontal diseases than individuals issue is unresolved. Regardless of basis for the association be- who are not HIV séropositive.'^^ A which position is correct, these tween cardiovascular disease and
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Risk of developing cardiovascular disease based on periodontal findings
Study Design Association Measured DeStefano et al"'' Cohort Plaque Index, oral hygiene index Relative risk 1.2 Death caused by CHD Relative risk 1.7 Joshipuraetal"^ Cohort Tooth loss in men with periodontal disease and CHD Relative ri5k 1,7 Beck et al'^" Cohort Pocket depth, bone levels, and new CHD; fatal CHD and stroke Odds ratio 1.5,1,9,2.8 Gencoet al'^' Cohort Bone loss and new CHD Odds ratio 2.7 CHD = coronary heart disease.
periodontal infections is presently and periodontitis, but this should calculated in this relatively small unclear.^^^'^^^ However, several not be interpreted to indicate a case-control study.'^' Thus, clinicians mechanisms to explain this relation- causal relationship. Additional should be cautious when interpret- ship have been proposed. For exam- studies, in particular intervention ing these data. ple, dissemination of oral bacteria studies, are needed to determine It is believed that a variety of through the vasculature or elevated if prevention or treatment of peri- biologically active molecules, Süch circulatory levels of proinflammatory odontitis will decrease the inci- as PGEj and TNF-a, are increased in cytokines induced by the periodon- dence of cardiovascular diseases. association with infections, and tal infection can cause modification these molecules may foster prema- of the vascular endothelium.^^''^^ ture labor. Another case-control This can ultimately promote devel- Pregnancy compHcatiorjs study [n = 44) found that gingival opment of fatty streaks and arthero- crevicular fluid levels of PGE^ are 2 sclerotic lesions that may cause coro- Approximately 7,3% of babies born times higher in mothers of low- nary thrombosis, ischémie heart in the United States are considered birth weight babies.'^' Furthermore, disease, or a stroke. Another model preterm low-birth weight babies [< microbial data indicate that bacter- suggests that myocardial ischemia, 2,500 g). Preliminary data in a ham- ial pathogens are detected at higher which is often preceded by acute ster modeP^* and several human levels in mothers of preterm thromboembolitic events, may be clinical trials suggest that periodon- low-birth weight babies than in induced by several bacterial species titis may be associated with adverse mothers of normal-birth weight found in dental plaque (eg. Strepto- pregnancy outcomes. A re- babies.'^^ This additional bacterial coccus sanguis, P gingivalis).^'"''^^^ cent study indicated that among 124 burden may account for the in- These organisms are capable of pro- women there was a 7 times greater creased level of proinflammatory moting the aggregation of platelets chance of a low-birthweight baby in mediators found in mothers giving (confirmed in a rabbit model), which individuals with greater clinical birth to low-birth weight babies. may result in development of emboli attachment loss (the mean value in Large studies are needed to verify and thereby possibly predispose the2groupswas0.3mm,3.1 mmvs the link between low-birth weight individuals to thrombogenic 2.8 mm).'^^ However, the authors babies and periodontal disease. In events.'^^ In general, the data sup- cautioned that odds ratios from addition, intervention studies are port the contention that there is future large longitudinal studies will needed to determine whether peri- an association between the inci- probably be lower than the mag- odontal therapy can reduce the inci- dence of cardiovascular disease nitude of the odds ratio that was dence of low-birth weight babies.
The International Journal of Periodontics & Restorative Dentistry 351
Diabetes with regard to pocket reduction and gain of clinical attachment are listed Diabetes is a risk factor for peri- in Table 6. Adjunctive, single epi- odontitis, and preliminary data sug- sodes of subgingival irrigation do gest that periodontitis may bea risk not enhance root planing, whereas factorfor diabetes. Two studies have supragingival irrigation with an irri- noted that periodontal therapy, gator does reduce gingivitis among including scaling and root planing individuals who do not practice Opti- and antibiotics, improves metabolic mal oral hygiene.'^^ In general, both control among diabetics.'^*"'^' This local and systemically delivered an- concept is supported by the finding tibiotics are reserved for patients that patients manifest reduced levels who do not respond to conventional of glycated hemoglobin and a re- treatment.''"''^^''^^ Empirical selec- duced need for insulin in the treat- tion of the applied drugs is common ment of their diabetes subsequent practice; however, to avoid admin- to periodontal therapy. These data istration of ineffective medicaments, can be interpreted to suggest that bacterial sensitivity testing can be physicians should consider the peri- used to guide drug therapy.'^* Sub- odontal status of diabetic patients sequent to active treatment, sup- having difficulty with glycémie con- portive periodontal therapy usually trol and that periodontal therapy ensures that the baaerial challenge may be a necessary adjunctive ther- will be kept below the level needed apy in the treatment of certain dia- to initiate progressive disease. How- betic patients.'^^ ever, no precise interval between maintenance visits suits all patients; therefore, scheduling supportive Periodontal therapies periodontal therapy visits needs to be titrated on an individual basis. Periodontal treatment consists of The need for surgical periodon- several components: preventive, tal treatment is dictated by the active care, and supportive peri- severity of the defects being treated, odontal therapy. Counseling pa- the response to nonsurgical therapy, tients with regard to appropriate oral and the desired clinical outcome {ie, hygiene to prevent the onset of any regeneration of lost support).'^^'''^' form of periodontal disease is an in- Surgical techniques employing bone tegral part of therapy and remains a grafts and guided tissue regenera- critical determinant for long-term tion are frequently used in severe patient management. Active treat- lesions.'^^"'"° Table 6 lists mean ment consists of antiinflammatory results that can be expected after and regenerative therapy. Scaling different types of surgical and non- and root planing is an effective treat- ment in the management of patients During the last decade, numer- with gingivitis and early to moderate ous studies have examined the titis.'^^-'-^" Expected results potential application of polypeptide
Volume 20, Number 4, 2000 ^^^^^1 Kpprpspntativp rpsiiltsotflittprent Therapies immr
Pocket Gain of clinical Bone Procedure reduction attachment fill Open-flap debridement^'""* 3.0 1.5 1.1 Demineralized freeze-dried bone graft^'''" 2.5 2.1 2.2 Guided tÍ5sue regeneration"'"' 5.2 4.2 3.2 Scaling and root planing'" Pockets 4-6 mm 1.29 0.55 — Pockets > 7 mm 2.16 1.29 — Tetracycline fibers (Actisite, Procter & Gamble) + scaling and root planing''" Pockets 4-6 mm 1.0 1.1 — Pockets >7 mm 2.1 1.2 — Chlorhexidinechip (Periochip, Astra) + scaling and root planing'''^ 0.95 0.65 — Doxycycline polymer (Atridox.Block Drug)''*^ 1.3 0.8 — Subantimicrobial doxycycline (Periostat,CollaGenex)'''^ +scaling and root planing Pockets 4-Ö mm 1.03 0.95 — Pockets > 7 mm 1.68 1.55 — Enamel matrix protein (Emdogain,Biora)'''^ 3.1 2.2 2.6 'Re5ult5 are representative dala taken from large cljnical trials. "•Mean results based on a meta-analysis.
groviith and differentiation factors for This drug blocksthe action of certain are infections that may have both the treatment of periodontitis. These matrix metalloproteinases (MMP) local and systemic consequences. are a class of biologic mediators that that are involved in tissue destruc- Accordingly, elimination of peri- regulate cellular events in tissue re- tion {MMP-8, MMP-9 from neutro- odontal Infections facilitates reten- pair [ie, cell proliferation, chemo- phils). Preliminary data indicate that tion of teeth afflicted with peri- taxis). Examples of these factors in- this treatment provides an adjunctive odontitis and may preclude or clude platelet-, epidermal-, and aid when used with root planing reduce problems associated with cementum-derived growth factors; (Table 6).''''' Thus, alteration of the systemic maladies. To enhance man- bone morphogenic proteins (BiVlP 1 host response may prove to be a agement of periodontal patients, it to 12); etc."'* At present, none of very effective management tool in is important that clinicians consider these growth factors has received certain patients who do not respond risk factors for periodontitis, espe- US Food and Drug Administration well to conventional and antibiotic cially systemic modifiers of the dis- (FDA) approval.'"'* However, one therapy. ease process. In this regard, peri- product that employs enamel matrix odontal patients may require proteins has been approved and is medical consultation. probably the forerunner of many Conclusion Ultimately, the goal of peri- products that will eventually be intro- odontal therapy is retention of teeth duced to enhance regenerative ther- Traditional paradigms concerning in health and comfort. Achievement apy. "^ periodontal diseases are in the pro- of this goal can be optimized if our A new therapy for periodontal cess of being modified. These diagnostic efforts and therapies are diseases that does not rely on con- changes are expanding the scope biologically based, ie, control of in- trolling the bacterial challenge is and implications of periodontal diag- fection and inflammation, and incor- subantimicrobial dosing with doxy- nosis and therapy. It is currently rec- porate new knowledge concerning cycline (20 mg twice a day)." ognized that periodontal diseases changed periodontal paradigms.
The International Journal of Periodontics &. Restorative Dentistry 353
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Potential pathogenic Treatment of intrabony detects by dif- mechanisms of periodontitis-associated ferent surgical procedures. A literature pregnancy complications. Ann review, J Periodontol 1998,69:303-313. Periodontol 1998;3:233-250. UI.Drisko CL, Cobb CM, Killoy WJ, 128. Offenbacher S, Katz V, Ferlik G, Collins Michalomicz BS, Pihlstrom BL, Lowen- J, Boyd D, Maynor G, et al. Periodontal guth RA.etal. Evaluation of periodontal infection as a possible risk factor for treatments using controlled-release preterm low birth weight. J Pericidontol tetracycline fibers: Clinical response J 1996;ó7(suppl 10¡:n03-1113. Periodontol 1995;66:692-699 129. Dasansyake AP. Poor periodontal health 142.Jeffcoat MK, Bray KS, Ciancio SG, of the pregnant woman as a risk factor Dentino AR, Fine DH, Gordon JM. for low birth weight. Ann Periodontol Adjunctive use of a sub-gingival con- 1998,3:200-212. trolled-release chlorhexidine chip 130. Miller LS, Manwell MA, Newbold D, reduces probing depth and improves Reding ME, Rasheed A, Bbdgett J, attachment level compared with scaling Kornman KS. The relationship between and root planing alone. J Periodontol reduction in pericidontol inflammation 1998:69:989-997. and diabetes control: A report of 9 cases. 143. Garrett S, Johnson L, Drisko CH, Adams J Penodontol 1992,63:643-843. DF, Bandt C, Beiswsnger B, et al. Two 131. Grossi SG. Skrepcinski FB, DeCaro T, multi-center studies evaluating locally Zambón JJ, Cummins D, Genco RJ. delivered doxycycline hyclate, placebo Response to periodontal therapy in dia- control, oral hygiene, and scaling and betics and smokers, J Periodontol root planing in the treatment of peri- 199é;67(5uppl 101:1094-1102. odontitjs. J Periodontol 1999:70: 490-S03. 132. Grossi SG, Genco R. Periodontal disease and diabetes niellitus: A two way rela- 144. Caton JG. Evaluation of Penostat for tionship. Ann Periodontol 1998;3:51-61. patient management. 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