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A PEER-REVIEWED PUBLICATIONA PEER-REVIEWED PUBLICATION

DENTAL LEARNING

— A REVIEW—

Bio� lm,the host response

and treatmentin periodontal disease

Fiona M. Collins, BDS, MBA, MA

LEARNING OBJECTIVES

The overall goal of this article is to provide information on periodontal disease and the role of bio� lm in its development and progression. After completing the article, the reader will be able to:

1. Review the role of bio� lm in periodontal disease;

2. Describe the pathogenesis of periodontal disease, destructive and protective chemical mediators;

3. List and describe risk factors; and,

4. Review options for treating chronic periodontitis and their ef� cacy.

SPONSOR/PROVIDER: This is a Dental Learning, LLC continuing education activity. COMMERCIAL SUPPORTER: This course has been made possible through an unrestricted educational grant from ORAPHARMA. DESIGNATION STATEMENTS: Dental Learning, LLC is an ADA CERP recognized provider. ADA CERP is a service of the American Dental Association to assist dental professionals in identifying quality providers of continuing dental education. ADA CERP does not approve or endorse individual courses or instructors, nor does it imply acceptance of credit hours by boards of dentistry. Dental Learning, LLC designates this activity for 2 CE credits. Dental Learning, LLC is also designated as an Approved PACE Program Provider by the Academy of General Dentistry. The formal continuing education programs of this program provider are accepted by AGD for Fellowship, Mastership, and membership maintenance credit. Approval does not imply acceptance by a state or provincial board of dentistry or AGD endorsement. The current term of approval extends from 2/1/2016 - 1/31/2020. Provider ID: # 346890. Dental Learning, LLC is a Dental Board of California CE provider. The California Provider number is RP5062. This course meets the Dental Board of California’s requirements for 2 units of continuing education. EDUCATIONAL METHODS: This course is a self-instructional journal and web activity. Information shared in this course is based on current information and evidence. REGISTRATION: The cost of this CE course is $29.00 for 2 CE credits. PUBLICATION DATE: March 2017. EXPIRATION DATE: February 2020. REQUIREMENTS FOR SUCCESSFUL COMPLETION: To obtain 2 CE credits for this educational activity, participants must pay the required fee, review the material, complete the course evaluation and obtain a score of at least 70%. AUTHENTICITY STATEMENT: The images in this course have not been altered. SCIENTIFIC INTEGRITY STATEMENT: Information shared in this continuing education activity is developed from clinical research and represents the most current information available from evidence-based dentistry. KNOWN BENEFITS AND LIMITATIONS: Information in this continuing education activity is derived from data and information obtained from the reference section. EDUCATIONAL DISCLAIMER: Completing a single continuing education course does not provide enough information to result in the participant being an expert in the � eld related to the course topic. It is a combination of many educational courses and clinical experience that allows the participant to develop skills and expertise. PROVIDER DISCLOSURE: Dental Learning does not have a leadership position or a commercial interest in any products that are mentioned in this article. No manufacturer or third party has had any input into the development of course content. CE PLANNER DISCLOSURE: The planner of this course, Joe Riley, does not have a leadership or commercial interest in any products or services discussed in this educational activity. He can be reached at [email protected]. TARGET AUDIENCE: This course was written for dentists, dental hygienists, and assistants, from novice to skilled. CANCELLATION/REFUND POLICY: Any participant who is not 100% satis� ed with this course can request a full refund by contacting Dental Learning, LLC in writing or by calling 1-888-724-5230. Please direct all questions pertaining to Dental Learning, LLC or the administration of this course to [email protected]. Go Green, Go Online to www.dentallearning.net to take this course. © 2017

Periodontal disease, including gingivitis, is prevalent in the general population. Periodontal pathogens contained in dental bio� lm play a central role in periodontitis; however, it is the interactions between the host and the bio� lm that in� uence the onset and progression of the disease. Risk factors include environmental, acquired and genetic factors, some of which are modi� able risks. Initial periodontal therapy is typically nonsurgical scaling and root planing, followed by re-evaluation and periodontal maintenance. Antimicrobials may be used adjunctively, including systemic antibiotics, subantimicrobial doxycycline and locally applied antimicrobials. The use of adjuncts, where indicated, is guided by guidelines, and clinical judgment for the individual patient. The overall goal of therapy is to preserve the dentition and maintain or gain clinical attachment, and to prevent disease recurrence.

ABSTRACT

A Review: Bio� lm, the host response and treatment in periodontal disease

Introduction

The 1999 Classi� cation of Periodontal Diseases and Conditions includes 2 main classi� cations: gingival conditions of plaque-induced and

non-plaque-induced origins, and, periodontal diseases/conditions. Periodontitis involves clinical attachment loss (CAL) with loss of alveolar bone together with apical migration of the epithelial attachment. Increased probing depths (PD) and bleeding on probing (BOP) are present. Mild, moderate and severe periodontitis are, respectively, represented by CAL of 1 – 2 mm, 3 – 4 mm, and ≥5 mm.1 A comprehensive update of the current classi� cation is planned for 2017, with the inclusion of risk assessment and prognosis for progression of periodontitis.2

ABOUT THE AUTHOR

Dr. Fiona M. Collins, BDS, MBA, MA Dr. Collins is a national and international speaker and author, and has presented on dental caries, xerostomia, bio� lm, disease prevention, dentifrices, infection control, and tobacco cessation. She has given presentations in North America, Europe, the Paci� c Rim and the Middle East. She has also participated as a faculty member at OSAP Boot Camps. Dr. Collins is a member of the American Dental Association and is the ADA representative to AAMI. She is also a member of the American Association for Dental Research, ADA Standards Committee working groups, the Organization for Safety, Asepsis and Prevention (OSAP), and is a Fellow of the Pierre Fauchard Academy. During her career, Fiona has lived and worked in � ve countries. Dr. Collins graduated as a general dentist from the University of Glasgow in Scotland, and holds an MBA and an MA from Boston University. Dr. Collins is the CE Editor for Dental Learning. She has no commercial interest or relationship with the commercial supporter of this course.

Integrated Media Solutions Inc./DentalLearning.net is an ADA CERP Recognized Provider. ADA CERP is a service of the American Dental Association to assist dental profession-als in identifying quality providers of continuing dental education. ADA CERP does not approve or endorse individual courses or instructors, nor does it imply acceptance of credit hours by boards of dentistry. Concerns or complaints about a CE provider may be directed to the provider or to ADA CERP at www.ada.org/cerp. Integrated Media Solutions Inc./DentalLearning.net designates this activity for 2 continuing education credits.

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Dental Learning, LLC is a Dental Board of California CE Provider. The California Provider # is RP5062. All of the information contained on this certi� cate is truthful and accurate. Completion of this course does not constitute authorization for the attendee to perform any services that he or she is not legally authorized to perform based on his or her license or permit type. This course meets the Dental Board of California’s requirements for 2 units of continuing education. CA course code is 02-5062-17001.

3

PrevalencesBased on the National Health and Nutrition Examination

Survey (NHANES III) of 1988-1994, 50% of adults had gingivitis.3 One study found that 94% of adults had gingivitis (GI ≥0.50),4 and it is estimated that up to 75% of the global population experiences gingivitis.5 Plaque-induced gingivitis is an in� ammatory host response to dental bio� lm.6,7 Early gingivitis is reversible with thorough oral hygiene, while established gingivitis requires professional intervention to treat it. Persistent gingivitis is a risk factor for periodontitis and tooth loss,8 and in a 26-year longitudinal study (n=565; ages 16 to 59), 70% more CAL was observed in subjects approaching age 60 who had long-standing gingivitis vs. subjects with no gingivitis.9 However, the presence of gingivitis does not always lead to periodontitis,10 as shown by the higher prevalence of established gingivitis versus periodontitis in the general population.4,5,11

Periodontitis in adults ≥30 years-of-age was estimated in the 2009-2010 NHANES.11 Based on the de� nitions, 47% of these adults were found to have periodontitis, of whom 8.7%, 30.0%, and 8.5% respectively had mild, moderate, and severe periodontitis.11 Among adults ≥65 years-of-age, an estimated 57% have mild or moderate periodontitis, and 11% have severe periodontitis.12 Occlusal trauma secondary to periodon-titis may exacerbate periodontal destruction.13 Periodontal pathogens are a prerequisite for plaque-induced periodontitis.

Development and Structure of Dental Bio� lmDental bio� lm development begins with pellicle formation at the tooth surface. This is followed by early adhesion and colo-nization by Gram-positive cocci, then by Gram-positive rods and � laments. Next, a shift in the bio� lm occurs with adhe-sion and colonization by Gram-negative bacteria.14 Bacterial production of extracellular lipopolysaccharides (EPS) results in a matrix that binds the bio� lm together and protects microor-ganisms within it.15 Gingivitis can develop in a matter of days once periodontal pathogens are present.16,17 The subgingival

bio� lm matures over a period of several weeks, becoming structured and self-protective, and is most protected deep with-in the bio� lm. The initial host response includes the production of antibodies to bacterial antigens, and the release of cytokines. Vasodilation and the release of polymorphonuclear leukocytes (PMNs), primarily neutrophils, then occur and the PMNs migrate to the in� amed area and enter the tissue along with Immunoglobulin G (IgG).13,18 In established gingivitis, plasma cells, IgG and IgA are present, with little IgM. PMNs are still present and T-cell lymphocytes are most abundant.14,18,19

Plaque HypothesesHistorically, oral bacterial disease was considered to be as-sociated with dental plaque, not with speci� c bacteria. This was followed by the speci� c plaque hypothesis, which holds that speci� c pathogenic bacteria are responsible for disease.20 By the late 1990s, Socransky and Haffajee had identi� ed six bacterial complexes in subgingival dental bio� lms.21 These complexes were color-coded, based on their level of virulence. Bacteria in the yellow, green, purple and blue complexes colo-nize � rst during bio� lm development, while red and orange complex bacteria are the most virulent.14,21,22 Red complex bacteria included Tannerella forsythia (Tf), Porphyromonas

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Adults Older Adults

8.7%

30%

8.5%

11%

Mild Moderate Severe

Figure 1. Prevalence of Periodontitis in Adults12,13

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gingivalis (Pg) and Treponema denticola (Td).21 (Figure 2) The periodontal microbiota has been investigated in

periodontally healthy patients, and in healthy and diseased sites. In young adults with a healthy periodontium,23

periodontal bacteria from interdental samples were assessed by polymerase chain reaction (PCR). For red complex bacteria, Pg was found in 19% of subjects, Tf in 93% and Td in 49% of subjects.23 Based on the analysis, the orange complex was the main one (70.17% on average) followed by the green complex (13.97%). (Figure 3) In addition, the red and orange complexes clustered together, while other complexes correlated with each other but did not cluster.

Dibart et al found that a majority of sites harbored

Streptococcus oralis (So), while in diseased sites greater numbers of Tf, Prevotella intermedia (Pi), Capnocytophaga ochracea (Co) and Campylobacter rectus (Cr) were found.24 In a second study, A. actinomycetemcomitans (Aa), Fusobacterium nucleatum (Fn), Tf, Pg, Pi, and Peptostreptococcus micros (now Parvimonas micra; Pm) were abundantly present in patients with periodontitis.25 In a 2006 study assessing periodontal disease at baseline, after 7 years and a further 8 years later in subjects in Western Java, Aa was found to be a risk predictor for its onset and progression.26

In a study assessing gingival crevicular � uid (GCF) levels of in� ammatory biomarkers, serum IgG and subgingival bacteria, higher levels of red complex bacteria were found at the bio� lm-periodontal tissue interface for patients with deep periodontal lesions and at sites with moderate or high bleeding-on-probing. However, the differences between moderate and high bleeding-on-probing were determined by the overall increased level of bacteria.27 Dental bio� lm is polymicrobial, with differing bacterial concentrations and virulence depending on the location.10,28,29 Additionally, signi� cant differences exist in the prevalence and mix of periodontal pathogens found in periodontal pockets across ethnic groups.30,31,32

The Oral MicrobiomeThe oral microbiome has now been researched,33 with

>1,000 intraoral species identi� ed, many uncultured and unculturable using current methods.34 Up to 100 species are found in individual periodontal pockets,14 with variation in strains within species demonstrating the diversity that may be found within periodontal pockets. More bacteria have been found that are involved in periodontal disease, and it is believed that uncultured/uncultivable microorganisms may include as yet unidenti� ed periodontal pathogens.7 Recent � ndings are discussed later in this article.

Host In� uence on Bio� lmThe ecological plaque theory holds that a state of health

can be maintained provided an equilibrium exists, while changes in the ecology can favor transition to a disease

Figure 3. Average percentage for each microbial complex23

Figure 2. Microorganisms and subgingival bacterial complexes

Tannerella forsythia, Porphyromonas gingivalis, Treponema denticola.

Streptococcus gordoniiStreptococcus intermediusStreptococcus mitisStreptococcus oralisStreptococcus sanguisStreptococcus spp.

E. corrodensC. gingivalisC. suptigenaCapnocytophaga ochraceaC. concisusA. action

V. parvulaA. odontolyticus

Actinomyces species

C. gracilisCampylobacter rectusC. showse E. nodatum Fusobacterium nucleatum F. polymorphum Prevotella intermedia Parvimonas micraP. nigrescensS. constellatus

* Blue complex was <0.01%

13.97% 70.17%

5.17% 8.08%2.61%


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state.35,36 Factors affecting the equilibrium include the local pH, temperature, ‘lifestyle risk factors,’ ethnicity, age, gender and genetics.37 In a state of health, the gingival crevice has a pH just under 7, while a pH of 7.2 to 7.4 and higher (up to around a mean of pH 7.8) occurs in the presence of in� ammation.38 This may encourage preferential growth of periodontal bacteria, including Pg, Pi and Aa.39 Distinct temperature increases are part of periodontal in� ammation and favor Pi, Aa and Pg.

Risk FactorsNumerous individual risk factors exist for periodontal

disease and its progression. In addition, the presence of two/more of bio� lm, tobacco use and alcohol consumption is a strong risk indicator.40 Modi� able environmental risk factors include poor oral hygiene, gingivitis, local factors such as calculus and restoration overhangs,14 and socioeconomic status. Acquired risk factors include tobacco use (modi� able), substance abuse, some systemic diseases and medications (some modi� able). Smoking tobacco is the primary modi� able risk factor for periodontitis.41 Based on NHANES III, smokers have a 4-fold risk and previous smokers a 1.6-fold risk, compared to never-smokers.42 Smoking tobacco has been shown to alter the host response, including collagenase activity.43-45 It is believed that smoking favors periodontal pathogens, including Tf , Pm, Fn and Cr.46 A poorer response to periodontal therapy is observed for smokers, with lower reductions in bacterial load, a greater risk of recurrence and tooth loss.47 A 4-fold risk for periodontitis up to 20 years after prior heavy consumption of alcohol has been observed,48 and higher levels of Fn, Pi, E. corrodens and IL-1ß in alcohol-dependent individuals.49 Use of recreational drugs has also been implicated in risk for periodontitis.50

Diabetes mellitus (DM) is a strong risk factor for periodon-titis,51,52 and inhibits periodontal repair. In one study, severe periodontitis was found in 58% of adults ages 40-69 years with long-duration diabetes vs. 7% without diabetes.53 An association between gestational DM (GDM) and periodontal disease has been found.54 In some studies, higher BOP, mean CAL and PD have been observed in patients with Sjögren’s

syndrome.55,56 Possible mechanisms include changes in cytokine expression and in the levels of antimicrobial agents and other agents.57,58 Dry mouth itself reduces the availability of salivary antimicrobial agents.59 In patients with rheumatoid arthritis (RA), a two-fold risk for periodontitis and a risk for more severe periodontal disease have been found.60,61 Pg plays a role in both diseases, and is present in the synovial � uid of patients with RA.61 The conclusion in one study was that patients with RA would likely bene� t from increased professional care, e.g., scaling and root planing (SRP).61

The role of genetics has been extensively investigated. One factor researched was genes associated with IL-1 produc-tion and the balance of pro- and anti-in� ammatory chemical mediators.62 More recently, the role of epigenetics, whereby chemical alterations to the DNA and proteins (as opposed to encoded genetic changes) result in changes in gene expression, has been researched.63 Stress affects the immune system, can cause increased bacterial growth, is associated with periodon-tal disease and can affect treatment outcomes.64,65 Recent research suggests that obesity may be a risk factor and may alter periodontal in� ammation.66,67

The Host ResponsePeriodontal destruction depends on the balance between

destructive and protective in� ammatory mediators.18,19

TABLE 1. Risk Factors

Poor oral hygiene Gingivitis

Tobacco use Substance abuse

Alcohol consumption Restoration overhangs

Calculus Other local factors

Socioeconomic status Speci� c medications

Diabetes mellitus Obesity

Dry mouth Sjögren's syndrome

Rheumatoid arthritis Stress

Genetics Epigenetics


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Tumor necrosis factor alpha (TNFα), interleukin-1 (IL-1) and IL-6 are reported to be the � rst cytokines to appear.68

IL-1beta and IL-6 stimulate cell migration,69 and TNFαpromotes neutrophil adhesion to blood vessels, aids vascular permeability, and upregulates IL-1beta and IL-6, further promoting cell migration.18 Neutrophil movement and vascular permeability are aided by complement factors, and GCF � ow increases.19 IL-1beta, IL-6 and TNFα are involved in disease progression,18,70 and stimulate production of matrix metalloproteinases (MMPs) involved in bone destruction. The initiation of bone loss also involves toll-like receptor.18,71 Prostaglandins are involved in the disease process, T-lymphocytes secrete receptor activator of nuclear factor kappa-B ligand (RANKL) and RANKL is upregulated by TNFα. In addition, based on GCF samples from patients with CP vs. healthy patients, it has also been suggested that MMP-13 and MMP-9 together can overcome protection by tissue inhibitors of metalloproteinase-1 (TIMP-1).72

Protective factors include transforming growth factor beta (TGF-beta), which downregulates IL-1beta, TNFα and MMPs, helping to prevent tissue destruction. TGF-beta1 levels are inversely related to levels of RANKL in active diseased sites.73

TIMPs inhibit MMPs, and osteoprotegerin inhibits RANKL. IL-4 increases production of TIMPs and osteoprotegerin, may downregulate IL-1 beta, and upregulates IL-10, which in turn downregulates MMPs and RANKL and upregulates TIMPs. IL-10 also inhibits production of interferon gamma, found at high concentrations in severe and progressive periodontitis. IL-10 is believed to limit the severity of periodontitis.18 (Figure 4)

Recent Findings on Dental Bio� lm and PeriodontitisThe keystone pathogen hypothesis holds that speci� c

bacteria present at a very low level may nonetheless direct the bacterial content of bio� lm,74 initiating an in� ammatory response.75

Oral microbiome research, 16S rRNA sequencing and other techniques have made it possible to identify bacteria previously unknown,76 and dental bio� lm is more diverse than previously thought.74 Periodontitis is now considered to be a polymicrobial in� ammatory disease in which the

microorganisms and speci� c strains within dental bio� lm are dysbiotic. This means that their in� uence can result in a change in the bio� lm into one favoring periodontal disease, with increased self-protection and pathogenicity.76,77

In addition, the whole bio� lm community is believed to be associated with periodontal disease.77 Dental bio� lm associated with periodontal disease is considered in� ammophilic, i.e., likes in� ammation, which also means that as in� ammation occurs, the bio� lm shifts further to bacteria that like in� ammation, creating a vicious circle and progressing periodontal disease.78

Bacteria previously considered nonpathogenic are now believed to be involved in periodontal disease, based on the research. Instead of mainly Gram-negative bacteria being as-sociated with periodontal disease and Gram-positive with peri-odontal health, it has been discovered that Gram-positive bac-teria are also involved in this disease. Eubacterium nodatum(En) is found in mature supragingival bio� lm and in bio� lm redeveloped after professional prophylaxis, together with Pg, Tf and Td.79 It is considered possible that Gram-positive bac-teria,80 such as En, Pm and Filifactor alocis (Fa), as well as the bacteria Porphyromonas endodontalis and Prevotella tannerae,may be putative periodontal pathogens. In recent research, Fa, which is Gram-positive, was found to be associated with periodontal disease and to have a high incidence in periodontal pockets, while Veillonella (Gram-negative) was not.81

HostresponseClinicalAttachmentLoss

IL-1,IL-6,TNF-α,MMPs,Cfactors,RANKL,interferongamma

Destructiveinflammatorymediators

Protectiveinflammatorymediators

TIMP-1,TGF-β,Osteoprotegerin,IL-4,IL-10

Figure 4. Destructive and Protective Mediators


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Microorganisms within a mature bio� lm interact and sup-port each other, with various functions within the whole bio-� lm. Commonalities and differences have also been found in the response of periodontal tissues to recognized pathogens.82

The inter-relationship between the host and the microbial en-vironment determines the onset and progression of periodon-tal disease.14 Interaction between different strains of species also occurs, and new bacterial-host interactions likely remain to be discovered.

Microbial and host interactionsIn addition to binding to receptor sites, different species of

bacteria co-aggregate (bind) with each other. Pm mediates co-aggregation with Fn and Pg,83 and co-aggregation of Td and Pg may increase the virulence of both species.84 Gingipains produced by Pg digest host proteins, provide nutrients to other microorganisms and alter the immune response by inhibiting the bactericidal activity of PMNs.85 In addition, gingipains play a role in the co-aggregation of Pg and Pi and may interact with other bacteria.86

In vitro, Fn, Fusobacterium necrophorum, Pe and Pd have been shown to promote MMP release in gingival epithelial cells,18 and Pg may modify the adaptive immune response.87

Multi-species bio� lms have been shown in vitro to elevate levels of interleukins.88 An example of a role for both Gram-positive

and Gram-negative bacteria is the in� uence of Sg in recruiting Pg and other bacteria, and its crucial role in bio� lm formation. Viruses may also play a synergistic role with bacteria, speci� cally human cytomegalovirus and Epstein-Barr virus.77

In vivo, speci� c bacterial combinations in� uence the severity of periodontal disease: Td and Pg levels increase GCF levels of a bone destruction marker;89 and higher IL-8 levels are produced when Aa and Fn are both present.23 In� ammatory mediator levels were also shown to be lower with the com-mensal S. gordoniii (Sg) and higher with periodontal bacteria. Speci� cally, IL-1b levels were higher with Pg, IL-8 with Aa, and Fn resulted in the highest levels of interleukins overall.90

Since many bacteria cannot currently be assessed, it is not known what their in� uence may be on the inter-relationships of bacterial species and the microbial-host relationship.82

Treatment for chronic periodontal disease The goal of periodontal therapy is to halt disease

TABLE 2. Recent Findings on Bio� lm

Bio� lm more diverse than previously thought

Dysbiosis of microorganisms and speci� c strains

Believed whole microbial community involved

Dental bio� lm described as 'in� ammophilic'

Gram-positive bacteria also involved in periodontitis

Fa found to be associated with periodontitis

TABLE 3. Bacterial and Bacterial-Host Interactions

Co-aggregationPm mediates for Fn and PgVirulence of Td and Pg may increase

Gingipains produced by Pg

Digest host proteins, providing nutrients to microorganismsInhibit bactericidal activity of PMNsRole in Pg and Pi co-aggregation

PgMay modify the adaptive immune response

In vitro promotion of MMP release

By F. necrophorum, Fn, Pe, Pd

Gram-positive and Gram-negative

Sg in� uences Pg recruitment

Td and PgIncrease bone destruction marker in vivo

Higher IL-8 levelsWhen Aa and Fn are both present


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progression, to preserve the dentition and maintain or gain clinical attachment, and to prevent disease recurrence.91 Nonsurgical SRP is standard initial therapy for CP, followed by re-evaluation and long-term periodontal maintenance. Clinical judgment is required in determining appropriate treatment and considers the individual patient’s medical and dental history, systemic health, risk factors, preferences, and severity and extent of periodontal disease.92 Levels of Tf, Fn, Pg and Td have been observed to initially decrease signi� cantly after periodontal therapy, and to then slowly increase in the 3rd month onward in pockets with a PD of ≥6 mm.93

In some patients, surgical therapy may be indicated for deep pockets or furcation areas, follow-up in speci� c areas following initial periodontal therapy, or for tissue regeneration. Patients with aggressive periodontitis or moderate to severe chronic periodontitis require more than only scaling and root plan-ing.3 It has also been recommended that a periodontal referral be considered for co-management, evaluation and indicated therapy of these patients and for patients with DM.3 Tobacco cessation should be recommended to users,91 and has been shown to decrease the proportions of Pe, Dialister pneumosin-tes, Pm, Fa and Td.94 The outcome of periodontal therapy de-pends on an individual’s response to treatment, and compliance with appropriate periodontal maintenance and home care.91,95 Depending on the individual patient and clinical judgment, systemic or local adjunctive therapy may be indicated.

Systemic antimicrobialsOptions include, but are not limited to, penicillins, tetra-

cyclines and metronidazole, and combination therapy may be required.96 The adjunctive use of systemic antibiotics is supported by a systematic review � nding their use bene� tted periodontal patients.97 Considerations include the patient’s medical history, microorganisms present, and continuing dis-ease activity. However, antimicrobial resistance is of increasing concern in part related to the use/misuse of systemic antibiot-ics and one of the potential disadvantages of selecting systemic antibiotics. Based on the current ADA EBD guidelines, adjunc-tive systemic antimicrobials may be considered in patients

with moderate to severe chronic periodontitis.98

Subantimicrobial dose doxycycline (SDD)Orally administered SDD (20 mg bid) improves the host

response and outcomes, while not promoting antimicrobial resistance. SDD use for 3 months after SRP resulted in mean PD reductions ≥3 mm in 80% of sites with an initial PD ≥7 mm vs. 51% of sites in patients receiving SRP + placebo in one study (p<0.05).99 SDD has been shown to increase levels of gingival crevicular � uid transforming growth factor-beta1,

and to decrease levels of extracellular MMP inducer in GCF.100

In vitro, in the presence of Aa, SDD inhibits production of TNF-α, IL-1α, IL-1ß, IL-6 and IL-8.101 Based on the current ADA EBD guidelines, the strength of the recommendation is 'in favor' of the adjunctive use of SDD for 3 to 9 months.98

Locally applied antimicrobials (LAAs)LAAs offer controlled, sustained release that keeps

the level of antimicrobial above the minimum inhibitory concentration (MIC), while maintaining low levels systemically.102 Options in the United States include 2% minocycline hydrochloride microspheres (MM; Arestin) and 10% doxycycline hyclate gel (DG; Atridox). DG is applied pre-mixed in a syringe, sets and remains in the site for 7 days, while MM is applied in a syringe as a dry powder that sets in the presence of GCF and remains in the site for 14 to 21 days. In non-smokers, one study found mean PD reductions of 1.99 mm for SRP + MM vs. 0.98 mm for SRP alone at 9 months for pockets with an initial mean PD ≥7 mm following 3-monthly applications.103 In sites with an initial mean PD ≥6 mm, the difference in mean PD reductions was 0.41 mm, favoring SRP + MM (p≤0.01).103 A study with one application of MM found mean PD reductions of 1.3 mm for SRP + MM vs. 0.9 mm for SRP alone (NS).104 Two multi-center trials compared SRP vs. DG as a monotherapy in subjects with moderate to severe CP and ≥4 pockets with an initial PD of ≥5 mm and BOP, 2 of them ≥7 mm. Mean PD reductions in study 1 were 1.1 mm for DG vs. 0.9 mm for SRP (NS).105 In an evaluation of yearly application of DG during initial


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SRP and periodontal maintenance (maintenance itself was 6-monthly), signi� cantly greater reductions in BOP and PD were observed at 3 months only.106

In smokers, adjunctive use of MM for pockets with an initial PD ≥5 mm than SRP alone following treatment at baseline, 6 and 9 months. The mean difference in PD reduc-tions was 0.29 mm (1.19 mm vs 0.90 mm).107 In a short-term study on the gene load of Aa, Fn, Pg and Pi 7 days post-treatment,108 only Pg responded to SRP alone, and only combination therapy signi� cantly reduced the gene load of Pi (p=0.042).108 In patients with moderate to severe CP,109 at 25 weeks, use of MM resulted in more sites with PD reductions of ≥2 and ≥3 mm for smokers. For S only, these reductions were 74% and 32% respectively, and for the S + MM group were 85% (p=0.001) and 45% (p<0.0001), respectively.109

Machion et al assessed the outcome of SRP vs. SRP+DH in smokers with severe CP (n=43) and ≥4 pockets in anterior teeth with BOP and a PD ≥5 mm. Mean PD reductions at 6 months were 1.76 mm for SRP alone and 2.17 mm for SRP + DH (NS). For sites with an initial of PD ≥7 mm, the mean PD reductions were 2.6 mm for SRP alone and 3.78 mm for SRP + DH (p=0.01).110 Patients were retreated at 12 months. At the 2-year follow-up, 65% of sites with an initial PD ≥7 mm treated with DH had a PD reduction ≥2 mm versus 46% in the SRP-only group (p=0.01). Clinical attachment level gains were also superior and occurred at more sites.111

In two multi-center studies comparing smokers, previous smokers and nonsmokers with moderate to severe CP, similar improvements were observed with SRP+DH regardless of tobacco use history, while for the SRP group signi� cant differ-ences in treatment outcomes were observed.112

Based on the current ADA EBD guidelines, the strength of the recommendation is 'expert opinion for' the adjunctive use of minocycline microspheres (Arestin) and doxycycline hyclate (Atridox).98 The decision on whether to use an adjunctive LAA is based on current recommendations and clinical judgment.

ConclusionsPeriodontitis is a multi-factorial disease associated with

the presence of a polymicrobial bacterial bio� lm, and

research points to dysbiosis resulting from a change in the bio� lm or a change in the host response. These changes favor a bio� lm associated with disease and in� ammation. The outcome depends on the host response, including bacterial-host interactions. Given the polymicrobial nature of the bio� lm, one factor in choosing therapies is their effectiveness against a wide range of microorganisms and the severity of disease present. Another is addressing underlying risk factors and the in� ammatory host response. It can be anticipated that new or additional therapies will be discovered in the future that address the in� ammatory and dysbiotic nature of periodontitis. Standard initial therapy consists of nonsurgical SRP. Adjunctive systemic or local therapy may be indicated depending on the clinical circumstances and clinical judgment.98

Improvements in periodontal health rely on the host response and results of active therapy, removal and reduction of modi� able risk factors, thorough home care, and long-term regular periodontal maintenance.

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WebliographySmiley CJ, Tracy SL, Abt E, et al. Evidence-based clinical practice guide-line on the nonsurgical treatment of chronic periodontitis by means of scaling and root planing with or without adjuncts. J Am Dent Assoc. 2015;146(7):525-35. Available at: http://jada.ada.org/article/S0002-8177(15)00334-7/fulltext.


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CEQuizTo complete this quiz online and immediately download your CE veri� cation document, visit www.dentallearning.net/PER-ce, then log into your account (or register to create an account). Upon completion and passing of the exam, you can immediately download your CE veri� cation document. We accept Visa, MasterCard, Discover, and American Express.

1. Mild, moderate and severe periodontitis are, respectively, represented by a CAL of ____________.a. 0–1 mm, 2–3 mm, and ≥3 mmb. 1-2 mm, 3-5 mm, and >5 mmc. 1-2 mm, 3-4 mm, and ≥5 mmd. 1-2 mm, 3-5 mm, and ≥6 mm

2. The prevalence of gingivitis and moderate chronic periodontitis in adults in the US is ____________.a. 30%; 10%b. 40%; 20%c. 50%; 30%d. 60%; 40%

3. Persistent gingivitis always results in periodontitis and tooth loss.a. Trueb. False

4. The oral microbiome has since been investigated and around ____________ intraoral species have been identi� ed, while up to ____________ species have been found in individual periodontal pockets.a. 250; 500b. 500; 750c. 1000; 100d. 1200; 50

5. The speci� c plaque hypothesis holds that ____________ are responsible for disease.a. all intra-oral bacteriab. speci� c pathogenic bacteriac. all microorganismsd. only Gram-positive bacteria

6. Dental bio� lm ____________.a. is polymicrobialb. contains differing concentrations of

bacteriac. varies across ethnic groups, with

different prevalences and mix of periodontal pathogens in periodontal pockets

d. all of the above

7. Tumor necrosis factor alpha (TNFa), interleukin-1 (IL-1) and IL-6 are reported to be ____________ in the in� ammatory cascade.a. protective in� ammatory mediatorsb. the � rst cytokines to appear c. required for osteogenesisd. all of the above

8. It has been suggested that MMP-13 and MMP-9 together can overcome protection by tissue inhibitors of metalloproteinase-1 to inhibit progression of CAL.a. Trueb. False

9. Osteoprotegerin inhibits ____________. a. TIMPsb. MMPsc. Interferon gammad. RANKL

10. ____________ is considered the primary modi� able risk factor for periodontitis.a. Drinking alcoholb. Smoking tobaccoc. The presence of calculusd. Poor oral hygiene

11. Bacteria previously considered nonpathogenic are now believed to be involved in periodontal disease, based on the research. a. Trueb. False

12. In one study, severe periodontitis was found in ____________ of adults 40-69 years-of-age with long-duration diabetes vs. ____________ without diabetes. a. 38%; 5%b. 48%; 6%c. 58%; 7%d. 68%; 8%

13. It was concluded in a recent study that patients with rheumatoid arthritis would likely bene� t from ____________. a. increased professional dental care b. modi� cation of the acquired pelliclec. higher cortisol levelsd. a and b

14. Nonsurgical scaling and root planing (SRP) is standard initial therapy for CP, followed by ____________.a. re-evaluation and long-term periodontal

maintenanceb. re-evaluation and short-term

periodontal maintenancec. re-evaluation and testing for rheumatoid

arthritisd. irrigation and re-evaluation

15. The outcome of periodontal therapy depends on ____________.a. an individual’s response to treatment b. compliance with appropriate

periodontal maintenance c. compliance with home cared. all of the above

16. Gingipains produced by Porphyromonas gingivalis ____________.a. promote the bactericidal activity of

PMNsb. play a role in the co-aggregation of

Porphyromonas gingivalis and Prevotella intermedia

c. inhibit other microorganisms from accessing nutrients

d. result in pain associated with periodontal disease

17. For some bacterial species, their in� uence on the inter-relationships of bacterial species and the microbial-host relationship is not known because ____________.a. they cannot currently be assessedb. the in� uence is likely minimalc. they are less important than othersd. all of the above

18. Orally administered sub-antimicrobial dose doxycycline has been shown to ____________.a. improve the host response and

outcomes b. promote antimicrobial resistancec. increase levels of MMP inducer in

gingival crevicular � uidd. in� uence epigenetics

19. Available locally applied antimicrobials ____________.a. offer sustained release of the

antimicrobial above the minimum inhibitory concentration

b. maintain low levels of the antimicrobial systemically

c. remain at the site for at least a weekd. all of the above

20. Determining what would be appropriate treatment is based on ____________.a. current clinical recommendations and

gut feelb. clinical judgment and patient educationc. current clinical recommendations and

clinical judgmentd. the patient’s age

15

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4. A B C D

5. A B C D

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QUIZ ANSWERSFill in the circle of the appropriate answer that corresponds to the question on previous pages.

EDUCATIONAL OBJECTIVES• Review the role of bio� lm in periodontal disease;• Describe the pathogenesis of periodontal disease, destructive and protective chemical mediators;• List and describe risk factors; and,

• Review options for treating chronic periodontitis and their ef� cacy.

If you have any questions, please email Dental Learning at [email protected] or call 888-724-5230.

COURSE SUBMISSION: 1. Read the entire course.2. Complete this entire answer sheet in

either pen or pencil.3. Mark only one answer for each question.4. Mail or fax answer form. For immediate results:1. Read the entire course.2. Go to www.dentallearning.net/PER-ce.3. Log in to your account or register to create an

account.4. Complete course and submit for grading to

receive your CE veri� cation certi� cate.

A score of 70% will earn your credits.

Dental Learning, LLC500 Craig Road, First FloorManalapan, NJ 07726

*If paying by credit card, please note:Master Card | Visa | AmEx | Discover

*Account Number

______________________________________________

*Expiration Date

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The charge will appear as Dental Learning, LLC.

If paying by check, make check payable to Dental Learning, LLC.

ALL FIELDS MARKED WITH AN ASTERISK (*) ARE REQUIRED

AGD Codes: 490, 495

Price: $29 CE Credits: 2Save time and the environment by taking this course online.

COURSE EVALUATIONPlease evaluate this course using a scale of 3 to 1, where 3 is excellent and 1 is poor.

1. Clarity of objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2 1

2. Usefulness of content . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2 1

3. Bene� t to your clinical practice . . . . . . . . . . . . . . . . . . . . 3 2 1

4. Usefulness of the references . . . . . . . . . . . . . . . . . . . . . . 3 2 1

5. Quality of written presentation . . . . . . . . . . . . . . . . . . . . 3 2 1

6. Quality of illustrations . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 2 1

7. Clarity of quiz questions . . . . . . . . . . . . . . . . . . . . . . . . . 3 2 1

8. Relevance of quiz questions . . . . . . . . . . . . . . . . . . . . . . 3 2 1

9. Rate your overall satisfaction with this course . . . . . . . . 3 2 1

10. Did this lesson achieve its educational objectives? Yes No

11. Are there any other topics you would like to see presented in the future? __________________________________________________________________________

_______________________________________________________________________________________

DENTAL LEARNING

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