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C111SPECIAL CONSIDERATIONS FOR MANAGINGPATIENTS WITH DIABETESMARIA EMANUEL RYAN, DDS, PHDTHURSDAY, FEBRUARY 21

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Treatment strategies combining the use of mechanical therapies and adjunctivechemotherapeutics enable clinicians to better manage periodontal diseases.By Rebecca S. Wilder, RDH, MS, and Maria Emanuel Ryan, DDS, PhD

Oral healthcare professionals continuallyseek ways to address the plaque biofilm andexcessive host response that are responsible

~_-::::; __ ~:::-_ for e-breakdown of connective tissue and bone associated with-~~ =e= While mechanical therapy (such as scaling,root planiQg-and"p,ower instrumentation) is considered the goldstandard ~~fil';ri',disruPtion and removal, the data tell us, '\

~~iOns ~~£I\IE www.dimensionsofdentalhygiene.com

that clinicians rarely if ever achieve complete removal of the

putative pathogens that reside in the biofilm from the surface.'What scientists do know is that the plaque biofilm is composedof a complex group of bacteria living together in a multispeciescommunity. The microbes in the biofilm are stable, and tightlyadhere to each other and to an oral substrate by means of anextracellular matrix.',3 Bacteria in biofilms are much more resist-ant to antimicrobial agents than those dispersed as single cells

of the same species.

Knowing this helps us to understand why antibiotics uti-lized to address the biofilm, either locally applied or systemi-

cally administered, are considered adjuncts to mechanicaltherapy instead of monotherapies. What this means to dentalclinicians is that an optimal therapeutic approach may includeadjunctive therapies such as antiseptics and/or antibiotics, as

well as host modulation (in addition to mechanical therapy) tobest address a complex disease process. Devising a suitable

treatment plan would also depend, of course, on the patient'shost response and oral healthcare habits.

Chemotherapeutic agents are used to eliminate, reduceor alter the effect of microorganisms in the oral cavity and

JUNE 2010

elevated levels of pro-inflammatory media-tors. The term antimicrobial refers to agents

that kill microbes or affect the growth andmultiplication of microorganisms.· Several

chemotherapeutic agents are available to oral

healthcare providers to assist in the control andreduction of supragingival plaque and associ-ated gingivitis. These typically take the form of

mouth rinses or dentifrices. Other agents avail-

able for the control and treatment of chronicperiodontitis, such as locally applied antimicro-bials/antibiotics and systemically administeredantimicrobials, are reserved for more aggres-sive cases.

As noted in Table 1, a valuable quality in

antimicrobial agents is substantiveness, or the

Allare safe when used as directed. Chemother-apeutic dentifrices in the U.S. primarily contain

triclosan or stannous fluoride.

Here is a brief description of the active

ingredients in common chemotherapeutic

mouthrinses and dentifrices used in the con-trol of plaque and gingivitis:

Chlorhexidine (CHX): The antiseptic CHXis one of the most effective antiplaque/antigin-

givitis agents available to clinidans. It is sold inthe U.S. as a prescription mouthrinse at 0.12percent concentration. Most products contain11 .6 percent alcohol, although products with-

out alcohol are also available. The mechanismof action is related to an alteration of bacterialadsorption, a reduction in pellicle formation

A valuable quality in antimicrobial

agents is substantivenessability of an agent to remain in an area or siteand resist being diluted or washed away by gin-gival crevicular fluid or salivary action.' In addi-tion, a systemically administered sub-antimicro-

bial dose of doxycycline (20 mg) has beenapproved by the United States Food and DrugAdministration (FDA) as an adjunctive host

modulatory therapy to reduce levelsof enzymesami cytokines known to drive the breakdown ofonnective tissue and bone metabolism

dTanges associated with periodontitis.

Ol7HRINSES AND;:...;npRICES

rinses designed to reduce plaque andgingivitis contain antiseptic agent:s--<:hemical

antimicrobial agents that are applied topicallyor subgingiva/ly to mucous membranes,wounds or intact dermal surfaces to destroymicroorganisms, inhibit their reproduction orinhibit their metabolism. While most antiseptics

are bactericidal (meaning, killsbacteria), some

are bacteriostatic (that is, they inhibit growth

and reproduction of bacteria without killingthem). The most common active ingredientsin mouth rinses are essential oils of dentifrice:chlorhexidine gluconate (CHX-available byprescription only); cetylpyridinium chloride(CPC) and stannous fluoride. These agents

have been evaluated in the laboratory (pre-clin-

ically)and in clinical trials for efficacy and safety.

JUNE 2010

and an alteration of the bacterial cell wall caus-ing lysisto occur. A major advantage of CHX isthat it is a very substantive agent that brings

reductions in plaque biofilm and gingivitis

ranging from 22 to 61 % and 18 to 44%,respectively," The disadvantages of CHX are

teeth staining, alteration of taste and anincrease in calcified deposits.

Essential Oils: The three essential oils are amixture of thymol, menthol and eucalyptolcombined with methyl salicylate. The alcohol

content is 21.0 to 26.9%. The mechanism ofaction is related to alteration of the bacterial

cell wall. Studies have reported plaque and gin-givitis reductions ranging from 14 to 56% and14 to 39%, respectively," The adverse effect is abuming sensation during use with certain for-mulations.

Cetylpyridinium Chloride (CPC): CPC is

classified as a quaternary ammonium com-pound. The mechanisms of action include: rup-

ture of cell walls; the promotion of cell lysis;

decreased cell metabolism; and the ability for

bacteria to attach to tooth surfaces. Studieshave reported plaque and gingivitis reductionsof 15% and 24%, respectively!-· Reported sideeffects include staining, increased calculus for-mation and occasional buming.

Stannous Fluoride (SnF2): SnF2 products

are available in rinses and dentifrices. Formula-

tions vary from 0.63% in rinses to 0.045% in

dentifrices. Previous reports showed a reduc-tion in plaque biofilm and gingivitis for shortperiods after use. A possible downside is that

formulations have received mixed reviews in

the past due to the instability of stannous fluo-

ride (although new, more stable formulationsare available). Reported side effects includestaining and altered taste.

Triclosan: This is a broad spectrum anti-

bacterial agent. In the U.S., triclosan (0.03%)is only available in a dentifrice with thecopolymer Gantrez (2.0%), which improvesits efficacy. With the addition of 0.243 sodiumfluoride in a silica base, it has demonstrated

efficacy in reducing plaque, gingivitis calculusand dental caries.' Reductions in plaque andgingivitis ranging from 12 to 59% and 22 to

250/0, respectively, have been reported.'? Tri-closan has been used safely for many years.

CHEMOTHERAPEUTIC AGENTSFOR CHRONIC PERIODONTITISAlthough many patients will respond tothorough debridement and self-care thera-

pies such as described above, for patients

who do not improve or for whom their peri-odontal health continues to decline,stronger adjunctive therapies may be neces-

sary. Since the 1980s, locally applied antimi-crobials/antibiotics (lAAs) have been avail-able to dental professionals. (See Table 2.)

Currently, three resorbable, site-specific

locally administered antimicrobial/antibi-

otics products approved by the FDA for thetreatment of chronic periodontitis areavailable. They are: Arestin" (OraPharma,Inc. Warminster, Penn.), minocydine micros-pheres; AtridoxTM (Tolrnar Inc. Ft. Collins,Colo.), a doxycycline gel; and PerioChip'"

(Dexcel Pharma, Alzenau, Germany), a

chlorhexidine based chip. PerioChip is the

www.dimensionsofdentalhygiene.com Dimensions OF DENTAL HYGIENE 45

w

Chemotherapeutics

only antiseptic LAA; it is not an antibiotic.

Patients who have an allergy to the tetracy-

cline class of drugs or who are pregnant

should have PerioChip placed if an LAA is

indicated.

These agents, used as an adjunct to scaling

and root planing, deliver an antiseptic or antibi-

otic to the base of the periodontal pocket with

the goal of improving pocket depth reductions,

clinical attachment level gains and reductions

in bleeding on probing. The substantivity of

the agents vary (seven days for chlorhexidine

glucontate" and doxycycline;" 14 to 21 days

for minocycllne'"). However, all have greater

substantivity than mouth rinses used subgingi-

vally as irrigants. The added benefit of the

agents is the slow release of the active ingredi-

ents at a higher minimal inhibitory concentra-

tion (MIC) level than can be achieved by any

other application. The MIC represents the con-

centration of antibiotic required to inhibit

growth of a planktonic bacterial population.

Locally delivered, site-specific agents have a

higher and longer substantivity and maintain

MIC long enough to significantly reduce the

level of pathogens, leading to improvements

in the periodontal condition after single or mul-

tiple applications.

While all of the agents were studied in

nine-month clinical trials for the improvement

of chronic periodontitis, more recent investi-

gations continue to show benefits for high-

risk patients. For example, Goodson et al

demonstrated that Arestin ™ significantly

reduces periodontal pathogens comprising the

"red complex" (i.e., P gingivalis, T. forsythia and

T. denticola), compared to scaling and root

planing alone by one month, particularly in

smokers." A two-year follow-up of Atridox™

and scaling and root planing in smokers

demonstrated sustained improvements in

probing depth reductions and relative attach-

ment level gains beyond what was achieved

with scaling and root planing alone." These

findings are important for clinicians who strive

to improve the periodontal condition of

patients who do not respond to mechanical

therapy. Recent studies have demonstrated

the intensive periodontal therapy with locally

applied antimicrobials also results in significant

reduction in the overall inflammatory burden,

with reduced risk for cardiovascular events.'6.17

OTHER WCALLY APPLIEDPRODUCTSPeriowaveTM (Periowave Dental Technologies,

Ine. Toronto, Ontario, Canada), currently not

approved for use in the U.S., is a non-antibi-

otic therapy intended to destroy gram nega-

tive bacteria without promoting the devel-

opment of bacterial resistance." Used in the

treatment of chronic periodontitis, it utilizes

a cold (non-thermal), low-power diode laser

as the activating light. Indications for use are

for patients with 4 to 9 mm pockets that

bleed on probing.

Marketed as a method to treat chronic peri-

odontitis, Perio Protect" (Perio Protect LLC, SL

Louis, Mo.) relies on a custom-made tray to

deliver a solution (selected by the dentist) to

chemically alter the biofilm in the periodontal

pocket and change the pocket's microbiologi-

cal environment to disrupt biofilm growth. In

November 2009, the American Academy of

Periodontology (AAP) published a fact sheet on

its consumer website to educate the public

about Perio Protect.'? The AAP reported that it

was not aware of any randomized, controlled

clinical trials published in peer-reviewed sclen-

Product !\fame! . Active Method of Delivery Mechanism of Action IndicationsManufacturer Ingredient Contra indications

ARESTIN· Minocycline Loc;ally delivered Contains the antibiotic minocycline, a As an adjunctive therapy to seal- Should not be'(minocycline Hel microspheres pack- member of the tetracycline class of ing and root planing procedures used on patientsHCI1mg) aged in a specially antibiotics; minocydine exerts its for reduction of pocket depth with known sen-Microspheres designee unit-dose antimicrobial activity by inhibiting pro- and bleeding on probing in sitivitv to

cartridge, which is tein synthesis and has been shown to patients with adult periodontitis minocycline or

OraPharma inserted into a car- be effective against the pathogens tetracyclines, in

Inc tridge handle to associated with periodontal disease children, or inadminister the prod- pregnant oruet into the pocket nursing women,Single patient use; Subgingival controlled-release product For use in the treatment of Should not besyringe suspended composed of a two-syringe mixing sys- chronic adult periodontitis for used in patientsin 450 mg of tern; one syringe contains 450 mg of the a gain in clinical attachment, who are hyper- ..ATRIGEL* [poly(DL- ATRIGEL delivery system, which is a bioab- reduction in probing depth, sensitive toLactide):NMP] sorbable, flowable polymeric formulation and reduction in bleeding on doxycycline or

composed of 36.7"10 poly(DL-lactide) dis- probing any other drugsolved in 633% N-methyl-2-pyrrolidone; in the tetracy-the second syringe contains doxycycline cline classhyclate, which is equivalent to 42.5 mg of ~~V·~

doxycycline; the constituted product is apale yellow to yellow viscous liquid with acom:entration of 10% of doxycyclinehvdate: upon contact with the crevicularfluid, the liquid product solidifies andthen allows for controlled release of thedrug for a period of seven days

Chlorhexi- Gelatin chip; no spe- Bactericidal: the chlorhexidine mole- Adjunctive to scaling~ and root Should not'be~

dine glu- dal instrument is cule reacts with the microbial cell sur- planing procedures for reduction used in anyManufactured conate needed for insertion; face, destroys the integrity of the cell of pocket depth in patients with patient whoby Dexcel (2.5 mg) standard cotton for- membrane, penetrates in the cell, adult periodontitis; PerioChip has a knownPharrna, Dis- ceps are suggested; precipitates the cytoplasm, and the may be used as part of a peri- sensitivity totributed by tissue should be cell dies odontal maintenance program, chlorhexidineMIS Implants driea before the (hip which includes good oral hygieneTechnologies is inserted and scaling and root planing

46 Dimensions OF DENTAL HYGIENE www.dimensionsofdentalhygiene.com JUNE 2010

Chemotherapeutics

tiftc journals on the efficacy of this therapy. FDAapproval relative to this product is for the tray

as a device only.

In the 1980s it was recognized that al-

though bacteria may initiate the periodontaldisease process, they were insufficient by them-selves to cause peridontitis. Research supported

the fact that a person's response to the perio-

dontal pathogens, known as the host response,was key to the development and progression of

the disease. Elevations in pro-inflammatorymediators (such as cytokines, prostanoids and

enzymes known as matrix metalloproteinases)

were driving the disease process, leading to theconnective tissue breakdown and bone metab-olism changes patho-gnomonic of periodonti-

tis. These findings resulted in the developmentof an FDA-approved host modulatory therapyknown as Periostat. This therapy evolved as anew use for an old drug, doxycycline, whichwhen used at a sub-antimicrobial dose (20mg)could inhibit the destructive enzymes andreduce the excessive levels of cytokines associ-ated with active disease.

When administered at this sub-antimicro-bial dose, doxycycline does not cause thelong-term side effects seen with high doses

of antibiotics such as gastrointestinal upset,the overgrowth of yeast and the de-velopment of bacterial resistance. Periostatwas tested in multiple randomized double

blind placebo controlled clinical trials andfound to be an effective adjunct to scaiingand root planing, contributing to significantimprovements in probing depth reductions,clinical attachment level gains, and reduc-tions in bleeding on probing with no adverseeffects.2o It has been shown to boost theeffects of locally applied antimicrobials suchas Atridox." Recent clinical studies have sup-

ported its use in high-risk patients who are

more difficult to manage, such as smokers,"people with diabetes-> and women withosteoporosis/ osteopenia, 24 as well as thoseat risk for cardiovascular disease.2S It is avail-able in a generic form by prescription onlyand should be used for a minimum of threemonths.

CONCLUSIONDental professionals have come a long way indeveloping strategies that help in the preven-

tion and treatment of periodontitis. Treatmentstrategies combining the use of mechanicaltherapies and adjunctive chemotherapeutics

enable us to better manage both gingivitis and

periodontitis. The use of antiseptics, antibioticsand host modulatory therapy as adjuncts to

brushing, ultrasonics, scaling and root planinghave made non-surgical therapies more pre-dictable, resulting in improvements in plaquecontrol, pocket depth reductions, clinical

attachment levels and bleeding.The implementation of intensive periodon-

tal therapy may not only improve the oral con-

dition of patients, but may also have a positiveimpact on their overall health. Re-evaluationand constant monitoring of patients is essential

when managing a chronic progressive disease,

and clinicians must recognize that when non-surgical therapy is not enough, they must con-

sider surgical approaches to manage periodontaldiseases. We are fortunate to be practicing inan era where we have the tools to treat a widearray of patients with varying riskfor the devel-opment and progression of peridontitis. It is upto us to plan treatment strategies that addressthe unique needs of each patient e

REFERENCES1. KepicTj,O'leary TJ,KafrawyAH.Total calculus removal: an attainable objective? Periodontol. 1990;61:16-20.2. Ustgarten MAStructure of the microbial flora associated with periodontal health and diseases in m~·n.} Periodontol. 1976;47:1-18. .1N '

3. Cobb CM,KilloyWj.Microbialcolonization in human periodontal disease: an illustrated tutorial onselected ultrastructural and ecologicconsiderations. Scan Microsc. 1990;4:675-691.4. American Academy of Periodontology:AAPguidelines for periodontal therapy.} Periodontol.2001;72:1624-1628.5. E1wortbyA,Greenman J, Doherty FMet al. 'Thesubstantivity of a number of oral hygiene productsdetermined by the duration of effectson salivarybacteria.} Periodontal. 1996;76;572-'576.6. Addy M.Chlorhexidinecornpared with other locallydelivered antimicrobials.j Gin Periodontol.1986;13:957-964. "7. t.obene RR.Lobene S,Soparkar PM.The effect of a cetylpyridiniumchloride mouthwash on plaqueand gingivitis.}Dent Res. 1977;56:595.8. AllenDR,DaviesR,Bradshaw B et al. Efficacy'of a mouth rinse containing 0.05%cetylpyridiniumchloride for the control of plaque and gingivitis:a six-month study in adults. Compend Contin Educ Dent1998;19:20·26.9. VolpeAR.Petrone ME,DeVizioWet al. A reviewof plaque, -gingiVitis,calculus and caries clinicalefficacywith a dentifrice containingtriclosan and PVM/MACopolymer.}Clin Dent 1993;4:31-41.10. CubellsAB,Dalrnau LB,Petrone MEet al. The effect of a tritlosan111opolymer/flu0ridedentifrice on,plaque formation and gingivitis:a six-month study.} Gin Dent 1991;2:63-69.11. Jeffcoat MK,BrayKS,CiancioSGet al. Adjunctiveuse of a a subgingivalcontrolled-releasechlorhexidine chip reduces probing depth and improves attachment level compared with scalingandroot planing along.} PeriodontoI1998;69:989-997.12 StollerNH,johnson LR,Trapnell S et al. The pharrnacokinetic profileof a biodegradable controlledrelease deliverysystem containing doxycyclinecompared to ~emically delivered doxycyclinein gingivalcrevicularfluid, saliva,and serum.} Periodontal. 1998;69:1085-91. -13. ChristerssonLA. TISSUeresponse and release of minocyclineafter subgingivaldeposition by use of aresorbable polymer.Warminster,Pa: OraPharma Ine;1988.14. Goodson jM, GunsolleyjC,GrossiSGet al, MinocyclineHCImicrospheres reduce red-complex bacteriain periodontal disease therapv j Periodontol. 2007;78:1568-79. .15. Machion L, Andia DC, Leeio Get al, locally delivered doxvcvclineas an adjunctive therapy to SEalingand root planing in the 'treatment of smokers: a two-year follow-up.}Periodontol. 2006 Apr,77(4):606-13.16. O'AiutoF, Parkar M,NibaliLet al. Periodontal infectionscause changes in traditional and novelcardiovascular riskfactors: results from a randomized controlled clinicaltrial.Am Heart j. 2006 May;151(5):977-84.17. Tonetti MS,D'Aiuto1",NibaliLet al. Treatm~nt of periodontitis and endothelial function. N Engl} Med.2007 Mar 1;356(9):911-20.18. http://www.periO\vave.com.AccessedApriI16.2010.19. http://www.perioprotectcorn/whatls.asp. AccessedApril16,2010 ..20. CiancioS,AshleyR.Safetyand efficacyof sub-antimicrobial-dosedoxycyclinetherapy in patients withadult periodontitis.Adv. Dent Res. 1998 NOV;12(2):27-31.21. Novak MJ,Dawson DR3rd, Magnusson Iet al. Combining host modulatiori and topical antimicroBialtherapy in the management of moderate to severe periodontitis: a randomized multicenter trial.} Periodontol. 2008jan;79(1):3341.22 Preshaw PM,HeftiAF,Bradshaw MHet at. Adjunctivesubantimicrobial dose doxycyclinein smokersand non-smokers with chronic periodontitis.} Gin Periodontol. 2005 jun;32(6):61<F6.23. Martorellide LimaAF,CUryCCet al. Jherapy with adjunctive doxyt;:Yclinelocal deliverv in patients withtype 1 diabetes mellitus and periodontitis.} Gin Periodontol. 2004 Aug;31(8):648-53.24. Reinhardt RA,Stoner JA,Golub LMet al. Efficac;yof sub-antimicrobial dose doxycyclinein post-menopausal women: clinicaloutcomes.] Gin Periodontol. 2007 Sep;34(9):768-75.29. Brown Dl, Desai KK, VakiliSA.El(II. Oinicaland BiochemicalResultsof the MetalloproteinaseInhibitionwith Subantimicrobial Doses of 00xycydine to Prevent AcuteCoronarySvndromes (MIDAS)PilotTrial.Afterioscfer Thromb Va¥, ~iol. 2004;24:733·738.

48 Dimensions OF DENTAL HYGIENE www.dimensionsotdentalhygiene.com JUNE 2010

Nonsurgical Approaches for theTreatment of Periodontal Diseases

Maria Emanuel Ryan, DDS, PhDDepartment of Oral Biology and Pathology, School of Dental Medicine,

Stony Brook University, State University of New York,

South Campus, Stony Brook, NY 11794-8702, USA

Periodontal diseases are the most common dental conditions. Gingivitisis gingival inflammation associated with plaque and calculus accumulation.Gingivitis may or may not progress to more advanced forms of the diseaseknown as periodontitis, which is associated with alveolar bone loss anddiagnosed by increases in probing depths, loss of clinical attachment, andradiographic evidence of bone loss. Periodontitis is chronic and progressiveand there is no known cure. Periodontal disease, however, is treatable andmay even be prevented. Risk for periodontal disease and lack of treatmentof periodontitis have been linked to the systemic health of the patient.Periodontitis is a complex interaction between an infection and a susceptiblehost.

Periodontal disease is initiated by an infection; however, it appears tobehave not like a classic infection but more like an opportunistic infection.As a biofilm-mediated disease, periodontal disease is inherently difficult totreat. One of the greatest challenges in treatment arises from the fact thatthere is no way to eliminate bacteria from the oral cavity, so bacteria willalways be present in the periodontal milieu. In addition, the bacteria withinthe biofilm are more resistant to antimicrobial agents and variouscomponents of the host response. When certain, more virulent species existin an environment that allows them to be present in greater proportions,there is the opportunity for periodontal destruction to occur. Although it isapparent that plaque is essential for the development of the disease, the

The author is a consultant, serves on a number of advisory boards, and is named on pa-

tents as an inventor of therapeutic applications of tetracyclines discussed in this article.

These patents have been fully assigned to the research foundation of Stony Brook

University, State University of New York, Stony Brook, New York, and have been licensed

exclusively to CollaGenex Pharmaceuticals, Newtown, Pennsylvania.

E-mail address: maria.ryan@stonybrook.edu

0011-8532/05/$ - see front matter � 2005 Elsevier Inc. All rights reserved.

doi:10.1016/j.cden.2005.03.010 dental.theclinics.com

Dent Clin N Am 49 (2005) 611–636

severity and pattern of the disease are not explained solely by the amount ofplaque present.

In the 1980s, research began to focus on the relationship between thebacteria in the oral cavity and the response of the individual challenged bythese bacteria or the bacterial host [1]. As a result of multiple studies, it wasrecognized that although there is evidence that specific bacterial pathogensinitiate the pathogenesis of periodontal disease, the host response to thesepathogens is equally if not more important in mediating connective tissuebreakdown including bone loss. It has become clear that certain host-derived enzymes known as the matrix metalloproteinases (MMPs) andchanges in bone resorptive osteoclast cell activity driven by factors known ascytokines and other inflammatory mediators such as prostanoids cause mostof the tissue destruction in the periodontium (Fig. 1) [2].

Risk factors

It has been recognized that the severity of periodontal disease, its rate ofprogression, and its response to therapy vary from patient to patient.Bacteria are essential for the initiation of the disease but insufficient bythemselves to cause the disease. The host must be susceptible, and it is thepatient’s risk factors that determine susceptibility to the disease. Risk factorsare patient characteristics associated with the development of a disease.

Antigens

LPS

OtherVirulenceFactors

PMNs

Antibody

Genetic Risk Factors

Environmental & AcquiredRisk Factors

Cytokines

Prostanoids

MMPs

HostImmune-

InflammatoryResponse

Connectivetissue and

bonemetabolism

Clinical signs ofdisease

Microbialchallenge

Tissue breakdown products and ecological changes

Fig. 1. The pathogenesis of periodontitis. LPS, lipopolysaccharide; PMNs, polymorphonuclear

neutrophils. (Adapted from Page RC, Kornman KS. The pathogenesis of human periodontitis:

an introduction. Periodontol 2000 1997;14:10; with permission.)

612 RYAN

Risk assessment in the patient with periodontitis

There are a number of environmental and acquired risk factors that playa major role in the host response and can increase a patient’s susceptibilityto periodontitis. Listed in Box 1 [3–5] are the risk factors that should be

Box 1. Risk assessment for periodontitis

1. Heredity as determined by genetic testing and familyhistory

2. Smoking including frequency, current use, and history3. Hormonal variations such as those seen in

a. pregnancy in which there are increased levels ofestradiol and progesterone that may change theenvironment and permit the virulent organisms tobecome more destructive

b. menopause in which the reductions in estrogen levelslead to osteopenia and eventually osteoporosis

4. Systemic diseases such asa. diabetes (the duration and level of control are

important)b. osteoporosisc. immune system disorders such as HIVd. hematologic disorders such as neutropeniase. connective tissue disorders such as Marfan’s

and Ehlers-Danlos syndromes5. Stress as reported by the patient6. Nutritional deficiencies that may require a dietary analysis7. Medications such as

a. calcium channel blockersb. immunomodulatory agentsc. anticonvulsantsd. those known to cause dry mouth or xerostomia

8. Faulty dentistry such as overhangs and subgingivalmargins

9. Excessive occlusal loads10. Poor oral hygiene resulting in excessive plaque and

calculus11. History of periodontal disease12. Additional risk factors including hyperlipidemia and possibly

arthritis

Data from Refs. [3–5].

613NONSURGICAL APPROACHES

assessed because they can affect the onset, rate of progression, and severityof periodontal disease and response to therapy.

It is important to document and determine the patient’s risk and toconvey to the patient that these risk factors can be more than additive. Thevalue of risk assessment is that it can help the practitioner to establish anaccurate diagnosis, provide an optimal treatment plan, and determineappropriate maintenance programs. Risk assessment may help to explainvariability in treatment responses. In patients with multiple risk factors, thepractitioner may proceed with caution with regard to invasive surgicalprocedures and may aggressively use pharmacologic adjuncts such asantimicrobials and host modulatory therapy in addition to mechanicaltherapy. When considering a risk-based approach to therapy, there is lesswatching and waiting to see what will happen and more frequent activetreatment and maintenance therapy. It is also important to note that riskassessment is an ongoing process because a patient’s risk changesthroughout his or her life.

Risk modification

Some of these risk factors can be modified to reduce a patient’ssusceptibility to periodontitis. In addition to more frequent dental visits,including active treatment andmaintenance visits, risk reduction may includethe strategies listed in Box 2. The field of ‘‘perioceutics,’’ or the use ofpharmacologic agents specifically developed to better manage periodontitis,is emerging to aid in the management of susceptible patients who developperiodontal disease. When patients are unable to effectively reduceriskdsuch as the risk presented by the patient’s genetics, smokers who areunable to kick the habit, patients who are unable to maintain adequate oralhygiene, the inability to reduce stress, diabetics who are poorly controlleddespite the physician’s best efforts, and the inability or unwillingness of thephysician to alter medicationsdpatients may require the use of perioceutics.Perioceutics includes antimicrobial therapies that can be used to addresschanges in the microflora and host modulatory therapy that can be used toaddress a host response consisting of excessive levels of enzymes, cytokines,and prostanoids and excessive osteoclast function that may be related tocertain risk factors.

The antimicrobial approach

The antimicrobial approach to periodontal therapy has been used formany years, recognizing that the prevalence and severity of these diseasescan be reduced by mechanical plaque removal or by the use of a variety ofsystemic or topically applied antimicrobial agents aimed at inhibitingpathogenic bacteria.

614 RYAN

Mechanical therapy

Brushing and flossing, as part of an oral hygiene routine, is the first-lineapproach to microbial reduction. The American Dental Association (ADA)recommends brushing for 2 minutes twice a day and flossing once a day.Many patients also use interproximal brushes, stimudents, and othermechanical aids to reduce plaque levels. Proper oral hygiene can effectivelyreduce gingivitis and aid in the treatment of periodontitis. Oral hygieneinstructions should be given to all patients undergoing periodontal therapy.The unfortunate reality is that despite clinicians’ best efforts, many patients

Box 2. Risk reduction strategies

1. More frequent visits for those with a genetic predispositionand the use of perioceutics (use of pharmacotherapeuticsfor the management of periodontitis)

2. Smoking cessation using one or more of the six approvedregimens; these regimens rarely are successful as soletherapies (multiple forms of therapy often are used incombination with counseling to achieve success)

3. Hormonal variations such as those seen ina. pregnancy require good oral care before pregnancy

to prevent complications during pregnancy; treatmentof women during pregnancy may be necessary toprevent adverse pregnancy outcomes

b. menopause may require hormonal supplements,calcium, and other medications and supplementsprescribed by the physician to prevent osteopenia

4. Systemic diseases that require consultation with thephysician include

a. diabetes (for improved glycemic control)b. osteoporosis (requiring calcium supplements,

bisphosphonates)c. immune system and hematologic disordersd. connective tissue disorders

5. Stress management; possible referral to a psychologist orpsychiatrist

6. Nutritional supplementation; possible referral to anutritionist

7. Medications can be changed in consultation with thephysician

8. Corrective dentistry9. Occlusal adjustments

10. Improved oral hygiene

615NONSURGICAL APPROACHES

do not spend a sufficient amount of time brushing andmost cannot or will notfloss on a daily basis [6]. These circumstances result in a population in whichmore than 50% of adults have gingivitis [7]. Studies have demonstrated thatpowered toothbrushes, particularly those that work with rotation oscillationaction, are safe and often more effective than manual toothbrushes atreducing plaque and gingivitis in the long- and short-term [8]. Poweredbrushes with timers help patients to comply with the recommended30 seconds per quadrant of toothbrushing twice a day. Despite attempts toencourage plaque removal solely by mechanical means, adjuncts to existinghome care routines have been developed to aid in the removal of plaque.

Tooth scaling by the dental care provider is also a key component intreating and preventing gingivitis. Aggressive subgingival debridementincludes scaling and root planing (SRP) by manual instrumentation orwith sonic or ultrasonic scalers. SRP has become the ‘‘gold standard’’nonsurgical treatment of periodontitis, with multiple clinical studiesdemonstrating that it effectively reduces the microbial load and leads toreductions in bleeding on probing and probing depths and allows for gainsin clinical attachment. A review of nonsurgical mechanical pocket therapyby Cobb [9] reveals mean probing depth reductions and clinical attachmentlevel gains of 1.29 mm and 0.55 mm, respectively, for initial probing depthsof 4 to 6 mm before treatment and 2.16 mm and 1.19 mm, respectively, forinitial probing depths of O6 mm before treatment. Conventional non-surgical periodontal therapy involves performing SRP in single or multiplequadrants or sextants per visit and is usually completed in 2 to 6 weeks. Thenew concept of full-mouth disinfection for the prevention of reinfectionfrom bacterial reservoirs has recently been introduced and shows promisingresults but requires further investigation [10]. In addition, the use of laserswithin the periodontal pocket is being investigated and may emerge as a newtechnical modality for nonsurgical therapy in the near future [11].

Mechanical removal of plaque and calculus (nonsurgical and withsurgical access) is time-consuming, operator and patient dependent, anddifficult to master [12]. Although mechanical and surgical interventionscontinue to be the most widely used methods of controlling diseaseprogression, instrumentation inevitably leaves behind significant numbers ofmicroorganisms, including putative pathogens. Recolonization of thesepathogens can occur within 60 days of SRP, resulting in the need for regularmaintenance visits. The need for chemotherapeutic agents as adjuncts tomechanical and surgical debridement is compelling.

Antiseptics

Antiseptics can be used topically or subgingivally. They are agents thatkill oral microorganisms that cause gingivitis, periodontitis, and caries.Antiseptics are not antibiotics or disinfectants and do not cause bacterialresistance.

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Rinses and irrigationAntiseptic mouthrinses have been used to aid in controlling plaque build-

up. They have been used to complement, not replace mechanical therapy.Two clinically proven ADA-accepted antiseptic mouthrinses are Peridex(Zila, Inc., Phoenix, Arizona; chlorhexidine gluconate) and ListerineAntiseptic Mouthrinse (four essential oils; Pfizer, Inc., Morris Plains, NewJersey), studied in clinical trials of at least 6 months’ duration. Both of theserinses have demonstrated an extremely broad spectrum of kill in vitro andin vivo. In a number of randomized, double-blinded, controlled 6-monthclinical studies, these two agents demonstrated comparable efficacy forimproving reductions in plaque and gingivitis compared with brushing alone[13,14]. Clinical studies have demonstrated additional benefits with the useof these antiseptic mouthrinses, such as control of oral malodor [15,16],enhancement of the benefits of oral irrigation [17,18], improvement in thegingival health around dental implants [19], reductions in plaque andgingivitis in orthodontic patients [20], reductions in bacteria in saliva anddental aerosols when used preprocedurally [21], and support of early healingafter gingival flap surgery [22,23].

Chlorhexidine gluconate. Chlorhexidine gluconate is available at 0.12% inthe United States and has strong substantivity [24]. Chlorhexidine isavailable only by prescription and is partly to fully covered by someprescription plans. Chorhexidine can stain teeth, the tongue, and aestheticrestorations. It can promote supragingival calculus formation and may altertaste perception [25]. When prescribed, it is recommended that patients rinsetwice a day for 30 seconds with 15 mL after brushing and flossing and aftertoothpaste has been completely rinsed out of the mouth.

Listerine. Listerine is available over-the-counter and is composed of a fixedcombination of essential oils: thymol (0.064%), eucalyptol (0.092%), methylsalicylate (0.060%), and menthol (0.042%). Some patients complain of atransient tingling sensation. Listerine’s comparable efficacy in reducinginterproximal plaque and gingivitis to the ‘‘gold standard’’ of flossing wasdemonstrated in a recent study in which 611 subjects rinsed twice daily orflossed once daily as an adjunct to brushing for 6 months [26,27]. In addition,the incremental benefit (with regard to plaque and gingivitis reduction) ofListerine in patients who were already brushing and flossing was demon-strated in a brush, floss, and rinse study [28]. The recommendation for use isrinse twice a day for 30 seconds with 20 mL after brushing and flossing.

ToothpasteTriclosan. Triclosan is present in a toothpaste (Colgate Total; ColgatePalmolive, Piscataway, New Jersey) currently available in the United States.Triclosan is a substantive antibacterial agent that adheres to the oral mucosa,hard, and soft tissues for up to 12 hours. Colgate Total is approved by the

617NONSURGICAL APPROACHES

Food and Drug Administration (FDA) and accepted by the ADA fortreatment of gingivitis, plaque, caries, calculus, and oral malodor. Placebo-controlled studies in smokers [29] and in subjects with recurrent periodontitis[30] suggest that an oral hygiene regimen including a triclosan/copolymerdentrifice may sustain the short-term effect of nonsurgical therapy in smokersand improve on healing after nonsurgical treatment of recurrent peri-odontitis as measured by improvements in gingival inflammation, probingdepths, and probing attachment levels. Triclosan in vitro has anti-inflammatory effects, inhibiting cytokine-stimulated (interleukin 1b andtumor necrosis factor a) production of prostanoids (prostaglandin E2) frommonocytes, reducing the activity of the enzyme cyclooxygenase 2 responsiblefor the production of prostanoids in culture, and inhibiting bone resorptionin a parathyroid hormone–induced release of calcium from bone cultures[31].

Locally applied antisepticPeriochip. Periochip (Dexcel Pharmaceuticals, Israel) is an orange-brown,biodegradable, rectangular chip rounded at one end that has an activeingredient of chlorhexidine gluconate (2.5 mg) that is released into thepocket over a period of 7 to 10 days. It has been found to suppress thepocket flora for up to 11 weeks post application [32]. In a 9-monthrandomized, blinded, and controlled parallel arm study, Periochip, as anadjunct to SRP, significantly reduced probing depths and maintainedclinical attachment levels relative to baseline at 9 months compared withcontrols with repeated application of the Periochip up to three applicationsper site over 9 months [33]. Periochip effects on alveolar bone weredemonstrated in a 9-month randomized, blinded, and placebo-controlledstudy. After 9 months of adjunctive treatment with Periochip, no sitesexhibited bone loss and 25% of the sites experienced bone gain as measuredthrough subtraction radiography [34]. In contrast, 15% of periodontal sitestreated with SRP alone experienced bone loss. Periochip has a documentedsafety profile and does not cause any visible staining. The most frequentlyobserved adverse event in the clinical trials was mild to moderate toothache,which often resolved spontaneously and required no further treatment. Thisadverse event occurred less frequently with subsequent Periochip place-ments. Periochip is the only locally applied nonantibiotic antimicrobialapproved by the FDA as an adjunct to SRP procedures for the reduction ofprobing pocket depth or as part of a routine periodontal maintenanceprogram. The recommendation for use adjunctive to SRP involves isolationof the periodontal pocket of 5 mm or more, drying the surrounding area,and grasping the Periochip with a forceps and inserting the chip, curvedend first, into the pocket to its maximum depth. The chip can be maneu-vered further into position with a plastic instrument. One site can be treatedper chip.

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Antibiotics

Locally applied antimicrobialsTo have a therapeutic effect on the microflora, antimicrobial agents must

reach adequate concentrations to kill or inhibit the growth of targetorganisms. The drug of choice has to reach the site where the organisms exist,stay there long enough to get the job done, and not cause harm. Mouthrinsesdo not reach the depths of periodontal pockets, whereas irrigation can deliverdrugs to the base of the pocket. Because the gingival crevicular fluid (GCF)in the pocket is replaced about every 90 seconds, the duration of exposureduring subgingival irrigation is short, and topically applied subgingivalagents are rapidly washed out. With regard to the systemic administration ofantibiotics to patients with periodontitis, early research suggested thatdoxycycline administered systemically [35,36] was highly concentrated in theGCF at levels 5 to 10 times greater than found in serum. Furthermore,tetracyclines show substantivity because they bind to the tooth structure andare slowly released as still-active agents. Even this supposed hyperconcen-tration of the drug in the GCF resulted in a level of antibiotic to which manyorganisms were not susceptible. More recent work has challenged earlierfindings of hyperconcentration of tetracyclines in the GCF. In the 2 hoursafter the administration of a single dose of tetracycline (250 mg), minocycline(100 mg), or doxycycline (100 mg), the concentration of these tetracyclineswas found to be highest in the plasma, intermediate in the GCF (doxycyclineachieving the highest levels), and lowest in the saliva [37]. Furtherexperimentation may be required to resolve this issue because there wasa great deal of variability in the average GCF concentrations (0–8 mg/mL) inthis study, and steady-state levels of the drug were never achieved. To addressthe issue of reaching adequate concentrations at the base of the pocketwith adequate duration, controlled local delivery of antimicrobials wasdeveloped (Table 1).

Dental research has provided us with a better understanding of themicrobial etiology and the nature of periodontitis. Periodontitis, initiated bybacteria, frequently appears in localized areas in the patient’s mouth or isconfined to localized areas by treatment. These infected localized areas lendthemselves well to treatment with a controlled local delivery system using anantimicrobial [38]. Antimicrobial agents may be applied directly to thepocket, thereby eliminating many of the adverse side effects associated with

Table 1

Periodontal antimicrobial delivery systems

Objective

Mouthrinse or

toothpaste

Local

irrigation

Systemic

delivery

Controlled

delivery

Reach the pocketO4 mm Poor Good Good Excellent

Adequate concentration Poor Good Fair Excellent

Adequate duration Poor Poor Fair Good

619NONSURGICAL APPROACHES

systemic delivery of antibiotics. Nonresorbable and resorbable intrapocketdelivery systems have been used. There is evidence that local delivery ofsustained-release antimicrobials may lead to improvements in periodontalhealth, although a few side effects such as transient discomfort, erythema,recession, transient resistance, and allergy have been reported. Oral can-didiasis has been reported in a small number of cases with local tetracyclinedelivery.

Systems have been developed for the release of all three commerciallyavailable tetracyclines at high doses and at a regular rate over a 10- to 14-dayperiod. The first such FDA-approved system, Actisite, was developed by Dr.Max Goodson in 1983 [39]. Actisite consisted of a nonresorbable polymerfiber of ethyl vinyl acetate, 25% saturated with tetracycline hydrochloride.Use of this product resulted in substantially higher doses of tetracycline in thepocket (1590 mg/mL in the GCF and 43 mg/mL in the tissue) than could beachieved by systemic dosing (2–8 mg/mL). A local concentration of 30 mg/mLeliminates most pathogenic bacteria associated with periodontal diseases.When using locally applied antimicrobials, the area being treated is saturatedwith doses of the therapeutic agent that can be sustained for prolongedperiods. Despite the high doses of drug that are achieved locally, serum levelsof the drug do not exceed 0.1 mg/mL. The use of a singly applied tetracyclinefiber as an adjunct to SRP proved to be more effective than scaling alone atreducing bleeding on probing, pocket depth, and achieving attachment gainas early as 60 days after placement, with additional improvements at 6months. At 6 months after a single application of Actisite, the respectiveaverage results for SRP plus tetracycline fiber therapy versus SRP only were1.81 mm versus 1.08 mm for pocket depth, 1.56 mm versus 1.08 mm forattachment gain, and 63% versus 50% for bleeding on probing reductions[40]. Subsequent studies concluded that SRP combined with full-mouthActisite therapy versus SRP alone resulted in increased bone density (þ2.43computer-assisted densitometric image analysis [CADIA] versus �2.13CADIA) and increased alveolar bone height (þ0.24 mm versus �0.29 mm)at 6 months after therapy [41]. Despite its demonstrated efficacy, this productis no longer marketed to the dental community. Actisite was difficult to use,requiring considerable operator skill, and because it was not resorbed,a second visit had to be scheduled to remove it. In attempts to improve on easeof placement of local antimicrobials into the pocket and to obviate the needfor a second visit to remove the product, bioabsorbable delivery systems weredeveloped.

Atridox. The second FDA-approved locally delivered tetracycline to bedeveloped was Atridox (Atrix Laboratories, Inc., Fort Collins, Colorado),a 10% formulation of doxycycline in a bioabsorbable, ‘‘flowable’’ poly-DL-lactide and N-methyl-2-pyrrolidone mixture delivery system that allows forcontrolled release over 7 days. This system is supplied in two prefilledsyringes to be mixed at chairside and applied subgingivally to the base of the

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pocket through a cannula. The flowable polymer gel of Atridox fills andconforms to pocket morphology, then solidifies to a waxlike substance aftercontact with GCF. Significant reductions (60%) in anaerobic pathogens aresustained for up to 6 months after placement of Atridox [42]. In subjectswith chronic adult periodontitis, the application of this doxycycline gel atbaseline and 4 months later resulted in reductions in probing depths (1.3mm) and gains in clinical attachment (0.8 mm) equivalent to SRP alone at 9months after baseline [43]. An important finding of these studies was thatfor the Atridox treatment group, smoking status did not seem to affect theoutcome of clinical parameters such as probing depth reductions and clinicalattachment level gains, whereas smokers and even former smokers did notrespond as well to mechanical therapy alone [44]. A recent study supportsthese findings, indicating that locally applied Atridox improves the healingfollowing nonsurgical therapy in smokers [45]. The side effect profile wasequivalent to placebo. Despite the results of the initial phase III studies, it islikely that this agent will be used not as a monotherapy for the managementof periodontal disease but as an adjunct to mechanical therapy.

Removal of the offending plaque and calculus deposits by SRP hasproved to be effective. Disruption of the biofilm improves on the efficacy ofantimicrobial agents. Phase IV studies conducted to support improvedoutcomes by using Atridox as an adjunct to scaling have demonstratedincremental benefits of use [46]. One arm of a 6-month study involvedinitiating therapy with ultrasonic scaling combined with Atridox, followedat 3 months by SRP alone in those sites with pocket depths that remainedO5 mm. Results showed that this approach was at least as effective inimproving probing depths and clinical attachment levels as the second armof the study that involved SRP alone followed at 3 months by ultrasonicscaling and Atridox in those sites with pocket depths that remained O5 mm.The main difference between the two arms of this study was that theresponse was far more dramatic at 3 months for the combination therapythan the SRP alone, but the addition of either therapy at the 3-monthinterval allowed for equivalence to be achieved by 6 months.

Atridox is the only resorbable site-specific locally applied antibioticproven to promote clinical attachment gains and reduce pocket depths,bleeding on probing, and levels of pathogenic bacteria. Clinical use of theproduct involves twisting and locking together two syringesdone witha purple stripe containing Atrigel and the second containing 50 mg ofdoxycycline hyclatedand pushing the contents of one into the other, backand forth, mixing for about 90 seconds (or about 100 times). Aftercompletion of mixing, all contents are placed into the syringe with thepurple stripe and a blunt metal or plastic cannula is screwed on to the endand bent to resemble a periodontal probe. The cannula tip is placed into thebase of the pocket and the Atridox is expressed, withdrawing the syringe asthe pocket begins to fill. When the pocket is filled, the product is separatedfrom the cannula by pressing the tip up against the tooth. A wet plastic

621NONSURGICAL APPROACHES

instrument may be used to tap the product lightly into the pocket if it isdesirable to place additional Atridox into the site. A single syringe ofAtridox can be used to treat multiple sites (approximately 8–12), the numberof sites depending on the severity of the disease.

Arestin. With regard to minocycline, there is a non–FDA-cleared ointmentproduct of 2% (wt/wt) minocycline hydrochloride known as Dentamycine(Wyeth, United Kingdom) or PerioCline (Sunstar, Japan) and marketed ina number of countries. In a four-center double-blinded randomized trialconducted in Belgium, the minocycline ointment was applied once every 2weeks for four applications due to insufficient sustained-release properties.Probing depth reductions were significantly greater in the SRP plusminocycline group versus SRP alone, whereas there was only a trendtoward improvement in clinical attachment levels and bleeding indices in theSRP plus minocycline treatment group [47]. In a long-term 15-month study,after placement of the gel subgingivally at baseline, at 2 weeks, and at 1, 3, 6,9, and 12 months, results showed a statistically significant improvement forall clinical and microbiologic parameters for adjunctive minocyclineointment [48].

A minocycline microsphere system (Arestin; Johnson and Johnson, NewBrunswick, New Jersey) has been approved by the FDA. The Arestinmicrospheres are bioadhesive, bioresorbable, allow for sustained release, andare administered as a powder with a proven safety record. Arestin is indicatedas an adjunct to SRP procedures for reduction of pocket depth in patientswith adult periodontitis. Arestin may be used as part of a periodontalmaintenance program, which includes good oral hygiene and SRP. Insubjects with chronic adult periodontitis, the application of minocyclinemicrospheres three times over the course of 9 months (at baseline and at 3 and6 months) resulted in an average of 0.25 mm improvement above averageprobing depth reductions seen with SRP alone at month 9 [49].When the dataare stratified in accordance with severity of baseline probing depths, there are20% improvements in mild sites, 40% inmoderately diseased sites, and 100%in severely diseased sites compared with SRP alone. SRP plus Arestin resultedin a greater percentage of pockets showing a change of pocket depthR2 mmandR3 mm compared with SRP alone at 9 months. The data also show thatfor pockets of 5 to 7 mm at baseline, greater reductions in pocket depthsoccurred in pockets that were deeper at baseline. In smokers, the meanreduction in pocket depths at 9 months was less in all treatment groups thanin nonsmokers; however, SRP plus Arestin produced significantly greaterpocket depth reductions than SRP alone at 6 and 9 months [49].

Arestin is delivered to sites of 5 mm or greater through a cartridge(containing 1 mg of minocycline hydrochloride) attached to a handle. Thetip is removed from the cartridge and placed subgingivally, and the handle isdepressed to express the Arestin from the cartridge. A single site can betreated with a single cartridge.

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Periochip. For information on Periochip, see the section ‘‘Locally appliedantiseptic.’’

Systemic antimicrobialsFor the most part, systemic antimicrobial therapy has been reserved for

advanced cases of periodontitis: (1) for sites that have not responded asexpected to debridement with or without locally applied chemotherapeuticagents and/or host modulatory agents, and (2) for patients diagnosed withaggressive forms of periodontitis that demonstrate progressive periodontaldestruction. Systemic antibiotics may be recommended as adjuncts toconventional mechanical therapy, but strong evidence for their use as amonotherapy has not been developed. There appears to be a consensus thatsystemic antimicrobial therapy should be reserved for situations that cannotbe managed with mechanical therapy alone (with or without locally appliedantimicrobials or antiseptics), such as severe or acute infections, early-onsetperiodontal diseases, aggressive types of periodontitis, and recurrent orrefractory cases [50]. For these special situations, randomized double-blindedclinical trials and longitudinal assessments of patients indicate that systemicantimicrobials may be useful in slowing disease progression [51]. Acutenecrotizing ulcerative gingivitis can be cured with metronidazole [52], andaggressive adolescent periodontitis associated with Actinobacillus actino-mycetemcomitans can be controlled or eradicated with metronidazole-amoxicillin combination therapy [53].

Systemic antibiotic therapy has the advantage of simple, easy adminis-tration of a drug or combination of drugs to multiple periodontal sites andextradental oral sites that may harbor periodontal pathogens. Thedisadvantages include uncertain patient compliance, the inability of thedrugs to achieve adequate concentration at the site of infection, increased riskof adverse drug reactions, the potential for the selection of multipleantibiotic-resistant organisms, and the overgrowth of opportunistic patho-gens [50]. Microbial analysis can be used to determine the specificantimicrobial susceptibility pattern of the suspected pathogens, can help tochoose the appropriate antibiotics, and may be followed-up with additionaltesting to verify the elimination or suppression of the putative pathogens. Forsome clinicians, microbial analysis may be reserved for cases that arerefractory to an initial course of antimicrobial therapy. Common antibiotictherapies for the treatment of periodontitis include metronidazole, 500 mg,three times a day for 8 days; clindamycin, 300 mg, three times a day for8 days; doxycycline or minocycline, 100 to 200 mg, every day for 21 days;ciprofloxacin, 500 mg, twice a day for 8 days; azithromycin, 500 mg, everyday for 4 to 7 days; metronidazole and amoxicillin, 250 mg of each drug, threetimes a day for 8 days; and metronidazole and ciprofloxacin, 500 mg of eachdrug, twice a day for 8 days [54]. For adult patients with acute periodontalabscesses, an antibiotic regimen as an adjunct to incision and drainage isamoxicillin (1 g loading dose followed by 500 mg, three times a day for

623NONSURGICAL APPROACHES

3 days), with patient follow-up re-evaluation. For patients with allergies tob-lactam drugs, antibiotic regimens include azithromycin (1 g loading dosefollowed by 500 mg, every day for 2 days) or clindamycin (600 mg loadingdose followed by 300 mg, four times a day for 3 days).

The host modulatory approach

Host modulation is a new term that has been incorporated into dentaljargon and has not been well defined. The definition of host from a medicaldictionary reads ‘‘the organism from which a parasite obtains itsnourishment or in the transplantation of tissue, the individual who receivesthe graft’’ [55]. The definition for the term modulation is ‘‘the alteration offunction or status of something in response to a stimulus or an alteredchemical or physical environment’’ [55]. In diseases of the periodontium thatare initiated by bacteria, it is clear that the host is the individual whoharbors these pathogens; however, it was not clear for many years that itwas possible to modulate the host response to these pathogens. Hostmodulation with chemotherapeutics or drugs is an exciting new adjunctivetherapeutic option for the management of periodontal diseases. The conceptof host modulation is fairly new to the field of dentistry but is universallyunderstood by most physicians who routinely apply the principals of hostmodulation to the management of a number of chronic progressivedisorders including arthritis and osteoporosis.

A number of host modulatory agents have been investigated in clinicaltrials for their potential use as adjuncts to mechanical nonsurgicalperiodontal therapy. These agents have included the systemic (flurbiprofen)and topical (ketoprofen) use of nonsteroidal anti-inflammatory drugs, thesystemic use of subantimicrobial-dose doxycycline (SDD; Periostat [Colla-Genex Pharmaceuticals, Newtown, Pennsylvania]), and the systemic use ofbisphosphonates (Fosamax). The only systemic host modulatory agentapproved by the FDA for adjunctive use in conjunction with nonsurgicalperiodontal procedures is Periostat. The points of intervention of theseagents in the host response can be seen in Fig. 2. In addition, a number oflocal host modulatory agents have been investigated in clinical trials fortheir potential use as adjuncts to surgical procedures not only to improve onwound healing but also to stimulate regeneration of lost bone, periodontalligament, and cementum, restoring the complete periodontal attachmentapparatus. These agents have included enamel matrix proteins (Emdogain),bone morphogenetic proteins 2 and 7, growth factors (platelet-derivedgrowth factor and insulin-like growth factor), and tetracyclines. The initiallocal host modulatory agent approved by the FDA for adjunctive use duringsurgery was Emdogain; platelet-derived growth factor combined witha resorbable synthetic bone matrix (GEM 21S) was approved recently bythe FDA. Emdogain has also been studied as an adjunct to nonsurgicaltherapy. The results of a 3-month double-blinded, split-mouth, controlled

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and randomized study do not support the use of Emdogain during routinenonsurgical debridement of periodontal pockets as measured 3 months postSRP [56]. Histologic evaluation of human intrabony defects followingnonsurgical periodontal therapy with and without application of Emdogainfailed to show periodontal regeneration with subgingival application ofEmdogain [57]. The clinical utility of host modulation for nonsurgicalprocedures in clinical practice is limited in the remainder of this article to theuse of SDD (Periostat).

SDD is a 20-mg dose of doxycycline (Periostat) that is FDA approvedand ADA accepted. It is indicated as an adjunct to SRP in the treatment ofchronic periodontitis. It has been evaluated as taken twice daily for up to9 months of continuous dosing in clinical trials. The duration of use mayvary from patient to patient. A risk factor assessment in addition to clinicalevaluation of patients can help guide the practitioner with regard to lengthof use and need for repeat use. A minimum of 3 months of host modulatorytherapy is suggested for reasons described later. Current clinical studies insusceptible patient populations such as osteopenic women are investigatingextended continuous use of up to 2 years. The 20-mg twice per day doseexerts its therapeutic effect by enzyme, cytokine, and osteoclast inhibition,rather than by any antibiotic effect. Research studies have found noevidence of any detectable antimicrobial effect on the oral flora or thebacterial flora in other regions of the body and have identified clinicalbenefit when SDD is used as an adjunct to SRP. At the present time, SDD isthe only FDA-approved, ADA-accepted host modulatory therapy specif-ically indicated for the treatment of chronic periodontitis.

SDD works so well as a host modulatory agent because of its pleiotropiceffects on multiple components of the host response (see Fig. 2). The only

Bacterial

Products

Host

Cells

Prostaglandins

Cytokines(IL-1,IL-6, TNF)

MMPs

Bone

Resorption

Connective

Tissue

Breakdown

Bacterial

ComponentHost Response Component

Clinical

Sequelae+ =

Pockets

and

CAL

Tooth

Mobility

and

Loss

Mechanical TherapyAntimicrobialsAntiseptics Osteoclasts

NSAIDS

Periostat

BisphosphonatesPeriostat

Periostat

Fig. 2. Points of intervention for nonsurgical therapy. CAL, clinical attachment loss; IL,

interleukin; NSAIDS, nonsteroidal anti-inflammatory drugs; TNF, tumor necrosis factor.

625NONSURGICAL APPROACHES

enzyme (MMP) inhibitors that have been tested for the treatment ofperiodontitis are members of the tetracycline family of compounds. In anearly study using these different tetracyclines, Golub et al [58] reported thatthe semisynthetic compounds (ie, doxycycline) were more effective thantetracycline in reducing excessive collagenase activity in the GCF of adultperiodontitis patients. Recent clinical trials have focused on doxycyclinebecause it was found to be a more effective inhibitor of collagenase thanminocycline or tetracycline [59,60] and because of its safety profile,pharmacokinetic properties, and systemic absorption. In an effort toeliminate the side effects of long-term tetracycline therapy (especially theemergence of tetracycline-resistant organisms), SDD capsules were preparedand tested [61]. Each capsule contained 20 mg of doxycycline compared withthe commercially available 50- and 100-mg antimicrobially effective capsules.In multiple clinical studies conducted using SDD, there has not been adifference in the composition or resistance level of the oral flora [62,63], andrecent studies demonstrate no appreciable differences in fecal or vaginalmicroflora samples [63]. In addition, these studies have demonstrated noovergrowth of opportunistic pathogens such as Candida in the oral cavity,gastrointestinal, or genitourinary systems.

With regard to MMP inhibition, Golub et al [64] reported that a 2-weekregimen of SDD reduced collagenase in GCF and in the adjacent gingivaltissues surgically excised for therapeutic purposes. Subsequent studies usingSDD therapy adjunctive to routine scaling and prophylaxis indicated thatafter 1 month of treatment, there were continued reductions in the excessivelevels of collagenase in the GCF but after cessation of SDD administration,there was a rapid rebound of collagenase activity to placebo levels,suggesting that a 1-month treatment regimen with this host modulatoryagent was insufficient to produce a long-term benefit [65]. In contrast,during the same study, a 3-month regimen produced a prolonged drugeffect without a rebound in collagenase levels to baseline during the no-treatment phase of the study. The mean levels of GCF collagenase weresignificantly reduced (47.3% from baseline levels) in the SDD-treatedgroup versus the placebo group, which received scaling and prophylaxisalone (29.1% from baseline levels). Accompanying these reductions incollagenase levels were gains in the relative attachment levels in the SDD-treated group [65,66]. Continuous drug therapy over a period of severalmonths appears to be necessary for maintaining near normal collagenaselevels over prolonged periods. It is reasonable to speculate, however, thatthese MMPs will eventually reappear in susceptible patients, and thoseindividuals having the most risk factors and the greatest microbialchallenge will require more frequent host modulatory therapy than otherpatients.

A series of double-blinded placebo-controlled studies of 3, 6, and 9months’ duration showed clinical efficacy based on the reduction of pocketdepth, gains in clinical attachment levels, biochemical efficacy based on the

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inhibition of collagenase activity, and protection of serum alpha1-antitrypsin (a naturally occurring protective mediator) from collagenaseattack in the periodontal pocket [59,67,68]. Golub et al [69] showed that a2-month regimen of SDD significantly decreased the level of bone-typecollagen breakdown products (pyridinoline cross-linked carboxyterminaltelopeptide of type I collagen) and MMP-8 and MMP-13 enzyme levels(neutrophil and bone-type collagenase) in adult periodontitis subjects,providing biochemical evidence of reduction of bone resorption to supportcomputer-assisted subtraction radiography data [70,71], the latter providingevidence of a reduction in the loss of alveolar bone height after 12 months oftherapy with SDD.

A 9-month randomized, double-blinded placebo-controlled trial con-ducted at five dental centers demonstrated clinical efficacy and safety of SDDversus placebo as an adjunct to SRP, the ‘‘gold standard’’ of periodontaltherapy. Again, the benefits of host modulatory therapy in addition tomechanical therapy were seen, with statistically significant reductions inprobing depths, bleeding on probing, gains in clinical attachment levels, andthe prevention of disease progression [72,73]. In a discontinuation study inwhich SDD administration was discontinued after 9 months of continuoustherapy, the incremental improvements demonstrated in the SDD group weremaintained for at least 3 months post treatment. There was no rebound effectin pocket depth reductions or clinical attachment level gains; in fact, thereappeared to be slight continued improvements in both of these clinicalparameters [72,73], presumably due to the enhanced clinical status of thepatients who benefited from adjunctive Periostat and the known persistenceof doxycycline in the bone and soft tissue of the periodontium. The clinicalrelevance of such findings confirms the utility of an MMP inhibitor in themanagement of adult periodontitis.

Recent phase IV clinical studies have been performed that have revealedclinical and biochemical success using SDD in different populations ofsusceptible individuals, including subjects who are genetically susceptible[74]; subjects who have severe generalized periodontitis [75], diabetes [76,77],or osteoporosis [78]; subjects who are institutionalized geriatric patients [79];and smokers [80]. The use of SDD in these at-risk patient populationssignificantly improved clinical response to SRP, and in the case of smokers,the subjects who were treated with SRP plus SDD experienced probing depthreductions and clinical attachment level gains equivalent to, and in somestudies superior to, the response seen in nonsmokers who were treated withSRP alone [80]. In addition, it becomes apparent that the use of systemic hostmodulatory therapy by the dentist may not only improve the patient’speriodontal condition but also provide systemic benefits for other in-flammatory disorders with related tissue destruction, such as arthritis,cardiovascular disease, dermatologic conditions, diabetes, osteoporosis, andso forth. Dental studies have reported dramatic reductions in hemoglobinA1c levels (a long-term marker of glycemic control) in addition to

627NONSURGICAL APPROACHES

improvements in clinical parameters in diabetic subjects treated with SDDplus SRP compared with SRP alone [76,77]. Dental studies in osteoporoticwomen have reported reductions in the loss of alveolar bone height and bonedensity (as measured by computer-assisted densitometric image analyses) inaddition to clinical attachment level gains and no attachment loss in subjectstreated with SDD plus SRP compared with subjects treated with SRP alonewho experienced no attachment level gains and loss of attachment ina number of sites over the 12 months of the study [78]. Another assumptionthat can be made is that patients who are currently being prescribed hostmodulatory agents by their physicians, such as nonsteroidal anti-inflamma-tory drugs, bisphosphonates, or tetracyclines, and newer agents targetingspecific cytokines for the management of medical conditions may beexperiencing periodontal benefits from these systemically administeredmedications.

In the clinical trials of SDD (20-mg dose), the drug was well tolerated, andthe profile of unwanted effects was virtually identical in the SDD and placebogroups [73,75,81,82]. SDD is indicated in the management of chronicperiodontitis [68,73,83,84]. SDD should not be used in conditions such asgingivitis or periodontal abscess, or whenever an antibiotic is indicated. SDDcan be used in aggressive periodontitis cases that are being treatednonsurgically [75]. Furthermore, emerging studies have supported the efficacyof SDD as an adjunct to periodontal surgery [85]. SDDmay also be of benefitin cases that are refractory to treatment or in patients with risk factors such assmoking or diabetes in whom the treatment response might be somewhatlimited. SDD is contraindicated in anyone with a history of allergy orhypersensitivity to tetracyclines. It should not be given to pregnant orlactating females or children less than 12 years old (because of the potentialfor discoloration of the developing dentition). Doxycycline may reduce theefficacy of oral contraceptives, so advice should be given to use alternativeforms of birth control, if necessary. There is a risk of increased sensitivity tosunlight (manifested by an exaggerated sunburn) seen with higher doses ofdoxycycline, but this has not been reported in any of the clinical trials at thesubantimicrobial dose. A typical prescription for Periostat (20-mg doxycy-cline tablets) is for at least 3 months (180 tablets, 1 tablet twice a day untilcomplete), and refills may be provided for longer courses of therapy.

SDD treatment can also be combined with the local delivery ofantibiotics to the periodontal pocket by way of sustained delivery systems.The two treatments target different aspects of the pathogenic process: localdelivery systems deliver antimicrobial concentrations of an antibacterialagent directly to the site of the pocket, whereas SDD is a systemic hostresponse modulator. Thus, combining these two complementary treatmentstrategies is another example of how antibacterial therapy (ie, SRP pluslocally applied antibiotics) can be combined with host modulatory therapy(SDD) to maximize the clinical benefit for patients. Preliminary results froma 6-month 180-patient clinical trial designed to evaluate the safety and

628 RYAN

efficacy of SDD combined with a locally applied antimicrobial (Atridox)plus SRP versus SRP alone demonstrated that patients receiving thecombination of treatment experienced more than a 2-mm improvement inmean attachment level gain and pocket depth reduction, which was highlystatistically significant (P!0.0001) compared with SRP alone.

Clinical application

The author has implemented a three-pronged approach to periodontaltherapy in her clinical practice (Fig. 3). The initial visit by a patient includesa medical and dental history, a risk assessment profile, periodontal charting,and radiographic analysis. The patient must be made aware of the fact thatperiodontal disease is not curable but that it can be treated and wellcontrolled with constant monitoring by the dentist/hygienist and goodpatient compliance. The patient must also be informed of the need forperiodontal therapy, which should not be considered optional or elective butnecessary to promote not only good oral health but also good generalhealth, as recent studies have suggested.

Initial therapy consists of risk reduction strategies (see Box 2). Modifica-tion of any risk factors such as smoking, nutrition, stress, contributing

Diagnosis of Periodontitis, Risk Factor Assessment

Initial Therapy

Antimicrobial ApproachOHI, Antiseptics, SRP

Host Modulatory ApproachHMT

Re-Evaluation

UnstableProbing Depths ≥ 5 mm

BOP

StableProbing Depths < 5 mm

Minimal BOPMaintenance

Therapy (3 month Recall)

Unstable Stable SPTActive Therapy

Localized Sites Generalized Sites

SRP, Local Anti-MicrobialTherapy, HMT Surgery, SRP, HMTSPT SPT

Re-Evaluate

Unstable Stable

Maintenance TherapySPT

AdditionalTherapy

Repeat, SurgeryRe-Evaluate

Unstable Stable

SPTAdditionalTherapy

Systemic Antibiotics

RiskReduction

Fig. 3. Periodontal therapy treatment algorithm. BOP, bleeding on probing; HMT, host

modulatory therapy; OHI, oral hygiene instruction; SPT, supportive periodontal therapy

(reinforce OHI, scaling, antiseptics).

629NONSURGICAL APPROACHES

medications, faulty restorations, poor oral hygiene, and poor diabetic controlshould be addressed at this time. Oral hygiene instructions are extremelyimportant andmust be reinforced continuously over the course of therapy; theuse of adjunctive antiseptic agents is often employed. SRP is the core ofnonsurgical therapy, with anesthesia administered as needed. At-home oralhygiene and in-office SRP approaches are designed to reduce the bacterialload. In addition, an initial course of hostmodulatory therapy (Periostat)maybe prescribed to reduce excessive levels of enzymes, cytokines, andprostanoids, especially in susceptible patients as identified by risk assessment.A patient’s refusal or inability to modify contributing risk factors is animportant consideration for treatment planning and evaluation of therapeuticresponses. In the case of adjunctive chemotherapies, the more risk factors andthe poorer the hygiene, the greater the need for antiseptics, antibiotics, andhost modulation of longer duration or repeat therapy in the future.

After completion of initial therapy, re-evaluation is the next step (seeFig. 3). At this point, the decision is made to continue with active(additional) therapy or to place the patient in the maintenance phase oftherapy. If all probing depths are !5 mm and there is minimal bleeding onprobing and gingival inflammation, then the decision is made to place thepatient in the maintenance phase of therapy. The patient is typicallymaintained on the host modulatory agent through the first maintenancevisit. If the treated sites remain stable for this 3-month period, then thepatient is removed from the host modulatory agent and placed in the typicalmaintenance program (3- to 4-month visits) until the need for additionalactive therapy is required. If there are probing depths R5 mm at re-evaluation, then the therapeutic approach may differ depending on thenumber of sites per quadrant and radiographic assessment of the sites.

Typically for isolated sites with probing depths R5 mm at re-evaluation,a nonsurgical approach may include rescaling the sites and placement ofa locally applied antimicrobial agent (ie, Atridox, Arestin, or Peiochip), withthe continued adjunctive use of the host modulatory agent. Sites treatedwith locally applied antimicrobials should be re-evaluated at 3 months anda decision can be made by the clinician as to whether an additionalapplication of the same locally applied antimicrobial may be used oranother locally applied antimicrobial may be administered, and so forth.Clinicians must use their clinical judgment. If this treatment is insufficient toachieve adequate pocket depth reduction or if there are multiple sites ina quadrant with probing depths R5 mm, then a surgical approach may beindicated to reduce the probing depths through resective or regenerativetechniques. After all probing depths are !5 mm, the patient is placed in themaintenance phase of therapy as described earlier.

In certain patients with aggressive periodontitis or in those trulyrefractory to the therapy described previously, the use of systemicantimicrobials or additional host modulatory agents in a polypharmacologicapproach can be considered. Microbial and antibiotic susceptibility testing

630 RYAN

may be helpful in these situations. Examples of additional host modulatoryapproaches have included low doses of nonsteroidal anti-inflammatorydrugs (flurbiprofen), which demonstrated incremental benefits in a smallclinical study [86] or low doses of bisphosphonates, which have not yet beeninvestigated in combination in human clinical studies but have shownincremental benefits in animal studies of osteoporosis. Patients who aredifficult to manage, who are most susceptible with multiple risk factors, orwho present with moderate to severe disease requiring comprehensiveperiodontal treatment planning should be referred to the periodontalspecialist for care and close monitoring.

To improve our ability to make appropriate treatment decisions forpatients undergoing periodontal therapy, it would be extremely useful tohave access to the types of diagnostic tests that are available to our medicalcolleagues. Therapeutic technologies have surpassed our ability toadequately diagnose active versus inactive lesions, identify subtle changesin the tissues and, thereby, prevent additional loss of attachment and bone.Studies have shown that SRP alone, although effective at improving clinicalparameters such as probing depths that are routinely used to assess theoutcome of periodontal procedures, may not be sufficient to reduce excessivelevels of many of the underlying destructive mediators, particularly insusceptible patients. In the future, dental diagnostics currently beingdeveloped to aid in clinical assessment of patients may be performed ina centralized diagnostic laboratory facility rather than at chairside. Oralsamples and perhaps even blood samples collected from patients and sent toa centralized diagnostic laboratory will include plaque samples for microbialassessments, buccal cheek swabs for genetic testing, and GCF (single ormultiple sites or full-mouth rinse collections) and saliva for analysis of hostresponse mediators such as enzymes, cytokines, and prostanoids. Theinformation gained from improved quantitative diagnostics will be used tocreate a profile of the patient’s riskdnot only for oral disease but alsopotentially for systemic disordersdto determine the patient’s level ofperiodontal disease activity, aid in treatment planning decisions, and bettermonitor the patient’s response to therapy. Until such diagnostic techniquesare made available, clinicians have no choice but to rely on clinical judgmentto determine the most appropriate course of therapy.

Summary

Periodontal pathogens and destructive host responses are involved in theinitiation and progression of periodontitis in the individual at risk fordisease. Therefore, the successful long-term management of this disease mayrequire a treatment strategy that integrates therapies that address all of thesecomponents. There is now overwhelming evidence for the role of bacterialpathogens and host-derived MMPs, cytokines, and other mediators in thedestructive processes of periodontal disease, distinguishing them as viable

631NONSURGICAL APPROACHES

targets for chemotherapeutic adjunctive approaches. The introduction ofnovel adjunctive therapies to enhance the efficacy of existing mechanicalprocedures has contributed favorably to an integrated approach for thelong-term clinical management of periodontitis.

Finally, as the era of periodontal medicine evolves, the additional benefitsof adjunctive local and systemic antimicrobials and systemic host modulatoryapproaches need to be considered. In particular, host modulators used tomanage periodontal disease by inhibiting mediators of host tissue destructionsuch as MMPs, cytokines, and prostanoids may have additional beneficialeffects on systemic diseases such as cardiovascular disease, diabetes, andosteoporosis. The surgeon general’s report [87] recognizes ‘‘the mouth as amirror of health or disease, as a sentinel or early warning system, as anaccessible model for the study of other tissues and organs, and as a potentialsource of pathology affecting other systems and organs.’’ The findingsdiscussed in this article with regard to the use of therapeutics to better managechronic periodontal disease may have applications to other associatedsystemic diseases such as diabetes, cardiovascular disease, stroke, respiratorydisease, and adverse pregnancy outcomes. The proper management ofperiodontitis may prove to have an impact on general health, makinga significant contribution to human welfare.

Acknowledgments

The author would like to acknowledge Laura Bertolotti for her assistancein the organization of this manuscript.

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and periodontal disease. A review. J Clin Periodontol 2003;30(9):761–72.

[85] ChoiDH,Moon IS, Choi BK, et al. Effects of sub-antimicrobial dose doxycycline therapy on

crevicular fluid MMP-8, and gingival tissue MMP-9, TIMP-1 and IL-6 levels in chronic

periodontitis. J Periodontal Res 2004;39(1):20–6.

[86] Lee HM, Ciancio SG, Tuter G, et al. Subantimicrobial dose doxycycline efficacy as a matrix

metalloproteinase inhibitor in chronic periodontitis patients is enhanced when combined

with a non-steroidal anti-inflammatory drug. J Periodontol 2004;75(3):453–63.

[87] US Department of Health and Human Services. Oral health in America: a report of the

surgeon generaldexecutive summary. Rockville (MD): US Department of Health and

Human Services, NIDCR, NIH; 2000. p. 1–13.

636 RYAN

Diagnostic and TherapeuticStrategies for the Management of the Diabetic PatientMaria Emanuel Ryan, DDS, PhD

1

The bridge between oral and systemichealth has been reinforced during

the past decade by multiple publicationsdescribing this important connection inboth dental and medical journals. Theoral focus of these publications hasbeen on periodontal diseases, which arethe most common dental conditions. Itis known that a number of systemic dis-eases, including diabetes, can increasean individual’s risk for developingperiodontitis, which is a chronic andprogressive disease with no known cure.

However, periodontal disease is certain-ly treatable and may even be preventedby appropriate risk assessment and riskreduction strategies. Conversely, untreat-ed periodontal disease has been linkedto an increased risk for developing certainsystemic conditions as well as difficultiesin managing certain systemic conditions.The medical management of diabetes isaffected by the presence of chronicinfections, such as those seen in patientswith periodontitis. These links betweenoral and systemic health have led to the

ABSTRACT

The bridge between oral and systemic health exists and becomes more concrete as data con-tinue to emerge in support of this relationship. The medical management of diabetes is affected by the presence ofchronic infections, such as periodontitis. This article reviews the pathogenesis of periodontal disease as it relates todiabetes. The author discusses patient susceptibility in terms of risk and recommends risk assessment to determineoptimal treatment strategies. Patients with poorly controlled diabetes are at greater risk for developing periodontitis.The opportunity for systemic exposure to periodontal pathogens and pro-inflammatory mediators associated withperiodontitis is discussed relative to their specific effects on patients with diabetes. The importance of good metabol-ic control in terms of risk for developing long-term complications of diabetes is presented and the impact of perio-dontitis on achieving adequate metabolic control is described. Special considerations for the management of patientswith diabetes in the dental office are reviewed, including the signs and symptoms of diabetes, risk assessment fordiabetes, and the challenges of “tight control” with insulin and oral agents with regards to hypoglycemia. It is recom-mended by the author that a thorough medical history of the patient be obtained, that the patient’s medicationsare known, that the dentist consults with the patient’s physician to assess the patient’s glycemic control, and thatthe patient’s blood glucose levels and dietary intake be monitored before treatment. Finally, the author reviews thelong-term complications of diabetes, particularly the oral complications that can affect overall health. The authorconcludes with the belief that the treatment of periodontal diseases should not be considered optional or elective but,instead, should be a necessary and integral part of a patient’s overall health care program.

Maria Emanuel Ryan, DDS, PhDProfessor and Director of Clinical Research • School of Dental Medicine • State University of New York at Stony Brook • Stony Brook, New York

INSIDE DENTISTRY VOL. 2 (SPECIAL ISSUE 1)

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2 INSIDE DENTISTRY VOL. 2 (SPECIAL ISSUE 1)— INTERNATIONAL CONSENSUS STATEMENT—MARIA EMANUEL RYAN

belief that the treatment of periodontaldiseases should not be considered option-al or elective but, instead, should be anecessary and integral part of a patient’soverall health care program.

THE PATHWAY TOPERIODONTAL DISEASEUnderstanding the pathway to periodon-titis is essential because it enables clini-cians, researchers, and patients to considerthe possible mechanisms by which oral–systemic connections occur (Figure 1).1

It is a microbial challenge to the host orperson with poor oral hygiene that initi-ates the cascade of events that can resultin periodontal breakdown. The pres-ence of bacterial endotoxins, antigens,and other virulence factors stimulate thehost immuno-inflammatory response.Neutrophils are recruited to the site ofthe infection to address the pathogenicmicrobes, which then invoke an antibodyresponse. In more resistant individuals,

these events lead to the development oflocalized reversible inflammation, knownas gingivitis. In more susceptible individ-uals, very high levels of pro-inflammatorymediators—known as cytokines, prosta-noids, and matrix metalloproteinases—will be produced by the host, leading toconnective tissue breakdown and bonemetabolism changes associated with thebone loss that is pathognomonic toperiodontitis. In the clinical setting, thiscascade of events presents as the signs ofdisease: increases in probing depth, lossof clinical attachment, and radiographicevidence of bone loss. So the questionbecomes, “Who are these susceptibleindividuals?”

Genetics plays a significant role inwho may be susceptible. Studies haveshown that at least 50% of all cases ofperiodontal disease have some geneticcomponent.2 In addition, there are anumber of environmental and acquiredrisk factors that put patients at greaterrisk (Table 1). Risk assessment is impor-

tant because it has been recognized thatthe more risk factors a patient has, themore likely he or she is to develop thedisease. There is often more than anadditive effect, there is a synergisticeffect between these risk factors.

Identification and consideration ofthese risk factors is critical to successfulperiodontal treatment because they canaffect the onset, the rate of progression,and the severity of periodontal disease.In addition, these risk factors may deter-mine treatment strategies and explainvariability in the therapeutic responsesof patients. Risk factor assessments canalter the way patients are viewed by thepractitioner, leading to a decision processbased on risk. The primary goal of thepractitioner would be risk reduction. Asimple example of this would be improve-ments in oral hygiene since it has longbeen known that poor oral hygieneincreases the risk of disease. A clinicianmay proceed with caution if a patientpresents with multiple risk factors. In

Figure 1 The pathway to periodontal disease through which clinicians consider how oral–systemic connections occur.PMN = polymorphonuclear leukocytes. LPS = lipopolysacharides. MMPs = matrix metalloproteinases.

INSIDE DENTISTRY VOL. 2 (SPECIAL ISSUE 1)— INTERNATIONAL CONSENSUS STATEMENT—MARIA EMANUEL RYAN 3

addition, patients begin to be viewed interms of risk when considering howtreatment should proceed. Dependingon the type of risk (eg, the presence of asystemic condition such as diabetes),the clinician will interact more with ourmedical colleagues in an attempt toreduce the risk.

Ultimately, as part of a risk assessment,risk reduction for periodontal diseaseneeds to be considered. Risk reductionstrategies are listed in Table 2. Obviously,the more risk factors a patient has, themore frequent his or her dental visitsshould be, including more intensiveperiodontal therapy and follow-up main-tenance. Certain risk factors can be modi-fied while others cannot (eg, heredity).Once this is determined, the appropri-ate therapeutic regimens can be utilized,including the use of adjunctive medica-tions that may be administered to thepatients that have been referred to as“perioceutics” in the past.3 Locallyapplied or systemically delivered anti-microbials may be one choice; hostmodulatory agents are another, which maybe ideal for patients who cannot reducetheir risk (such as patients who have agenetic predisposition). For smokers,smoking cessation is the obvious firststep, but what if the patient will not stopsmoking? Cutting back on tobacco usemay help, but other strategies wouldneed to be considered in those patientswho cannot or will not stop smoking.In diabetic patients, the patient’s physi-cian should be consulted to help thepatient achieve better metabolic controlof his or her diabetes to facilitate anoptimal response to periodontal thera-py. Patients who are unable to controltheir diabetes will be much more diffi-cult for the oral health care provider tomanage and may require the use ofadjuncts to traditional mechanical ther-apy, such as antimicrobials and hostmodulatory therapy as part of theirtreatment regimen.

ORAL–SYSTEMIC EXPOSUREThe presence of periodontitis can pres-ent a significant challenge to the entirebody. The surface area of the pocketepithelium is estimated to be the equiv-alent to the surface area of the palm of

one or even two hands, depending onthe severity of the periodontal disease. Ifa patient had an equivalent challengeanywhere else on the body, it certainlywould be of concern. The problem isthat many people do not have any signsor symptoms of periodontal disease,

resulting in an often silent disease. Inaddition, the presence of deep inflamedpockets is not directly visible to thosewho have periodontal disease; therefore,they do not recognize the challenge thatexists in the oral cavity. It is importantfor dental practitioners to express this

TABLE 1:

Risk Factors forPeriodontal Disease

Heredity

Family historyPST-test

Smoking

Frequency (current, past)

Diabetes

Duration, control

Stress

Reported by patient

Medications

Calcium channel blockersDilantinCyclosporinKnown to cause dry mouth

Nutrition

Poor oral hygiene

Plaque and calculus

Faulty dentistry

OverhangsSubgingival margins

Hormonal variations

PregnancyIncreased estradiol and

progesteroneMenopause

Decreased estrogenOsteoporosis

Immunocompromise

Human immunodeficiency virusNeutropenia

Connective tissue diseases

Previous history of periodontitis

TABLE 2:

Risk Management forPeriodontal Disease

Heredity

Perioceutics

Smoking

CessationPerioceutics

Diabetes

Improved controlWork with medical doctorPerioceutics

Stress

ManagementPerioceutics

Medications

Change in medicationsWork with medical doctorPerioceutics

Nutrition

Supplements

Poor oral hygiene

Improved oral hygienePerioceutics

Faulty dentistry

Corrective dentistry

Hormonal variations

Consult with medical doctorPerioceutics

Immunocompromise

Consult with medical doctorPerioceutics

Connective tissue diseases

Consult with medical doctorPerioceutics

4 INSIDE DENTISTRY VOL. 2 (SPECIAL ISSUE 1)— INTERNATIONAL CONSENSUS STATEMENT—MARIA EMANUEL RYAN

not only to their patients but also tophysicians because many physicians areoften unaware of the significant chal-lenge that oral infection and inflamma-tion can present to the entire body. Ifthe periodontitis is not treated, thesebacteria will eventually enter into thebloodstream, attracting platelets andputting patients at greater risk for anumber of systemic diseases, includingcardiovascular disease, which is the num-ber one cause of mortality among peo-ple with diabetes.

The systemic exposure to periodon-tal pathogens is a result of the loss of theepithelial integrity within the periodon-tal pockets in people with periodontaldisease, allowing for bacterial penetrationinto the tissues and eventually the blood-stream, resulting in a bacteremia. If perio-dontal disease is left untreated, everytime the patient eats, he or she will havea recurrent transient bacteremia. Oralpathogens have been found throughoutthe body, in fetal cord blood, and inatheromatous plaques.4 Endotoxins can

also penetrate into these tissues result-ing in endotoxemia. Many of the pro-inflammatory mediators present inpatients with periodontitis can be foundnot only within the gingival crevicularfluid flowing out of their pockets butalso within the gingival tissues and alveo-lar bone and eventually in the blood-stream, resulting in elevated levels ofInterleukin-1 and 6, tumor necrosisfactor, and prostanoids. Figures 2A and2B demonstrate the differences in thevascularity of healthy versus inflamedgingival tissue.5 When there is inflam-mation, there is much more vascularity,a greater chance for bacteremias andendotoxemias to occur, and morechances for the inflammatory mediatorsto enter into the system. Once in thesystem, all of these factors can have aprofound effect on the patient, particu-larly the diabetic patient, leading toinsulin resistance and resulting in diffi-culties in achieving metabolic control ofthe diabetes.

DIABETESThe link between periodontal and sys-temic health is a two-way street, particu-larly when it comes to periodontitis anddiabetes mellitus. There are a number ofsystemic diseases and conditions thatcan increase a patient’s susceptibility toperiodontitis, and top on the list is dia-betes mellitus. Conversely, periodontalinfections can have an impact on sys-temic health, and diabetes tops the listonce again in that if you have untreatedperiodontitis, it can impede the meta-bolic control of diabetes.

In 1995, there were approximately110 million people with diabetes world-wide. However, if the numbers are pro-jected to the year 2025, it is estimatedthat the number of people in the worldwith diabetes will approximate 300 mil-lion, which is considered a global epi-demic (Figure 3).6 In the United Statesin 1995, there were approximately 12million people with diabetes, and it isestimated that in 2025 the numbers willreach more than 20 million (Figure 4).6

In China, the estimated rise is muchmore rapid, going from the same 12 mil-lion in 1995 to nearly 40 million peoplewith diabetes by the year 2025. In Europe,

A. B.

Figures 2A and 2B The differences in the vascularity of (A) healthy gingival tissue versus (B)inflamed gingival tissue.

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INSIDE DENTISTRY VOL. 2 (SPECIAL ISSUE 1)— INTERNATIONAL CONSENSUS STATEMENT—MARIA EMANUEL RYAN 5

the numbers of people with diabetes fallsomewhere between those reported inthe United States and China. The greatestnumbers of people with diabetes in theworld is expected in India, where by theyear 2025 it is estimated that more than55 million people will have diabetes. Itis believed that the greatest growth ofpatients will be in Asia where it is pre-dicted by the year 2010, more than 60%of all patients suffering from diabeteswill live.

Why is there such a rise? The reasonsinclude increasing longevity, change indemographics, and genetic predisposi-tions. Rising urbanization and changes inlifestyle play a role as well as an increasedprevalence of obesity. In the United States,obesity is known to play a role, wheremore than 60% of the adult populationis considered to be either overweight orobese. There are approximately 18 mil-lion people with diabetes currently inthe United States, with 798,000 new casesdiagnosed yearly.7 In addition, 90% to95% of all cases in the United States aretype 2. This presents a substantial healthcare problem in light of the long-termcomplications of the disease. Diabetes isthe leading cause of blindness in adults.End-stage renal disease, cardiovascularcomplications, and nontraumatic ampu-tations are additional complications, andthe health care costs are immense: $98.2billion annually.8

The Diabetes Control and Compli-cations Trial (DCCT) found that improvedcontrol of blood glucose reduces therisk of a number of long-term compli-cations, particularly retinopathy, nephro-pathy, and neuropathy (Figure 5).9 Datafor reductions in cardiovascular diseaseare emerging as well.10 According to theDCCT trial, the risk of sustained retino-pathy progression (gauged by glycosy-lated hemoglobin [HbA1c]) in years offollow-up is in those patients with high-er HbA1c levels (Figure 6).11 As a resultof these findings, the major objective ofphysicians is reducing and maintaininglow levels of HbA1c, which is a long-term marker of control (unlike bloodglucose which fluctuates daily as weeat). HbA1c levels of 4% to 6% are nor-mal, <7% is considered good diabetescontrol, 7% to 8% is moderate control,and with >8% action is suggested to

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Figure 4 The projected number of diabetics to the year 2025 worldwide. The greatest number ofdiabetic people in the world will be in India.

Figure 5 Results from the Diabetes Control and Complication Trial found the improved control ofblood glucose reduces the risk of some long-term complications.9,10 (Figure 2006 © ThomsonProfessional Postgraduate Services®. All rights reserved.)

6 INSIDE DENTISTRY VOL. 2 (SPECIAL ISSUE 1)— INTERNATIONAL CONSENSUS STATEMENT—MARIA EMANUEL RYAN

improve control. Currently, blood levelsof glucose and HbA1c can be deter-mined chairside. Glycated serum pro-tein levels are an emerging intermediatemarker of control, but HbA1c levels aremost commonly used today to determinelong-term control in the diabetic patient.It is the primary objective of most physi-cians to keep these levels low to preventlong-term complications.

DENTISTS AND DIABETESHow does this relate to the practicingdentist? Every dentist will encounterpatients with diabetes. In the UnitedStates, where 6% to 7% of the popula-tion is diabetic, a dental practice of 2500patients will most likely have 150 to 175diabetic patients, and 50% of thosepatients may not even be aware theyhave the disease. It may be the dentistwho picks up certain signs of diabetesand refers the patient to the physician.Dentists and physicians need to worktogether to better manage their patientswith diabetes. In developing relation-ships with the physicians, the dentistmay find that through referrals theirpractice will grow and they may be treat-ing many more patients with diabetes.

Signs and Symptoms/Risk AssessmentIt is important for dentists to recognizethe classic signs and symptoms of dia-betes, which should be taught as an

integral part of the dental educationprocess. Once diagnosed, it is equallyimportant for the dentist to know howthe diabetic patient should be appropri-ately managed in the dental office.Classic signs and symptoms include poly-dipsia, polyuria, nocturia, polyphagia,unexplained weight loss, general fatigue,and increases in infections (Table 3).Other symptoms are leg cramps, numb-ness in the extremities, impotence, andblurred vision. In a risk assessment fordiabetes, age is a factor with mostdiabetics >45 years of age (becausemost patients are type 2). However, thenumber of overweight adolescents withtype 2 diabetes is growing rapidly,which is associated with the risk factorof obesity. There is a very strong geneticpredisposition that occurs with type 2diabetes; therefore, a family history ofthe patient is important. Other indica-tors include racial descent, gestationaldiabetes or a history of delivering a baby>9 pounds, a history of impaired glu-cose tolerance and impaired fasting glu-cose, hypertension, and dyslipidemia.Gestational diabetes is a concernbecause many of the women who devel-op gestational diabetes will eventuallydevelop type 2 diabetes. Of patientswho have gestational diabetes, 30% to50% will develop type 2 diabetes within10 years. Once it is determined that apatient may be diabetic, he or sheshould be referred to the physician, andlaboratory diagnostic criteria (Table 4)

will be conducted in the physician’soffice for a definitive diagnosis.

In an undiagnosed patient, particu-larly a type 1 diabetic, a life-threateningincident, such as ketoacidosis, can occur,which may be precipitated by systemicinfection or stress. Therefore, dentistsalso need to know the signs and symp-toms of ketoacidosis: nausea, vomiting,abdominal pain, dehydration, changes

TABLE 3:

Classic Signs and Symptoms of Diabetes Mellitus

• Polydipsia, polyuria, nocturia, polyphagia

• Unexplained weight loss

• General fatigue

• Increased infections

• Leg cramps

• Numbness in the extremities

• Impotence

• Blurred vision

TABLE 5:

Precipitants, Signs,and Symptoms of Hypoglycemia

Precipitants

• Missed meals and snacks• Excessive insulin dose• Intensive treatment regimens or “tight control”• Inattention to warning symptoms• Recent exercise• Alcohol and drugs

Signs and Symptoms

• Confusion• Shakiness, tremors• Agitation• Anxiety• Sweating• Dizziness• Tachycardia• Feeling of “impending doom”• Seizures• Loss of consciousness

TABLE 4:

Laboratory Diagnostic Criteria for Diabetes Mellitus

Laboratory Methods (to be confirmed on subsequent day)

Classic symptoms and casual (nonfasting) plasma glucose ≥200 mg/dLFasting plasma glucose ≥126 mg/dLTwo-hour postprandial glucose ≥200 mg/dL during an oral glucose tolerance testTest performed with 75 g of anhydrous glucose dissolved in water

Categories of fasting plasma glucose (FPG)

FPG <110 mg/dL = normal fasting glucoseFPG ≥110 mg/dL and <126 mg/dL = impaired fasting glucoseFPG ≥126 mg/dL = provisional diagnosis of diabetes (confirmed on next day)

Categories of two-hour postprandial glucose (2hPG)

2hPG <140 mg/dL = normal glucose tolerance2hPG ≥140 mg/dL and <200 mg/dL = impaired glucose tolerance2hPG ≥200 mg/dL = provisional diagnosis of diabetes (confirmed on next day)

INSIDE DENTISTRY VOL. 2 (SPECIAL ISSUE 1)— INTERNATIONAL CONSENSUS STATEMENT—MARIA EMANUEL RYAN 7

in respiration, altered mental status, andpossible coma. These patients requireimmediate medical attention and addi-tional laboratory findings to confirmketoacidosis.

Insulin and HypoglycemiaThe only hormone that lowers blood glu-cose is insulin. As previously mentioned,physicians work diligently to reducehyperglycemia to prevent the long-termcomplications of diabetes. An unfortu-nate event associated with intensive med-ical treatment regimens or “tight control”is low blood glucose or hypoglycemia.There are a number of hormones thatcan raise blood glucose, including:glucagon, catecholamines (epinephrine),glucocorticoids (cortisol), and growthand thyroid hormones. Many emergencykits in the dental office contain glucagonfor the management of extreme cases ofhypoglycemia. The important thingfor the dentist to know about the differ-ent types of insulin is the time of peakactivity after administration, because thisis when patients are more prone to devel-op hypoglycemic episodes. Patients oninsulin are susceptible to hypoglycemia asare patients on certain oral agents, espe-cially the second generation sulfony-lureas, which produce a relatively highincidence of hypoglycemia.

Some of the precipitants of hypo-glycemia include missed meals andsnacks (it is important to ask patients ifthey have eaten), intensive treatmentregimens, an excessive insulin dose,inattention to warning symptoms, recentexercise, alcohol use, and drug use(Table 5). If the signs and symptoms ofhypoglycemia (Table 5) are known tothe dentist, he or she can detect it earlyand treat it very rapidly.

What preventative measures can betaken to help avoid this? A thoroughmedical history, consideration of thepatient’s medications, the avoidance ofvisits at the peak activity periods ofinsulin and oral medications, consulta-tion with the physician to assess thepatient’s gylcemic control, and of moni-toring the dietary intake and blood glu-cose levels with a glucometer beforetreatment. In addition, it is important torecognize the signs and symptoms of lowblood glucose and to administer a carbo-

hydrate source in a timely manner. Onemajor problem experienced with diabet-ic patients is that the greater the numberof hypoglycemic events, the more likely itis that the patient will develop a condi-tion known as hypoglycemia unaware-ness. Basically, this means that thepatient will not experience the early signsand symptoms of hypoglycemia and mayexperience seizures and loss of con-sciousness fairly rapidly. Table 6 lists thesteps for emergency treatment of thepatient with hypoglycemia. Because adentist may treat many people with dia-betes, he or she should be prepared tomanage the hypoglycemic patient.

Complications Compound ComplicationsThe classic complications of diabetes(angiopathy, nephropathy, retinopathy,neuropathy, and wound healing prob-lems) are of major concern to physiciansand they should be to dentists as well. Inthe assessment of the diabetic patient,the dentist needs to know of any long-term complications of the disease becausethe more complications a diabetic patienthas, the more likely the patient is todevelop additional complications. Oncethe patient’s complications are deter-mined, his or her medical and dentaltreatment can center on preventing thedevelopment of additional complications.

Periodontitis—The SixthLong-Term Complicationof DiabetesThere exists a two-way street betweendiabetes and periodontal disease in thatdiabetics are at a greater risk for develop-ing infections and these infections canimpair a diabetic’s metabolic control.12

There are a number of periodontally rel-evant host-response abnormalities thatoccur in diabetic patients, which increas-es their risk for developing periodontitissuch as vascular abnormalities, imbal-ances in lipid and collagen metabolism,and neutrophil dysfunction. In particu-lar, the presence of glycated proteins suchas advanced glycation end products(AGEs) can put a patient at higher riskfor developing periodontitis as well asother long-term complications of dia-betes. These altered proteins developthrough a nonenzymatic process; asproteins bathe in blood with very highglucose levels they actually become glycat-ed. These AGEs then interact with recep-tors on a number of different cells knownas receptors for AGEs, or RAGEs, whichresults in an increase in pro-inflammatorymediators that can lead to the connectivetissue breakdown seen in periodontitis.In addition, a number of growth factorsare produced, which can result in theproliferation of cells and matrix knownto play a role in retinopathy.

TABLE 6:

Emergency Treatment of Hypoglycemia

Establish blood glucose level with glucometer (if possible)

In awake patient, give 15 g of carbohydrate orally as either:

120–180 mL (4–6 oz) fruit juice or sugared soda3–4 teaspoons of table sugarhard candycake frosting in a tube

In patient unable to use oral route with IV in place either:

25–30 mL of 50% dextrose (D50)1 mg glucagon

In patient unable to use oral route without IV in place:

1 mg glucagon subcutaneously or intramuscularly

Monitor patient for 1 hour after recovery

Seek emergency medical assistance if patient does not respond

8 INSIDE DENTISTRY VOL. 2 (SPECIAL ISSUE 1)— INTERNATIONAL CONSENSUS STATEMENT—MARIA EMANUEL RYAN

Salvi and colleagues analyzed thegingival crevicular fluid of diabeticpatients and found a fourfold increase ofpro-inflammatory mediators comparedwith nondiabetic control subjects.13

This was believed to be a result of thehypersecretion of these factors bymonocytes in the diabetic subjects. Thesubjects in this study were determinedto be at risk for periodontitis becauseof excessive inflammation with anequivalent bacterial burden. Because ofthe major role these mediators play inthe progression of their periodontaldisease, future dental diagnostics mayinclude measuring the levels of the pro-inflammatory mediators, which couldparticularly benefit diabetic patients.This test may take the form of paperstrips placed into the periodontal pockets(Figure 7) from which the levels of cyto-kines, prostanoids, and enzymes in thegingival crevicular fluid can be measured;or the collective levels from all of the sitespresent in a patient may be measuredusing a mouth rinse technique.

In the future, dentists will most likelydevelop a closer relationship with physi-cians to monitor patients for changes inoral health. Figures 8 through 10 showexamples of diabetic patients in whomperiodontal disease is present. For thetype 1 adolescent diabetic patient inFigure 8, the physician could most likelyview the gingival inflammation during acursory oral examination and refer thepatient to the dentist for therapy. InFigure 9, the 55-year-old man with type2 diabetes has obvious recession andloss of attachment. However, the patientin Figure 10 exemplifies a type 2 diabet-ic patient who has significant perio-dontitis, which may never be picked upby a cursory oral examination. In thiscase, probing depths and radiographswould be necessary for the detection ofperiodontitis. However, improvementsin biochemical diagnostics for perio-dontitis might allow physicians, nurses,and even patients to send samples to acentralized laboratory for evaluationand preliminary detection of perio-

dontal inflammation and breakdownwith subsequent referral to the oralhealth care provider for a complete oralevaluation and treatment.

Diabetic patients can also develop oralconditions other than periodontitis,including candidiasis and caries. It is oftenfound that the level of disease does notcorrelate with the levels of bacteria orplaque (Figure 11). There can be very sig-nificant inflammation leading to abscessformation in patients with diabetes. Also,the enlargement of the parotid glands canlead to xerostomia or dry mouth, whichcontributes to the development of can-didiasis and burning mouth and tongueas well as caries (Figure 12). The adminis-tration of antifungal agents may be neces-sary for the management of candidiasis.The management of oral burning symp-toms can include the maintenance ofadequate oral hydration and restrictionson the intake of caffeine and alcohol. Inaddition, preventive measures for infec-tion and delayed wound healing need tobe taught at all levels, because diabetics

Figure 8 Dentition of an adolescent girl withtype 1 diabetes, poor metabolic control, andsevere periodontitis.

Figure 7 Paper strips may be used to measurethe levels of the pro-inflammatory mediators.

Figure 9 This 55-year-old man with type 2diabetes has obvious recession and loss ofattachment.

Figure 10 A type-2 diabetic patient who hassignificant periodontitis, which may never bepicked up by a cursory oral examination.

Figure 11 There can be very significantinflammation leading to abscess formation inpatients with diabetes.

Figure 12 The enlargement of the parotidglands can lead to xerostomia, which con-tributes to the development of candidiasis,burning mouth and tongue, and caries.

INSIDE DENTISTRY VOL. 2 (SPECIAL ISSUE 1)— INTERNATIONAL CONSENSUS STATEMENT—MARIA EMANUEL RYAN 9

are at greater risk for infection anddelayed wound healing. The preventivemeasures involve frequent dental visitsto assess plaque control, risk assessmentprofiles to identify risk, preoperative andpostoperative antibiotic therapy if nec-essary, and the avoidance of compound-ing risk factors such as smoking.

MANAGING PERIODONTALDISEASE IN THE DIABETIC Periodontal health is particularly impor-tant in people with diabetes because it isknown that bacterial infections decreaseinsulin-mediated glucose uptake by theskeletal muscle leading to whole-bodyinsulin resistance. The presence ofbacterial endotoxins and host-derivedcytokines induce insulin resistance anddecrease insulin action. Untreated perio-dontal disease results in chronic inflam-mation that leads to increased insulinresistance, reduced glucose tolerance,and an increased risk of diabetic compli-cations. Two studies have demonstratedthat diabetic subjects with severe perio-dontitis are at greater risk for developingnephropathy and cardiovascular disease,which can both affect mortality in thispatient population.14,15 In an 11-yearfollow-up of subjects, Thorstensson andcolleagues demonstrated that diabeticswith severe periodontitis had a greaterprevalence of proteinuria indicative ofnephropathy and a greater number ofcardiovascular complications.14 Theseoral–systemic connections in diabeticshave been confirmed most recently bySaremi and colleagues,15 who reportedthat periodontal disease is strongly pre-dictive of mortality from ischemic heartdisease and diabetic nephropathy in apopulation of Pima Indians with type 2diabetes. In an 11-year follow-up, theage- and sex-adjusted death rates of thetype 2 diabetics increased with the sever-ity of their periodontitis. There is nodoubt that optimal oral health is essen-tial to the medical management of thediabetic patient.

CONCLUSIONImportant factors to consider in assess-ing the periodontal status of patientswith diabetes are the patient’s degree of

metabolic control, the duration of thedisease, the presence of other long-termcomplications, and concurrent risk fac-tors. Patients with more than one riskfactor have an even greater risk fordeveloping periodontitis. Nonmicrobialrisk factors amplify the host response,which is most evident in individualswith diabetes and can be compoundedby concurrent risk factors such assmoking and genetics. Therapeuticstrategies should include reduction ofbacterial infection, modulation of thehost response, and risk reduction tohelp improve therapeutic outcomesin the susceptible diabetic patient.Improving diagnostics is important forearly detection and intervention. Inaddition, for improved patient care,treatment plans should be individual-ized, patient education and motivationare paramount, and routine mainte-nance is necessary.

In conclusion, diabetes mellitus has asignificant impact on the tissues through-out the body, including the oral cavity.Poorly controlled diabetes increases therisk for periodontitis. Periodontal infec-tion and the treatment of periodontal dis-ease can alter glycemic control. Earlyintervention and treatment of perio-dontitis may help to prevent the develop-ment of long-term complications ofdiabetes, such as nephropathy and cardio-vascular disease thereby having an impacton mortality. The future will include agreater need for dental and medical prac-titioners to communicate and partner.The group practice of the future will mostlikely be the dentist and the physicianworking very closely together. Periodontaltreatment may eventually be covered bymedical insurance, which would includeconsultations, diagnostics, and thera-peutics. The data emerging from studiesof diabetic patients are important forestablishing the absolute necessity forperiodontal health. The treatment ofperiodontal disease should not be con-sidered an option or elective and thedemand for preventive care will increase.There is an urgent need for knowledgetransfer, which will be facilitated by theintegration of the emerging data andconcepts into both dental and medicalschool curriculum at all levels.

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