Periodontal Disease and Overall Health: A Clinician's Guide

Periodontal Diseaseand Overall Health:A Clinician’s GuideEditorsRobert J. GencoRay C. WilliamsSupported through an educational grant from

Periodontal Diseaseand Overall Health:A Clinician’s GuideRobert J. Genco, DDS, PhDDistinguished Professor of Oral Biology and MicrobiologySchools of Dental Medicine and Medicine and Biomedical SciencesVice Provost, Office of Science,Technology Transfer and Economic OutreachDirector, Clinical Research Center of the Buffalo Clinical andTranslational Research CenterState University of New York at BuffaloBuffalo, NY, USARay C. Williams, DMDProfessor and Dean, School of Dental MedicineStony Brook UniversityStony Brook, NY, USAPROFESSIONAL AUDIENCE COMMUNICATIONS, INC.Yardley, Pennsylvania, USA

iiPeriodontal Disease and Overall Health: A Clinician’s GuideCopyright © 2010 by the Colgate-Palmolive Company. All rights reserved.No part of this publication may be used or reproduced in any form or by any means, orstored in a database or retrieval system, without prior written permission of the Colgate-Palmolive Company. Making copies of any part of this book for any purpose other thanyour own personal use is a violation of United States copyright laws.ISBN-13: 978-0-6152-8508-5ISBN-10: 0-6152-8508-2Published by …Professional Audience Communications, Inc.PO Box 243Yardley, Pennsylvania 19067 USAEditorial Quality Control: Teri S. SiegelCopyediting/Proofreading: Michelle RizzoLayout and Design: E. Allen DownsCover Design: Horizons Graphic DesignIndexing: Allegheny Writing & Publishing Services, LLCPublisher: Stephen M. SiegelPrinted in the United States of AmericaLast digit is the print number: 9 8 7 6 5 4

iiiCONTRIBUTORSSilvana P. Barros, DDS, MS, PhDResearchAssociateProfessorCenterforOralandSystemicDiseasesUniversityofNorthCarolinaSchoolofDentistryDepartmentofPeriodontologyChapelHill,NC,USAPeter Mark Bartold, BDS, DDSc, PhD, FRACDS (Perio)Director,ColgateAustralianClinicalDentalResearchCentreProfessorofPeriodonticsUniversityofAdelaideDepartmentofDentistryAdelaide,AustraliaYiorgos A. Bobetsis, DDS, PhDLecturer,DepartmentofPeriodontologyUniversityofAthensSchoolofDentistryAthens,GreeceWenche Sylling Borgnakke, DDS, MPH, PhDAssistantResearchScientistDepartmentofCariology,RestorativeSciencesandEndodonticsUniversityofMichiganSchoolofDentistryAnnArbor,MI,USADawn J. Caster, MDNephrologyFellowDivisionofNephrologyDepartmentofInternalMedicineUniversityofLouisvilleSchoolofMedicineLouisville,KY,USANoel M. Claffey BDS, MDent Sc, FDS, FFD, FTCDProfessorofPeriodontologyDentalSchoolandHospitalTrinityCollegeDublinDublin,IrelandRobert J. Genco, DDS, PhDDistinguishedProfessorofOralBiologyandMicrobiologySchoolsofDentalMedicineandMedicineandBiomedicalSciencesViceProvost,OfficeofScience,TechnologyTransferandEconomicOutreachDirector,ClinicalResearchCenteroftheBuffaloClinicalandTranslationalResearchCenterStateUniversityofNewYorkatBuffaloBuffalo,NY,USAWilliam V. Giannobile, DDS, DMedScNajjarProfessorofDentistryMichiganCenterforOralHealthResearchDepartmentofPeriodonticsandOralMedicineUniversityofMichiganSchoolofDentistryAnnArbor,MI,USARicardo A. Gómez, MDAssociateProfessorDepartmentofObstetricsandGynecologyP.UniversidadCatólicadeChileHospitalSóterodelRíoClínicaSantaMaríaSantiago,ChileDana T. Graves, DDS, DMScProfessorandChairDepartmentofPeriodonticsNewJerseyDentalSchool(UMDNJ)Newark,NJ,USAYing Gu, DDS, PhDAssistantProfessorDepartmentofGeneralDentistryStonyBrookUniversitySchoolofDentalMedicineStonyBrook,NY,USACasey Hein, BSDH, MBAAssistantProfessor;DivisionofPeriodonticsDirectorofEducation,InternationalCentreonOral-SystemicHealthFacultyofDentistryUniversityofManitobaWinnipeg,Manitoba,CanadaWilliam C. Hsu, MDSeniorPhysicianMedicalDirector,AsianClinicJoslinDiabetesCenterAssistantProfessorofMedicineHarvardMedicalSchoolBoston,MA,USAHeather L. Jared, RDH, MS, BSAdjunctAssistantProfessorUniversityofNorthCarolinaSchoolofDentistryDepartmentofDentalEcologyChapelHill,NC,USA

ivCONTRIBUTORSSrividya Kidambi, MDAssistantProfessorofMedicineMedicalCollegeofWisconsinMilwaukee,WI,USADenis F. Kinane, BDS, PhD, FDSRCS, FDSRCPSDean,UniversityofPennsylvaniaSchoolofDentalMedicinePhiladelphia,PA,USAEvanthia Lalla, DDS, MSAssociateProfessorofDentalMedicineColumbiaUniversityCollegeofDentalMedicineNewYork,NY,USAIra B. Lamster, DDS, MMScDeanandProfessorofDentalMedicineColumbiaUniversityCollegeofDentalMedicineNewYork,NY,USANéstor J. López, DDSProfessorofPeriodontologyUniversityofChileSchoolofDentistrySantiago,ChileJohn H. Loughran, MDFellowofCardiovascularDiseaseUniversityofLouisvilleSchoolofMedicineLouisville,KY,USAPhoebus N. Madianos, DDS, PhDProfessorDepartmentofPeriodontologyUniversityofAthensSchoolofDentistryAthens,GreeceAngelo J. Mariotti, DDS, PhDProfessorandChairDivisionofPeriodontologyTheOhioStateUniversityCollegeofDentistryColumbus,OH,USAJoseph M. Mylotte, MDProfessorofMedicineEmeritusDepartmentofMedicineUniversityatBuffaloSchoolofMedicineandBiomedicalSciencesBuffalo,NY,USATimothy C. Nichols, MDProfessorofMedicine,Pathology,andLaboratoryMedicineDirector,FrancisOwenBloodResearchLaboratoryUniversityofNorthCarolinaatChapelHillChapel,Hill,NC,USASteven Offenbacher, DDS, PhD, MMScOraPharmaDistinguishedProfessorofPeriodontalMedicineDirector,CenterforOralandSystemicDiseasesUniversityofNorthCarolinaSchoolofDentistryChapelHill,NC,USADavid W. Paquette, DMD, MPH, DMScProfessorandAssociateDeanforEducationStonyBrookUniversitySchoolofDentalMedicineStonyBrook,NY,USAShailendra B. Patel, BM, ChB, DPhilProfessorofMedicineDivisionofEndocrinology,MetabolismandClinicalNutritionMedicalCollegeofWisconsinMilwaukee,WI,USAIoannis Polyzois, DMD, MDentCh, MMedSciLecturer,DepartmentofRestorativeDentistryandPeriodontologyDublinDentalSchool&HospitalTrinityCollegeDublinDublin,IrelandHector F. Rios, DDS, PhDAssistantProfessor,DepartmentofPeriodonticsandOralMedicineUniversityofMichiganSchoolofDentistryAnnArbor,MI,USAMaria Emanuel Ryan, DDS, PhDAssociateDeanforStrategicPlanningandExternalAffairsDirectorofClinicalResearchProfessor,DepartmentofOralBiologyandPathologyMedicalStaffUniversityHospitalStonyBrookUniversitySchoolofDentalMedicineStonyBrook,NY,USAFrank A. Scannapieco, DMD, PhDProfessorandChairDepartmentofOralBiologyUniversityatBuffaloSchoolofDentalMedicineBuffalo,NY,USAGeorge W. Taylor, DMD, MPH, DrPHProfessor,DepartmentofCariology,RestorativeSciencesandEndodonticsUniversityofMichiganSchoolofDentistryAnnArbor,MI,USA

CONTRIBUTORSvThomas E. Van Dyke, DDS, PhDProfessor,PeriodontologyandOralBiologyDirector,ClinicalResearchCenterBostonUniversityHenryM.GoldmanSchoolofDentalMedicineBoston,MA,USARay C. Williams, DMDProfessorandDean,SchoolofDentalMedicineStonyBrookUniversityStonyBrook,NY,USAStanley S. Wang, MD, JD, MPHClinicalCardiologistandDirectorofLegislativeAffairs,AustinHeartAdjunctAssistantProfessorofMedicineUniversityofNorthCarolinaChapelHill,NC,USA

CHAPTER 1From the EditorsDear Colleagues:Robert J. Genco, Ray C. WilliamsWe are very pleased to have had the privilege of assembling and editing this textbook,Periodontal Disease and Overall Health: A Clinician’s Guide.The relationship of oral disease to overall disease is certainly not a new concept. For centuries,the role of oral infection and inflammation in contributing to diseases elsewhere in the body hasbeen studied and reported. Going back to ancient times in Greece, we learn that Hippocratestreated two patients suffering from joint pain by removal of teeth. Clearly, this was an earlyexample of oral disease being associated with afflictions elsewhere in the body. Then, movingforward in time from 1912 to around 1950, the era of “focal infection” dominated our thinking.Reports by individuals such as WD Miller, William Hunter, and Frank Billings noted that in theiropinion many of the diseases of humans could be traced to specific foci of infection elsewherein the body, such as the teeth and gums, the tonsils, or the sinuses. While these observationswere not supported by sound scientific evidence, and in fact led to largely incorrect practices,they nonetheless brought attention to the effect of the mouth on the rest of the body.Then in 1989, with a series of intriguing reports from Finland, the current interest in the role oforal health and disease on contributing to general health and systemic conditions was launched.Kimmo Mattila and his coworkers reported that individuals presenting to the emergency roomwith a myocardial infarction were overwhelmingly likely to have periodontal disease. Mightperiodontal disease be a risk factor for cardiovascular disease? Since then, a phenomenal bodyof work has been directed at understanding how periodontal disease might affect distant sitesand organs, and thus have an effect on overall health. Renowned clinicians and scientistsworldwide have studied the relationship of periodontal disease to overall health and disease,and along the way several conferences and workshops have been convened to examine theevidence to date for the relationship between periodontal disease and the risk for systemicconditions. At one of those conferences, in January 2008, we discussed the need for a textbookthat would summarize and put into context the current information on periodontal disease andsystemic disease together for students of dentistry and medicine. Happily for us, Foti Panagakos,Sheila Hopkins, and their team at the Colgate-Palmolive Company agreed to support, throughan educational grant to the publisher, the undertaking of this textbook. We were fortunate tohave assembled a group of respected and scholarly clinicians and scientists who, in eighteenchapters, provide a current and thoughtful perspective on the relationship of periodontal diseaseto systemic conditions.It is a pleasure to present this textbook. We hope you find it useful and that you enjoy it.Sincerely,Robert J. Genco, DDS, PhDRay C. Williams, DMD

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viiiCONTENTSCHAPTER 1Overview 1Robert J. Genco, Ray C. WilliamsCHAPTER 2Overview of Periodontal Disease:Causes, Pathogenesis, and Characteristics 5Ying Gu, Maria E. RyanCHAPTER 3Infection and Inflammation 24Phoebus N. Madianos, Yiorgos A. Bobetsis, Thomas E. Van DykeCHAPTER 4History of the Oral-Systemic Relationship 42Noel M. Claffey, Ioannis N. Polyzois, Ray C. WilliamsCHAPTER 5Diabetes Mellitus: A Medical Overview 55Srividya Kidambi, Shailendra B. PatelCHAPTER 6Association Between Periodontal Diseases and Diabetes Mellitus 83George W. Taylor, Wenche S. Borgnakke, Dana T. GravesCHAPTER 7Atherosclerosis: A Pervasive Disease Affecting Global Populations 105Stanley S. WangCHAPTER 8Association Between Periodontal Disease and Atheromatous Diseases 112David W. Paquette, Robert J. GencoCHAPTER 9Periodontal Disease and Pregnancy Complications 132Silvana P. Barros, Heather L. Jared, Steven OffenbacherCHAPTER 10Oral Health and Diseases of the Respiratory Tract 147Frank A. Scannapieco, Joseph M. Mylotte

ixCONTENTSCHAPTER 11Periodontal Disease and Osteoporosis 162Hector F. Rios, William V. GiannobileCHAPTER 12Association Between Periodontitis and Rheumatoid Arthritis 179P. Mark Bartold, Angelo J. MariottiCHAPTER 13Oral Health, Periodontitis, and Cancer 196P. Mark Bartold, Angelo J. MariottiCHAPTER 14Dental and Medical Comanagement of Patients with Diabetes 216Evanthia Lalla, William C. Hsu, Ira B. LamsterCHAPTER 15Dental and Medical Comanagement of Cardiovascular Disease 237Timothy C. Nichols, David W. PaquetteCHAPTER 16Dental and Medical Comanagement of Pregnancy 250Néstor J. López, Ricardo A. GómezCHAPTER 17Dental and Medical Comanagement of Osteoporosis,Kidney Disease, and Cancer 270Dawn J. Caster, John H. Loughran, Denis F. KinaneCHAPTER 18The Role of the Professional in Educating the PublicAbout the Importance of Oral Health 288Casey HeinINDEX 305

“A person can’t have good general health without good oral health.”—Former US Surgeon General C. Everett Koop

196 Periodontal Disease and Overall Health: A Clinician's GuideCHAPTER 13Oral Health, Periodontitis, and CancerP. Mark Bartold, Angelo J. MariottiINTRODUCTIONPeriodontitis is a chronic immunoinflammatoryreaction to bacteria that residewithin the subgingival plaque biofilm. In additionto pathogenic microorganisms in thebiofilm, genetic and environmental factorscontribute to the pathogenesis of this disease,which results in the destruction of theperiodontal tissues and alveolar bone supportingthe teeth. During these responsesthere is a potential for complications or otherinfluences to impact systemic health via bacteremiaor dissemination of locally producedinflammatory mediators. Bacteremia has thepotential to result in a general systemic inflammatoryresponse. Moreover, locally producedinflammatory mediators disseminatedinto the circulation can result in increasedlevels of inflammatory mediators such astumor necrosis factor alpha (TNF-a), interleukins1 beta and 6 (IL-1 and IL-6), andprostaglandin E 2(PGE 2), as well as acutephaseproteins such as C-reactive protein.This can result in a chronic inflammatoryburden on distant organ systems.Recent studies have demonstrated associationsbetween periodontal disease andseveral systemic diseases, including cardiovasculardisease, diabetes mellitus, adversepregnancy outcomes, respiratory diseases,osteoporosis, and rheumatoid arthritis.With increasing attention being focusedon oral/systemic interactions, studies havesuggested that periodontal disease may be associatedwith increased cancer risk. 1 Interestfor such an association stemmed from earlystudies that investigated the association ofpoor oral health and missing teeth on bothoral cancer and cancer of other systemic organs.While tooth loss may be a poor indicatorof periodontal disease, it has been used as amajor surrogate marker for this disease inolder individuals. 2 Indeed, there are many reasonsfor tooth loss and while it can be a resultof either dental caries or periodontal diseases,age can also be a major contributing factor forthese two conditions. Thus, in early studies,tooth loss in older individuals was assumed tomore likely be a result of periodontal diseasethan caries. In more recent times, such assertionswould almost certainly be challenged.Current understanding would indicate thattooth loss in older individuals may be a resultof perio dontal disease, but this associationmay not always be particularly strong. Thisbeing the case, it is surprising that very fewstudies investigating the role of oral healthand cancer have undertaken specific perio -dontal assessments.The potential interaction between cancerand periodontal disease is important, andmany studies imply that a specific associationbetween periodontitis and cancer (bothoral and general) is feasible. However,larger, more defined studies are needed todetermine whether or not the association canbe confirmed and how this might impact ourunderstanding of the etiology of various cancers,their prevention, and control.In this review, studies included addressedthe association of general oral condition(e.g., oral hygiene, restorations, prostheses,tooth brushing), tooth loss, andperiodontal disease with both oral cancerand cancers of other organs.The educational objectives for thischap ter are:1. Understand the potential associationsbetween oral health, periodontal disease, andvarious cancers.

Chapter 13 Oral Health, Periodontitis, and Cancer 1972. Recognize the limitations of thesestudies with regard to confounding factors inrisk assessment.3. Explore the various hypotheses under -lying the association between oral health,periodontal disease, and cancer.ORAL HeALTH, PeRIODONTITIS,AND ORAL CANCeRSince one of the earliest case-controlreports on oral cancer was published morethan 50 years ago, 3 there have been numerousstudies investigating the role of oralhealth and oral cancer (Table 1). While alcoholand smoking are considered two ofthe most important risk factors for oral cancer,poor oral hygiene and poor dental statushave also been reported to carry a significantrisk for development of oral cancer.Studies of the Relationship BetweenGeneral Oral Health and Oral CancerAn early study to investigate the role ofdentition, diet, tobacco, and alcohol on riskTable 1. Summary of Findings from Studies Published to Date ConcerningTable 1. Relationships Between Oral Conditions and Oral CancerIrregularStudy Tooth Poor Oral Gingival Poor Oral Dental PeriodontalAuthor(s) Design Loss Hygiene Bleeding Condition Check-ups ConditionGraham et al., Case-control Yes Yes — — — —1977 4Zheng et al., Case-control Yes Yes — — — —1990 5Winn et al., Case-control No No No No — —1991 6Marshall et al., Case-control Yes Not — — — —1992 7 SignificantBundgaard et al., Case-control Yes — — — Yes —1995 8Schildt et al., Case-control — — — Yes—for — —1998 9 recurrentinfectionsVelly, 1998 10 Case-control — Yes — Yes—for — —denturerelatedoral soresTalamini et al., Case-control — — Yes Yes — —2000 11Moreno-López, Case control — Yes — — No —2000 12Garrote et al., Case-control Yes — — Yes — —2001 13Campisi and Male Yes Yes — — — —Margiotta, 2001 populationBalaram et al., Case-control Yes — Yes Yes — —2002 14Lissowska et al., Case-control Yes Yes — Yes Yes —2003 15Tezal et al., NHANES — — — — — Yes2005 16Rosenquist et al., Case-control Yes Yes — — — Yes2005 17Tezal et al., Case-control — — — — — Yes2007 18Rezende, 2008 19 Case-control No — — — — Yes

198 Periodontal Disease and Overall Health: A Clinician's Guidefor oral cancer was a case study by Grahamet al. 4 In this study the cases consisted of584 males with cancer of the oral cavityat the Roswell Park Memorial Institute,Buffalo, New York. The controls consistedof 1,222 males with no neoplastic diseasesat the same institute. Interviews werecarried out to obtain information regardingdentition, diet, tobacco, and alcoholconsumption.From this study it was reported that ahigher risk of developing cancer was notedin heavy smokers and heavy drinkers. Poororal hygiene was also associated with increasedrisk for oral cancer. When controlledfor other factors, each of these three factorsdemonstrated a higher risk. When combined,heavy smokers and heavy drinkers with apoor dentition had a risk 7.7 times that ofmen with none of these features.In another case-control study carriedout in Beijing, Zheng et al. 5 investigated thedentition and oral hygiene status for risk oforal cancer. The cases consisted of 404 patientswith histologically confirmed oral cancerand a similar number of control patientswhose hospitalizations were for minor conditions.Subjects were interviewed to obtaininformation regarding alcohol, tobacco use,dentition, and oral hygiene. An oral exam -ination included recording the total numberof teeth, jagged teeth, filled teeth, decayedteeth, and presence of gingivitis or perio -dontal disease. After adjustment for tobaccosmoking, alcohol intake, years of education,gender, and age, males who had lost teethhad an increased risk for oral cancer withan odds ratio (OR) of 2.4 (95% confidenceinterval [CI]:1.3–4.5) if they had replacementteeth, and an OR of 3.7 (CI: 2.2–6.4)if they had no tooth replacement. The datafor females showed an even stronger effectof tooth loss on increased risk for oralcancer, with an OR of 5.6 (CI:12.2–14.5)if they had replacement teeth and an ORof 8.3 (CI:3.5–19.6) if they had no toothreplacement. When oral hygiene was assessed,according to whether the teeth werebrushed or not, men had an adjusted OR of6.9 (CI: 2.5 –19.4) and women an adjustedOR of 2.5 (CI: 0.9–7.5) for increased risk oforal cancer if they did not brush their teeth.The findings were inter preted to indicate thatmissing teeth and poor oral hygiene were riskfactors for oral cancer independent of theknown risks associated with smoking andalcohol consumption.In a study aimed primarily at investigatingthe effect of mouthwash use on oralcancer, Winn et al. 6 studied 1,114 oral cancerpatients from four population-based registriesin the US. Control subjects (n = 1,268) werenoncancerous individuals selected by randomdialing to select individuals of suitableage and gender-matched status. Interviewswere carried out to obtain information regard -ing tobacco use, alcohol use, diet, occupation,and oral health status. The oral health param -eters included the number of teeth, use ofdentures, tooth brushing frequency, andbleeding gingiva. The presence of other oraldiseases as well as the frequency, intensity,duration, and reason for use of mouthwasheswere recorded. A highly significant relationshipbetween mouthwashes of high alcoholcontent and oral cancer was noted for bothmales (OR:1.5; CI:1.1–2.1) and females(OR: 2.0; CI:1.3–3.1). In contrast to mostother studies, this study found no relationshipbetween oral/dental conditions and oralcancer.In another US investigation, Marshall etal. 7 carried out a case-control study in threewestern New York counties to investigatethe contribution of alcohol, dentition, anddiet to oral cancer. The cohort consisted of290 pathologically confirmed cases of oralcancer selected from hospital records, whilematched controls were obtained throughneighborhood matching. Cases and controlswere interviewed to gather information concerningsmoking and tobacco use, alcohol

Chapter 13 Oral Health, Periodontitis, and Cancer 199consumption, dental history (i.e., tooth loss,tooth replacement, oral hygiene, and dentalcheck-up practices), and diet. Compared toindividuals who had not lost any teeth, an increasedrisk for oral cancer was noted forthose individuals who had lost more than 11teeth (OR: 3.9; CI:1.3–11.3). When furtheranalyzed, individuals who smoked cigarettes,drank alcohol, and had lost teeth withouthaving them replaced had an increased riskfor oral cancer (OR:12.8; CI: 4.9–33.8). Theeffect of oral hygiene in this study was determinedto be insignificant.A population-based case-control studyon a Danish population has examined if therisk of oral squamous cell carcinoma couldbe related to occupation, marital status, dentalstatus, and consumption of coffee, tea,alcohol, and tobacco (Bundgaard et al.). 8 Inthis study, the cases consisted of 161 consecutivelyadmitted patients with histologicallyverified intra-oral squamous cell carcinoma.Four-hundred age- and gendermatchedcontrols were selected from theneighborhood. Information was gathered byinterview and no clinical dental examinationwas carried out. After correcting for alcoholand tobacco consumption, dental status wasfound to be a significant factor associatedwith oral squamous cell carcinoma manifestation.Individuals with fewer than five teethhad an OR of 2.4 (CI:1.3–4.1) compared tothose with 15 or more teeth. Furthermore,those individuals who had irregular dentalcheck-ups had an OR of 2.1 (CI:1.3–3.3)compared to those who had regular dentalcheck-ups. While significant, these findingswere determined to be of less importancethan tobacco or alcohol use with regard torisk for oral squamous cell carcinoma.In a case-control study of a Swedishpopulation, Schildt et al. 9 investigated therelationship of oral infections and other dentalfactors for risk of oral cancer. For thisstudy, 410 cases of oral cancer and 410matched controls were sampled. All subjectsreceived a mailed questionnaire concerningdifferent exposure factors of interest for oralcancer including oral infections, dental prostheses,radiographic exposure, restorations,tooth loss, and presence of calculus. Recurrentoral infection was found to be associatedwith increased risk of oral cancer (OR:3.8;CI:2.1–6.9). Other dental factors such asrestorations, dentures, and dental radiographswere of no significance.In a study investigating the relationshipbetween dental factors and risk of upper digestivetract cancer, Velly et al. 10 studied 717patients who had newly diagnosed carcinomasof the tongue, gingiva, floor of mouth,and other parts of the oral cavity from threecenters in Sao Paulo. Controls (noncancerouspatients) were selected from the same institutionsand data were collected from twocontrols matched to each case on the basis ofgender, five-year age group, trimester of hospitaladmission, and study site. Informationcollected by interview included informationon socio-economic variables, health conditions,environmental and occupational exposures,tobacco and alcohol consumption,and diet and oral hygiene. The dental healthinformation was obtained only by interviewand included information concerning brokenteeth, use of dentures and sores causedby dentures, and frequency of tooth brushing.The association between cancer and dentalfactors was assessed using a number ofadjustments for a priori and empirical confounders,including tobacco and alcohol consumption,diet, and socio-economic variables.The risk for all oral cancer in generalwas significantly associated with dentures(OR:0.7; CI:0.52–0.96), history of oral sorescaused by dentures (OR: 0.91; CI: 0.6–1.3), broken teeth (OR:1.42; CI:1.1–1.9) andinfrequent tooth brushing (OR: 2.2; CI:1.6–3.1). Following adjustment of severalconfounders and for all dental factors, onlythe association with tooth brushing frequencywas significant (OR:1.8; CI:1.2–2.8

200 Periodontal Disease and Overall Health: A Clinician's Guideand OR:1.7; CI:1.1–2.8, respectively). Whenassessed on a subsite basis, only less-thandailytooth brushing was a risk for tonguecancer (OR:1.3; CI:0.6–3.0) and other partsof the mouth, including the gingiva (OR:2.4; CI:1.3–4.4). For laryngeal cancer, brokenteeth (OR:1.8; CI:1.3–2.7) and infrequenttooth brushing (OR:1.9; CI:1.2–2.9)were the only significant risk markers. Forpharyngeal cancer, only infrequent toothbrushing (OR:1.5; CI:1.0–2.2) was determinedto be a significant risk factor. The authorsconcluded that poor oral hygiene, dueto infrequent tooth brushing and denturerelatedoral sores, were significant risk factorsfor cancer of the mouth and upper diges -tive tract, and that these associations werenot due to insufficient controlling for confoundingfactors.Talamini et al. 11 carried out a casecontrolstudy on an Italian population investigatingthe effect of oral hygiene and dentitionstatus on oral cancer risk. The cohortconsisted of 132 first-incident cases of oralcancer identified in three northern Italy hospitals.One-hundred and forty-eight hospitalbasedcontrol subjects, who had been admittedfor acute conditions unrelated tosmoking or drinking habits, were also recruitedfor this study. Cases and controlswere interviewed to obtain informationrelating to sociodemographic characteristics,smoking and drinking habits, as well asdental information related to oral hygiene,gingival bleeding, mouthwash usage, wearingof dentures, and dental check-up history.A visual examination determined number ofmissing teeth, presence of calculus, decayedteeth, and mucosal condition. The presenceof gingival bleeding was found to be sig -nificant (OR:3.9; CI:1.2–12.6) when comparedto those whose gingiva did not bleed atall. When the general oral condition wasassessed as being poor on the basis of calculus,decayed teeth, and mucosal irritation,the risk for oral cancer had an OR of 4.5(CI: 1.8–10.9) compared to those who hadgood oral condition. Interestingly, and incontrast to previous studies, the number ofmissing teeth was not found to be a significantfactor.The role of tobacco, alcohol, and oralhygiene in the appearance of oral cancerwas investigated in a case-control study byMoreno-López et al. 12 For this study, thecases consisted of 75 histologically confirmedoral squamous cell carcinomas. Thecontrol group consisted of age- and gendermatchedindividuals in the same healthcarecenter who did not suffer from cancer anddid not have any medical or oral disease ororal manifestation of any systemic disease.An interview was used to obtain informationrelated to demographic variables, tobacco use,alcohol consumption, frequency of dentalcheck-ups, and level of tooth brushing. Nointra-oral examination was carried out.While no statistical significance could befound for dental visits, a significant relation -ship for tooth brushing was found that indicatedthis to be a protective factor (OR: 0.31;CI:0.18–0.56).In a case-control study on a Cuban population,the effect of smoking, alcohol, food,oral hygiene, and sexually transmitted diseaseson risk for oral cancer was evaluated.Garrote et al. 13 compared 200 cases of cancerof the oral cavity and pharynx with 200frequency-matched age and gender controlsfrom the hospital. Interviews were held toobtain information regarding sociodemographiccharacteristics, smoking and alcoholuse, prior occurrence of sexually transmittedinfections, family history of cancer, and dietaryinformation. Indicators of oral hygienewere self-reported via nine specific questions,while the number of missing teeth thathad not been replaced and the general oralcondition with regard to presence of calculus,decayed teeth, and mucosal irritation wereevaluated visually by the interviewing dentist.After allowance for confounding factors

Chapter 13 Oral Health, Periodontitis, and Cancer 201such as education, smoking, and drinkinghabits, individuals with greater than 16 missingteeth had a higher risk of having oralcancer (OR: 2.7: CI:1.2–6.1). In addition,poor general oral condition was more frequentamong cancer cases than controls (OR:2.6: CI:1.2–5.2).In an Indian population derived fromthree regions (Bangalore, Madras, andTrivandrum), Balaram et al. 14 investigatedthe role of smoking, paan chewing, and oralhygiene on risk for oral cancer. In this study,591 incident cases of oral cancer and 582 hos -pital controls that were frequency matchedby age and gender were studied. Informationregarding smoking habits, paan chewing, andoral hygiene habits was obtained by interview.Visual oral inspection allowed assessmentof missing teeth and general oral conditionbased on the presence of calculus, decayedteeth, and mucosal irritation. Regular dentalcheck-ups were found to be protective forwomen but not men (OR: 0.4; CI: 0.19–0.87). Significantly elevated risk for oralcancer for both genders was noted for gingivalbleeding (men = OR:2.8; CI:1.7–4.7and women = OR:3.4; CI:1.8–6.1), havingsix or more missing teeth (men = OR:3.9;CI: 2,5–6.1 and women = OR:7.6; CI: 3.9–14.9), and interviewer-reported poor generaloral condition (men = OR: 4.9; CI:3.1–7.8and women = OR:6.0; CI:3.00–12.00).In a European case-control investigation,Lissowska et al. 15 studied a Polish populationto investigate the effect of smoking,alcohol, diet, dentition, and sexual practiceson risk for oral cancer. The study populationconsisted of 122 patients with histologicallyconfirmed cancer of the oral cavity and pharynx.The controls consisted of 124 age- andgender-matched patients admitted to the hospitalfor non-neoplastic conditions unrelatedto tobacco and alcohol. The subjects wereinterviewed to obtain information regardingdemographics, smoking, alcohol consump tion,family history of cancer, and oral hygiene.After adjusting for smoking and alcohol, andpoor dentition as assessed by number of missingteeth (OR: 9.8; CI:2.3–42.8), the frequencyof dental check-ups (OR:11.9; CI:3.3–42.5) and of tooth brushing (OR: 3.2;CI:1.2–8.5) were found to be the most sig -nificant risk factors for oral cancer. It wascon cluded that poor oral hygiene may bean independent risk factor for oral and oro -pharyngeal cancer.Studies of the Relationship BetweenPeriodontitis and Oral CancerIn the first study in which the perio -dontium was assessed, Tezal et al. 16 used across-sectional analysis of data extractedfrom the Third National Health and NutritionExamination Survey (NHANES III; NationalCenter for Health Statistics 1994). For thisstudy, individuals who were 20 and olderand had at least six natural teeth were included.Subjects requiring antibiotics beforea dental examination were excluded. Perio -dontal measurements included assessmentof clinical attachment loss, while other oralassessments included number of missingteeth, caries, restorations, and the presence ofpartial or full prostheses. Following adjustmentfor age, gender, race, ethnicity, education,tobacco use, alcohol consumption, andoccupational hazard, clinical attachment losswas significantly associated with the presenceof oral tumors (OR: 4.6; CI: 2.3–9.3).Additional analyses considering the interactionsbetween clinical attachment levels(CAL) and smoking indicated that CALwas a significant risk for tumor (OR: 21.76;CI:3.6–131.63) in current smokers, suggestingthat it is a risk modifier. This conceptis strengthened by the observation that CALhad no effect on tumor risk for formersmokers or people who never smoked andhence, is probably not an independent riskfactor.Shortly following the Tezal et al. 16study, Rosenquist et al. 17 published results

202 Periodontal Disease and Overall Health: A Clinician's Guidefrom a study that also used a comprehensiveperiodontal assessment. In this casecontrolstudy of a Swedish population,alcohol consumption, tobacco use, oral hygiene,dental status, and dental radiographicstatus were evaluated for increasing risk fororal cancer. The cases consisted of 132 oraland oropharyngeal cancer patients who wereselected from a population residing in thesouthern healthcare region of Sweden. Ageandgender-matched controls were selectedfrom the same region with no previous cancerdiagnosis (except for skin cancer). Theoral condition was assessed via interviewfor frequency of dental check-ups, visual assessmentof plaque score, modified gingivalbleeding index, number of missing teeth,defective teeth, tooth mobility, furcation involvement,and presence of dentures. A radio -graphic examination of the dentition evaluatedmarginal bone levels, loss of bone alongroot surfaces, angular bony defects, and furcationdefects. A mucosal assessment wasalso provided. In an unadjusted analysis,individuals with average (OR:3.0; CI:1.7–5.1) or poor (OR:10.0; CI:5.1–20.1) oralhygiene, as assessed by plaque scores, weresignificantly at risk for oral cancer. After adjustingfor smoking and alcohol use, individualswith an average plaque score had anOR of 2.0 (CI:1.1–3.6), while a poor plaquescore had an OR of 5.3 (CI:2.5–11.3). Thenumber of missing teeth was also found to bea significant risk factor, with more than 20missing teeth being statistically significant inunadjusted (OR:6.1; CI:2.7–14.0) and adjustedanalyses (OR:3.4; CI:1.4–8.5). Thosewith more than five missing teeth also hadsignificant risk in both unadjusted (OR: 4.8;CI:2.0–11.4) and adjusted (OR:3.1; CI: 1.2–8.2) analyses. Upon radiographic assessment,a high level of marginal bone wasnoted to have an increased risk for oralcancer in unadjusted analyses (OR: 3.00;CI:1.0–8.7); however, this failed to reachsignificance in adjusted analyses. Regulardental check-ups were noted to be associatedwith a decreased risk of oral cancer in adjustedanalyses (OR: 0.4; CI:0.2–0.6).In a subsequent study, Tezal et al. 18 carriedout a case-control study of pre-existingdata for patients seen at the Roswell ParkCancer Center (1999–2005) to assess the roleof periodontitis for risk of tongue cancer.The cases consisted of 54 non-Hispanic Caucasianmales with primary squamous cellcarcinoma of the tongue. Age- and gendermatchednon-Hispanic Caucasian men seenin the same hospital department but notdiagnosed with any cancer or oral dysplasiaserved as the controls (n = 54). The perio -dontal assessment consisted of evaluation ofalveolar bone loss from panoramic radio -graphs. Other dental information includingcaries, restorations, and endodontic treatmentwas determined from the radiographs.Analyses following adjustments for the con -founders of age, smoking habit, and numberof missing teeth indicated that for everymillimeter of alveolar bone loss, there was a5.2-fold increase in the risk of tongue cancer(OR:5.2; CI:2.6–10.4). Other variables studied,including caries, restorations, and rootcanal treatment, failed to show any significantassociation with tongue cancer.The most recent published study assessingthe association between oral hygiene,periodontal disease, and oropharyngeal andoral cancer was a cross-sectional prospectivecase-control study. 19 In this study, 50 caseswith untreated oral and oropharyngeal squamouscell carcinoma were compared to5,009 cancer-free subjects matched forage and gender. An oral health questionnairewas used to assess tooth brushing as wellas use of mouthrinses, dental floss, andother oral hygiene aids. An oral examinationwas carried out to determine CommunityPeriodontal Index of Treatment Needs(CPITN) scores, missing teeth, caries,restorations, and prostheses, but there was noconsideration given to smoking status or

Chapter 13 Oral Health, Periodontitis, and Cancer 203alcohol consumption. Following very sim -plistic statistical analyses, the authorsreported that advanced perio dontal diseasewas greater in the subjects with oral andoropharyngeal cancer. Up to 76% of thecancer subjects had periodontal probingpockets greater than 6 mm compared to 20%of the patients without cancer. No statisticallysignificant differences could be foundfor caries, missing teeth, restorations, orprostheses.Summary of the RelationshipBetween Oral Health and Oral CancerIt is clear that a number of oral conditions,including tooth loss, poor oral hygiene,poor oral condition, and general periodontalcondition are significant risk factors for oralcancer (Table 1). Due to great variability instatistical analyses, it is difficult to determinethe real significance of many of thesestudies. Nonetheless, several studies havetried to remove confounding influences andhave been able to demonstrate that many ofthese oral conditions remain significant riskfactors. Perhaps the main confounding factorsare smoking and alcohol consumption.When considered together (smoking, alcohol,and oral conditions), risk for oral cancerseemed to increase significantly. When twoof these confounders (smoking and alcohol)were removed, oral conditions remainedhighly significant risk factors. The interplaybetween oral condition and oral cancer,already induced by recognized risk factorssuch as alcohol and tobacco, needs to befurther investigated. It has only been in recentyears that an evaluation of periodontalcondition has been assessed as a potentialrisk factor. While the early data indicate aputative role for periodontal disease, thereis considerable scope for further studies toinvestigate in more detail specific periodontalparameters, as well as types of periodontitisin the periodontal diseases-oral canceraxis.ORAL CONDITIONS ANDVARIOUS TYPeS OF CANCeROral Conditions and UpperGastrointestinal (GI) CancerOne of the first reports to suggest anassociation between oral condition and GIcancer was a case-control study carried outin Germany. 20 The cases included stomachcancer patients (n = 257) and healthy, noncancerouscontrol subjects (n = 766). Informationwas obtained from patient interviewsand 20 variables were found to be significantlyassociated with gastric cancer. Ofthese, early tooth loss was identified as aprominent variable.During the 1990s, several case-controlstudies were conducted to investigate the associationof oral health and upper GI cancer.Demirer et al. 21 studied a Turkish population,principally to investigate the relationshipbetween diet and stomach cancer, but usedsome oral measurements as well. The cancercases (n = 100) had histologically provenadenocarcinoma of the stomach, and age,gender, and residential area-matched subjectswith no gastrointestinal disease were usedas controls (n = 100). Information was obtainedby interview with regard to food andbeverage intake, frequency of tooth brushing,and num ber of missing teeth. In this study,patients with gastric cancer brushed theirteeth less frequently (p < 0.0001) and hadmore missing teeth (p < 0.0001). The relativerisk and confidence intervals for these datawere not reported. A case-control study onChinese populations from three areas inShanxi province (North-Central China) wascarried out to determine the influence of diet,smoking, drinking habits, sociopsychologicalfactors, and family history on the etiologyof esophageal cancer. 22 As part of this study,information concerning dental hygiene habitswas obtained. The cases (n = 326) had beendiagnosed previously with histologicallyconfirmed esophageal cancer and controls

204 Periodontal Disease and Overall Health: A Clinician's Guide(n = 396) were matched by age, gender, andresidence location. Demographic, social, andmedical information was gathered by interviewand included dental hygiene habits. Ofthe parameters evaluated, frequency of toothbrushing was found to be associated withreduced risk for esophageal cancer (OR: 0.2;CI:0.1–0.5). In another case-control study,Watabe et al. 23 studied a Japanese populationto investigate the etiological relation betweengastric cancer and lifestyle. The cases ofgastric cancer (n = 242) and controls (n = 484)were matched for age, gender, and place ofresidence. Oral condition was determinedaccording to number of teeth present. The resultsfrom this study indicated that toothnumber was inversely associated with a highodds ratio for development of gastric cancer.After correcting for some confounders, thenumber of missing teeth was still found to besignificantly associated with gastric cancer.A number of recent case-control, cohort,and cross-sectional studies have beencarried out to ascertain the relationshipbetween oral health and gastric cancer. Ina large case-control study of a Chinesepop ulation, Abnet et al. 24 investigated there lationship between tooth loss and riskof developing esophageal squamous cellcarcinoma, gastric cardiac adenocarcinoma,or gastric noncardiac adenocarcinoma. Thecases had been diagnosed previously throughhistological confirmation of upper gastro -intestinal cancers (n = 2,204). The controls(n = 27,715) were cancer-free, came from theLinxian area of China, and were part of theLinxian General Population Trial cohort in1985. Tooth loss was assessed from subjectinterview and also visual inspection. Toothloss was high in this population with 74% ofparticipants having lost at least one permanenttooth. The median number of teeth lostwas six and median age for first tooth lostwas 39. Further analyses indicated that toothloss was significantly (p < 0.01) associatedwith each of the three cancer sites studied.When assessed for each cancer site, toothloss was associated with a relative risk (RR)of 1.3 (CI:1.1–1.6) in the esophagus, a RR of1.3 (CI:1.0–1.6) for the gastric cardiac, anda RR of 1.8 (CI:1.1–3.0) for the gastric noncardiac.Additional analyses indicated thatthe increased risk was strongest for the firstteeth lost in younger individuals.In a similar study, Abnet et al. 25 carriedout a prospective cohort study to determinewhether tooth loss was associated withincreased risk of gastric noncardiac adeno -carcinoma in a cohort of Finnish smokers.The study population comprised 29,124 subjects,which included 49 esophageal squamouscell carcinomas, 66 esophageal/gastric cardiacadenocarcinomas, and 179 gastric non -cardiac adenocarcinomas. Interviews enabledinformation to be collected on generalbackground characteristics, smoking, anddietary history. The dentition was assessedby interview and related to number of missingteeth. Tooth loss was found to be significantlyassociated with an increased hazardratio (HR) for gastric noncardiac cancer,whereby the HR for edentulous peopleversus those with < 10 teeth lost was 1.65(CI:1.1–2.5). For esophageal squamous cellcarci noma and esophageal/gastric cardiacadeno carcinoma, there were no statisticallysignificant associations with tooth loss.In another cross-sectional study of a ruralChinese population, Wei et al. 26 investigatedthe risk factors for oropharyngealsquamous dysplasia. The study population(Linzhou, formerly Linxian, China) was chosenbecause of a very high prevalence ofesophageal squamous cell carcinoma andgastric cardiac adenocarcinoma. A screeningstudy of 724 adults who were apparentlyhealthy was carried out. An interview wasconducted to obtain general informationon personal characteristics, smoking and alcoholuse, and living conditions. Dental examinationsfollowed the NHANES III protocoland included a tooth count. Of the 720

206 Periodontal Disease and Overall Health: A Clinician's Guide(OR:1.94; CI:1.16–3.26). After a Cox proportionalhazards analysis adjusting for demo -graphic factors, the hazard ratio was deter -mined to be 2.14 (CI:1.30–3.53). With furtheradjustment for socio-economic status, smok -ing status, alcohol consumption, and the intakeof vitamins A and C, the hazard ratio reducedto 1.73 (CI:1.01–2.97). No associationbetween periodontitis and lung cancer wasdetected if the analyses were limited to peoplewho had never smoked. However, if theanalysis was restricted to smokers, then perio -dontitis became significantly associated withlung cancer (HR:1.94; CI:1.14–3.30). Theauthors interpreted these findings to implythat an association between periodontitis andlung cancer, after adjustment for known riskfactors, could be demon strated. However, theycautioned that this periodontitis-cancer associationcould be spurious.The only other published report inwhich periodontitis and lung cancer wasstudied also does not support a link. In thisstudy, associations between tooth loss andmortality patterns in a cohort from Glasgowwere studied 29 in 223 individuals (medianage at baseline was 19) who were followedfor up to 57 years. The cause of death wasrecorded and related to dental data includingmissing teeth, decayed teeth, and restoredteeth. Missing teeth were used as the indexof oral health. Following extensive statisticalanalyses, the authors concluded there wasno association between external causes ofdeath and tooth loss as a continuous (HR:0.97; CI:0.92 –1.03) or categorical variablefor missing five to eight teeth (HR:0.74; CI:0.45–1.21) or missing nine or more teeth(HR:0.89; CI:0.42–1.88). In addition, no evi -dence of an association between lung cancerand tooth loss was found, with or withoutadjustment for smoking.While the literature is scant on thistopic, to date it does not seem to support anyassociation between periodontal conditionand lung cancer.Oral Conditions and Pancreatic CancerIn light of earlier observations that oralhygiene and tooth loss could be associatedwith increased risk for upper GI cancers,Stolzenberg-Solomon et al. 30 hypothesizedthat tooth loss may be associated withpancreatic cancer. This was a cohort studyof Finnish men, ages 50–69, who smokedmore than five cigarettes per day and hadno history of any malignancy apart fromnonmelanoma of the skin or carcinoma insitu. Baseline information obtained by interviewincluded medical, dental (number ofteeth), smoking, and dietary history. Out ofthe 29,104 participants, 174 developed pancreaticcancer. Cox proportional hazard modelswere used to account for age, smoking,education, urban living, and height. In thisstudy, tooth loss, as accounted for by totaledentulism, was associated with pancreaticcancer when compared to individuals missing10 or fewer teeth (HR:1.63; CI:1.09–2.46).However, for people missing 11–31 teeththis association was not significant (HR:1.23;CI:0.82–1.85). The authors concluded thatfurther studies were needed to fully evaluatethe association between tooth loss and pancreaticcancer.Hujoel et al. 28 in their study utilizingthe NHANES I data to investigate the associationbetween periodontitis and variouscancers found no association for pancreaticcancer.A subsequent study by Michaud et al. 2investigated the association of periodontitisin 216 males diagnosed with pancreatic cancerfrom a larger cohort of 48,375 men parti -cipating in the Health Professionals FollowupStudy in the US. The study period was 16years. At baseline, participants reported thenumber of natural teeth and this was updatedevery two years. It was reported that a periodontaldisease analysis was carried out atbaseline and every two years thereafter.However, no details were provided as to thenature of these analyses. Individuals who

Chapter 13 Oral Health, Periodontitis, and Cancer 207were assessed to have periodontal diseaseat baseline had an increased risk of havingpancreatic cancer (RR:1.83; CI:1.36–2.45).When adjusted for age, smoking, profession,race, geographic location, physical activity,diabetes, body mass index, height, cholecystectomy,nonsteroidal anti-inflammatorydrug use, multivitamin use, dietary factors,and total calories, the RR was 1.64 (CI:1.19–2.26). Most of this attenuation could beaccounted for by smoking. The number ofteeth present at baseline was not significantlyassociated with pancreatic cancer. However,in a joint analysis, tooth loss in conjunctionwith periodontal disease resulted in a 2.7-foldincrease (RR:2.71; CI:1.70–4.32) in pancreaticcancer when compared to either noperiodontal disease or no recent tooth loss.Additional analyses indicated that the influenceof periodontal disease was stronger inpeople who had never smoked (RR:2.09;CI:1.18–3.71). Furthermore, the influenceof periodontal disease was also stronger inindividuals with a body mass index of lessthan 25 kg/m 2 (RR:2.2; CI:1.34–3.61). Theauthors concluded that this indicated thatsmoking and obesity were unlikely to explainthe association between periodontaldisease and pancreatic cancer. Nonetheless,they concluded that if the association is to beproven, additional studies are required.In an interesting follow-up to theMichaud et al. 2 publication, Taguchi, 31 ina “Letter to the Editor,” commented thatMichaud and colleagues did not adjust forthe effects of passive exposure to cigarettesmoke, which could have negated their findings.In addition, Taguchi suggested that tobetter understand the relationship betweenperiodontal disease and pancreatic cancer,it would be helpful to demonstrate an associationbetween duration and grade of periodontal disease and pancreatic cancer risk. Inresponse to these comments Michaud et al. 2argued that not withstanding the lack of dataconcerning environmental tobacco smoke,controlling for passive smoking in theirstudy may have attenuated their findings butnot eliminated the association between periodontaldisease and pancreatic cancer. It wasnoted that the two-fold increase in risk forpancreatic cancer in people with periodontaldisease who had never smoked is greaterthan the reported association between passivesmoking and pancreatic cancer. Furthermore,it was pointed out this two-foldincrease in risk for pancreatic cancer amongpatients with periodontal disease who hadnever smoked is of a similar magnitude tothe association between current smoking andpancreatic cancer. With regard to the need forassessment of duration and severity of periodontaldisease, Michaud was in agreement.Indeed, this should be a requirement for allfuture studies investigating the associationbetween periodontal disease and any cancer.PeRIODONTAL DISeASe,CANCeR, AND MORTALITYTo date, very few studies have investigatedthe association between periodontaldisease and cancer by assessment of the clinicalparameters of periodontal status. By far,the majority of studies have reported on theassociation between tooth loss and cancerrisk. Such approaches may be flawed sincetooth loss may also result from trauma or,more commonly, caries. However, thesestudies claim that because teeth lost at anolder age are more likely due to periodontaldisease compared to those lost at younger ages(which may be due more to dental caries),tooth loss in older individuals can be a goodsurrogate marker of periodontal disease. Onthe basis of that, it seems assessment of toothloss may provide an insight into the overallrole of oral health and its effect on cancerrisk. The cumulative influence of age ontooth loss and its relationship to periodontaldisease can be seen in the study by Michaud,et al. 2 In this study, which ran more than 16years, the number of teeth lost at baseline

Chapter 13 Oral Health, Periodontitis, and Cancer 209outcomes were studied as well as total death,upper GI cancer death, other cancer death,heart disease death, and fatal stroke. It wasfound that individuals with greater than theage-specific median number of teeth lost hadstatistically increased risk of total death (RR:1.13; CI:1.09–1.18) and death from upper GIcancer (RR:1.35; CI:1.14–1.59). After accountingfor the confounding effect of smoking,these associations were generally stillsignificant. Risk from death at other cancersites showed no significant associations withtooth loss. It was concluded that tooth losswas significantly associated with increasedrisk for total death from cancer and from upperGI cancer.In contrast to the above findings, Cabreraet al., 33 in a study investigating the relationshipbetween tooth loss and chronic disease, foundno associations between tooth loss and totalcancer mortality after adjusting for knownconfounders (RR:1.16; CI:0.90–1.49). Thiswas a prospective study of females residing inGothenburg, Sweden over 24 years. The dentalexamination consisted of determining toothnumber; mortality outcomes were death fromcardiovascular disease and all-site cancer.Despite no association between tooth numberand all-site cancer mortality, no assessmentof site- specific cancers was made. Similarfindings were noted by Tu et al. 29 in thepreviously described Glasgow cohort study.Moreover, after adjusting for a variety of con -founders, no association was found betweenall-cause mortality for each additional missingtooth (HR:1.01; CI:1.00–1.02) or cancermortality (HR:1.00; CI: 0.98–1.02). From thisstudy, it appeared that any relationshipbetween tooth loss and cancer mortality couldbe explained by other causal or confoundingmechanisms.Tramini et al. 34 investigated tooth loss andassociated factors in elderly patients in Francewho had been institutionalized long term. Thiswas a cross-sectional study of 321 elderlypatients in which socio-economic, behavioral,medical, and oral information was recorded.Multivariate logistic regression analyses werecarried out to test the associations betweenthese covariates and tooth loss. The resultsindicated that “cancerous disease” was themost significant condition associated withpartial tooth loss. The type of “cancerousdisease” was not qualified. From these data,the authors concluded that the number ofremaining teeth has a strong effect on oralhealth-related quality of life.Söder et al. 35 published the results froma 16-year longitudinal study investigatingperiodontitis and premature death. In thisstudy the causes of death for 3,273 individualswere recorded and subsequently relatedto dental findings. The dental assessment atbaseline included recording missing teeth,gingival inflammation, oral hygiene status,calculus scores, and periodontal probingpocket depth. An individual was consideredto have periodontitis if he or she had at leastone tooth with a probing pocket depth of 5mm or greater. After logistic relation analysisof being dead (dependent variable) andseveral independent variables including age,gender, education, income, smoking, dentalvisits, dental plaque, gingival inflammation,missing teeth, and missing molars, the totalnumber of individuals who died from neoplasmswas significantly higher in the perio -dontitis group who had missing molar teeth(OR:3.62; CI:1.28–10.16). It was concludedthat young periodontitis patients with missingmolars were at higher risk for prematuredeath by neoplasm than their more healthycounterparts.In another case-control study, Hiraki etal. 36 examined the relationship between toothloss and the risk of 14 types of cancers ina Japanese population. The cohort consistedof 5,240 cancer subjects and 10,480 noncancercontrols who were age- and gendermatched.Information on lifestyle, smoking,alcohol consumption, diet, exercise, andnumber of teeth present was collected. Of the

210 Periodontal Disease and Overall Health: A Clinician's Guide14 cancers studied, tooth loss was found tobe associated with esophageal (OR:2.36;CI:1.17–4.75) and lung cancer (OR:1.54;CI:1.05–2.27). After adjusting for age, theseassociations remained significant but weredecreased. These findings are in agreementwith the more focused studies on upper GIcancer and lung cancer.In a detailed study, Michaud et al. 37analyzed periodontal disease, tooth loss, andcancer risk in a male health professional cohort.This prospective study was carried outon the same Health Professionals FollowupStudy as described in the above section onpancreatic cancer. Commenced in 1986,51,529 (97% male) participants answered aquestionnaire on lifestyle, smoking history,alcohol consumption, physical activity, diet,and medical history. Follow-up questionnaireswere completed every two years until2002. Dental assessments were also carriedout and these consisted of self-reported experienceof periodontal disease and toothloss. Cancer experience was recorded by theparticipants who were required to report anynew cancer diagnosis on the biennial questionnaires.The data were analyzed and multivariatehazards ratios and 95% confidenceintervals were calculated by Cox proportionalhazard models for periodontal diseaseexperience and number of missing teeth atthe baseline measurement. From this study,the five main cancers experienced by thiscohort were colorectal, melanoma of theskin, lung, bladder, and prostate. Followingadjustment for known cancer risk factorssuch as smoking history and diet, comparedto individuals with no reported history ofperiodontal disease, individuals with a selfreportedhistory of periodontal diseasedemonstrated an increased risk for totalcancer (HR:1.14; CI:1.07–1.22). For specificcancers, a past history of periodontal diseasewas associated with increased risk for lung(HR:1.36; CI:1.15–1.60), kidney (HR:1.49;CI:1.12–1.97), pancreas (HR:1.54; CI:1.16–2.04) and hematological cancers (HR:1.30;CI:1.11–1.53). These findings for lung andpancreas were in agreement with previouslypublished studies. The findings for kidneyand hematological cancers were new andhave not been reported previously. In contrastto previous studies, the association foresophageal cancer, while increased, was notsignificant after adjusting for smoking status.Missing teeth, which was also noted to beassociated with smoking status, was foundto be associated with increased risk forlung cancer only (HR:1.7; CI:1.37–2.11).The associations were strongest for periodontaldisease and missing teeth whensmoking was not considered a covariate; thisindicates that smoking was a strong confounderfor these associations. Interestingly,for pancreatic and kidney cancers, the associationsremained strong even after controllingfor smoking. For lung cancer, smokingwas found to be a very strong confounderand was probably largely responsible for riskof this cancer. Removal of confounding factorsfor kidney and pancreatic cancers suchas diabetes and obesity did not significantlychange the associations, indicating that thesetwo known risk factors were not likely tobe responsible for the noted association ofperio dontal disease with pancreatic and kidneycancers. Overall, the authors concludedthat periodontal disease appeared to be associatedwith a small but nonetheless significantrisk for cancer in general. Some influenceof smoking was noted in smokersbut the associations persisted in people whohad never smoked. Whether some of theseassociations were due to direct effects of periodontaldisease on cancer or the result ofbeing more like a surrogate marker requiresfurther investigation.PeRIODONTITIS, VIRUSeS,AND ORAL CANCeRIn recent years, several reports havesuggested that viruses may be associated

Chapter 13 Oral Health, Periodontitis, and Cancer 211with various forms of periodontitis. In particular,Epstein-Barr Virus (EBV) has beenimplicated in the pathogenesis of advancedand aggressive forms of periodontitis. 38 Ithas been hypothesized that EBV proteinsmay lead to an up-regulation of growthfactors and cytokines involved in celltransformation of EBV-associated oralmalig nancies. 39 While this is an interestingtheory, considerably more research isneeded to determine the exact role, if any,that viruses play in periodontitis and oralmalignancies.ORAL CONDITIONS, Helicobacterpylori, AND CANCeRHelicobacter pylori is associated withchronic gastritis, duodenal ulcers, and increasedrisk of developing gastric adenocarcinoma.40,41 Since H. pylori can be isolated inthe oral cavity, especially in individuals withperiodontitis who have the bacterium in theirgastrointestinal tract, 42 it has been proposedthat the oral cavity may act as a reservoir forH. pylori-associated gastric cancer. While ithas been suggested that H. pylori cannot survivein the oral cavity, there are studies thatsupport the notion that H. pylori can be foundin dental plaque and periodontal pockets. 43,44Nonetheless, it is generally accepted that thepresence of H. pylori in the oral cavity maybe independent of infection status of thestomach 45 and no good evidence exists forthe presence of periodontal disease, oralH. pylori, and gastric cancer. 30POSSIBLe MeCHANISMS FOR THeReLATIONSHIP BeTweeN ORALCONDITIONS AND CANCeRA number of hypotheses have been proposedto explain the observed relationshipsbetween periodontal disease and cancerincluding poor diet, mechanical irritation,chronic infection, systemic inflammation,and immune suppression, as well as increasedexposure to carcinogens. 1,32Diet and Mechanical IrritationThe role of poor oral condition andtooth loss with trauma has been well discussedfor both oral and upper gastroin -testinal cancer. For decades, an associationbetween poor restorative dentistry and illfittingprostheses and oral cancer has beenrecognized. 46 However, more recently it hasbeen proposed that tooth loss may alter dietarypatterns and this may be a contributoryfactor to the development of upper GI cancer.32 In addition, it has been suggested thattooth loss may result in inadequate masticationand the resulting poorly chewed foodbolus could have an irritating effect on theesophagus, leading to increased risk of cancerthrough mechanical irritation. 47 To datethese hypotheses have not been proven. Inlight of findings that tooth loss and chewingefficiency are not related and that tooth lossis associated with increased risk for GIcancer, the fact that the GI system is a sitethat is unlikely to be affected by food bolussize mitigates against mechanical-traumahypotheses. 32InflammationInflammation appears to play an importantrole in carcinogenesis and the presenceof inflammation may enhance cellularproliferation and mutagenesis, reduce adapta -tion to oxidative stress, promote angiogenesis,inhibit apoptosis, and increase secretion ofinflammatory mediators. 48 This is demon -strated with chronic pancreatitis being associatedwith an increased risk of pancreaticcancer. 49 Indeed, inflammation has beenshown, at least in animal studies, to be associatedwith the progression of liver and coloncancer. 50 Since periodontal disease is aninflammatory disease in which there areelevated levels of circulating inflammatorycytokines, a suggestion has been made thatthis could be a plausible link leading to thebreakdown of normal cell growth controland potential carcinogenesis. 1 Thus, the host

212 Periodontal Disease and Overall Health: A Clinician's Guideresponse in periodontal disease may lead to asystemic exposure to pro-inflammatory cyto -kines, which in turn may lead to increasedrisk of neoplastic transformation at distantsites. However, the situation may not be assimple as this since most studies investigatingthe link between cancer and inflammationconsider the effect of local inflammationat the site of the cancer rather than systemicelevation of inflammatory mediators. Whileit is possible that elevated systemic levels ofinflammatory cytokines may encourage subthresholdneoplastic states to become neoplastic,local inflammation and local releaseof inflammatory mediators at a site of potentialneoplastic transformation seems morelikely. Alternatively, it has been suggestedthat individuals who suffer from both periodontaldisease and cancer may share similargene polymorphisms in genes encodinginflammatory cytokines; thus periodontitismay merely be a marker of an underlying geneticpredisposing factor rather than a truerisk factor for cancer.InfectionChronic infections have been associatedwith increased cancer risk. For example,bacterial infections such as H. pylori havebeen implicated in gastric cancer as well asHepatitis B and C viral infections implicatedin hepatocellular carcinoma. 40,41Since periodontitis is a chronic infection,it has been postulated that periodontalbacteria within the subgingival plaquebiofilm may be associated with carcinogenesisthrough the release of a multitude oftoxic products (endotoxins, enzymes, hydrogensulfide, ammonia) leading to cell mutationsin tumor suppressor genes and protooncogenesor alter signaling pathways thataffect cell proliferation or cell survival. 18 Inaddition, chronic inflammation induced byperiodontal pathogens results in chronic releaseof pro-inflammatory cytokines, chemo -kines, prostaglandins, growth factors, andenzymes that may have indirect effects oncarcinogenesis by deregulating physiologicalcell turnover and cell growth.In another hypothesis, it has been proposedthat periodontal pathogens may increasethe level of certain carcinogens such asnitrosamines. 32 The formation of endogenousnitrosamines in the oral cavity by nitratereducingbacteria is promoted by poor oralhygiene as well as by tobacco use and certaindietary factors. 51 Increased production of carcinogenicnitrosamines by oral bacteria hasbeen suggested as a possible mechanism foran increased risk of pancreatic cancer in individualswith reported periodontal disease. 2ImmunityPeriodontitis in susceptible patientsmay reflect a failure in the interaction betweenthe innate and adaptive immune responseto clear the bacterial challenge withinthe periodontal pocket. Deregulation of theimmune response may also place an individualat risk of inadequate cellular surveillancefor tumor growth. In particular, thestable periodontal lesion consists of a predominantlyT helper cell 1 (Th l) response 52and is associated with high levels of interferon-(IFN-), an important cytokine incell-mediated immunity and tumor surveillance.53 The progressive periodontitis lesionconsists predominantly of a Th 2 responsewith lower levels of IFN- and a poor innateimmune response. 52 Hence, periodontitis couldmerely be a marker of immune dysfunctionrather than a true risk factor for cancer.CONCLUSIONTo date, only a limited number of studieshave investigated the association betweenperiodontal disease and cancer risk, althoughmany reports have been published concerningthe association between cancer risk andoral condition, oral hygiene, and tooth loss.Positive associations have been demonstratedeven after controlling for known risk factors

Chapter 13 Oral Health, Periodontitis, and Cancer 213such as smoking or when analyses are restrictedto nonsmokers. However, these findingsneed to be interpreted with caution asthere may be additional confounding factorsthat researchers are unaware of and that havenot been included in the analyses for adjustment.There is a need for more studies ofappropriate statistical power using appropriatemarkers for periodontal disease, appropriateconsideration of the different types ofperiodontal disease, as well as the appropriateconsideration of confounding factors.Supplemental ReadingsMeyer MS, Joshipura KJ, Giovannucci E, Michaud DS.A review of the relationship between tooth loss, periodontaldisease and cancer. Cancer Causes Control2008;19:895–907.Michaud DS, Joshipura K, Giovannucci E, Fuchs CS. Aprospective studyof periodontal disease and pancreaticcancer in US male health professionals. J Nat CancerInst 2007;17:171–175.Hujoel PP, Drangsholt M, Spiekerman C, Weiss NS.An exploration of the periodontitis-cancer association.Ann Epidemiol 2003;13:312–316.Michaud DS, Liu Y, Meyer M, Giovannucci E, JoshipuraK. Periodontal disease, tooth loss, and cancerrisk in male health professionals: A prospective cohortstudy. Lancet Oncol 2008;9:550–558.Coussens LM, Werb Z. Inflammation and cancer. Nature2002;420:860-867.Karin M, Greten FR. NF-Kappaβ: linking inflammationand immunity to cancer development and progression.Nat Rev Immunol 2005;5:749–759.ReFeReNCeS1. Meyer MS, Joshipura KJ, Giovannucci E, MichaudDS. A review of the relationship between toothloss, periodontal disease and cancer. Cancer CausesControl 2008;19:895–907.2. Michaud DS, Joshipura K, Giovannucci E, FuchsCS. A prospective study of periodontal disease andpancreatic cancer in US male health professionals.J Nat Cancer Inst 2007;17:171–175.3. Wynder EL, Bross IJ, Feldman RM. A study of theetiological factors in cancer of the mouth. Cancer1957;10:1300–1323.4. Graham S, Dayal H, Rohrer T, Swanson M, Sultz H,Shedd D, Fischman S. Dentition, diet, tobacco, andalcohol in the epidemiology of oral cancer. J NatlCancer Inst 1977;59:1611–1618.5. Zheng TZ, Boyle P, Hu HF, Duan J, Jian PJ, Ma DQ,Shui LP, Niu SR, Scully C, MacMahon B. Dentition,oral hygiene, and risk of oral cancer: A casecontrolstudy in Beijing, People’s Republic ofChina. Cancer Causes Control 1990;1:235–241.6. Winn DM, Blot WJ, McLaughlin JK, Austin DF,Greenberg RS, Preston-Martin S, Schoenberg JB,Fraumeni JF Jr. Mouthwash use and oral conditionsin the risk of oral and pharyngeal cancer. CancerRes 1991;51:3044–3047.7. Marshall JR, Graham S, Haughey BP, Shedd D,O’Shea R, Brasure J, Wilkinson GS, West D.Smoking, alcohol, dentition and diet in the epidemi -ology of oral cancer. Eur J Cancer. Part B. OralOncology 1992;28B:9–15.8. Bundgaard T, Wildt J, Frydenberg M, Elbrønd O,Nielsen JE. Case-control study of squamous cellcancer of the oral cavity in Denmark. CancerCauses Control 1995;6:57–67.9. Schildt EB, Eriksson M, Hardell L, Magnuson A.Oral infections and dental factors in relation to oralcancer: a Swedish case-control study. Eur J CancerPrev 1998;7:201–206.10. Velly AM, Franco EL, Schlecht N, Pintos J,Kowalski LP, Oliveira BV, Curado MP. Relationshipbetween dental factors and risk of upper aero -digestive tract cancer. Oral Oncol 1998;34:284–291.11. Talamini R, Vaccarella S, Barbone F, Tavani A, LaVecchia C, Herrero R, Muñoz N, Franceschi S.Oral hygiene, dentition, sexual habits and risk oforal cancer. Br J Cancer 2000;83:1238–1242.12. Moreno-López LA, Esparza-Gómez GC, González-Navarro A, Cerero-Lapiedra R, González-HernándezMJ, Domínguez-Rojas V. Risk of oral cancer associatedwith tobacco smoking, alcoholconsumption and oral hygiene: a case-control studyin Madrid, Spain. Oral Oncol 2000;36:170–174.13. Garrote LF, Herrero R, Reyes RM, Vaccarella S,Anta JL, Ferbeye L, Muñoz, N, Franceschi S. Riskfactors for cancer of the oral cavity and oro-pharynxin Cuba. Br J Cancer 2001;85:46–54.14. Balaram P, Sridhar H, Rajkumar T, Vaccarella S,Herrero R, Nandakumar A, Ravichandran K, RamdasK, Sankaranarayanan R, Gajalakshmi V, MuñozN, Franceschi S. Oral cancer in southern India: theinfluence of smoking, drinking, paan-chewing andoral hygiene. Int J Cancer 2002;98:440–445.15. Lissowska J, Pilarska A, Pilarski P, Samolczyk-Wanyura D, Piekarczyk J, Bardin-Mikollajczak A,Zatonski W, Herrero R, Muñoz N, Franceschi S.Smoking, alcohol, diet, dentition and sexual practicesin the epidemiology of oral cancer in Poland.Eur J Cancer Prev 2003;12:25–33.

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CHAPTER 17Dental and Medical Comanagementof Osteoporosis, Kidney Disease,and CancerDawn J. Caster, John H. Loughran, Denis F. KinaneINTRODUCTIONBefore addressing any therapeutic management,it needs to be determined whetheror not there are indeed associations, mechanisticlinks, or shared risk factors for dentaldiseases and osteoporosis, kidney disease,and cancer. Fortunately, these are addressedin previous chapters; the goal of this chapteris to consider the management issues thatmay arise in dealing with the comorbid state.Can we modify treatment? Do we need toprescribe the routine drugs or are there alternatives?How should the dentist or physicianmanage these patients presenting withboth oral and systemic conditions? First weneed to consider the diseases and the characteristicsthat might complicate their dualmanagement. Each section concludes withsuggestions for both the physician and dentistfor treating these patients.OSTEOPOROSIS ANDOTHER BONE DISEASESOsteoporosisOsteoporosis is the most common bonedisease in humans. Disease prevalence hasbeen reported by some sources as 3% to6% in men and up to 13% to 18% in women(approximately 8 million women and 2 millionmen), with a significantly higher prevalencereported for those meeting diagnosticcriteria for osteopenia. 1 The risk of devel -oping osteoporosis increases with age, es -pecially in women, due to loss of ovarianfunction that precipitates rapid bone loss. 2Approximately 300,000 hip fractures occureach year requiring hospital admission and,ultimately, surgical correction. 2 Consideringthe increasing size of the elderly populationas the “baby boomers” rapidly approach theirsixth and seventh decades of life, it is easy tosee how this disease process can and willaffect the healthcare system of the UnitedStates and worldwide.Osteoporosis is diagnosed on the basisof a low-impact or fragility fracture or lowbone mineral density (BMD), which is bestassessed by central dual-energy x-ray ab -sorp tiometry (DEXA). 3 By World HealthOrganization guidelines, a diagnosis of osteoporosisis made by DEXA scan demonstrationof a BMD which is 2.5 standard deviationsbelow the young adult referencemean based on gender. Classifications forosteoporosis are broken down into primaryand secondary etiologies. Secondary causesof osteoporosis are many, and although theyare less commonly seen in clinical practice,there are a few, such as diabetes mellitus andchronic obstructive pulmonary disease, thatare seen quite often in osteoporosis patients.Paget’s DiseasePaget’s disease is a disorder characterizedby excessive resorption of bone. Subsequentto this resorption, new bone is depositedin a haphazard fashion to compensatefor the rapid bone loss. This creates the “mosaic”pattern commonly associated with thedisease process that describes the disorganizedtrabecular bone formed instead of the

CHAPTER 17 Dental and Medical Comanagement of Osteoporosis,CHAPTER 17 Kidney Disease, and Cancer 271normal pattern of lamellar bone. This disorderedbone deposition is weak and prone todeformities as well as fracture. Incidence ofPaget’s disease is not well reported, and thecurrent incidence of 3.0% to 3.7% is basedon autopsies and radiographs of patients over40 years of age. 4 Etiology of the disease isunknown, although there are several proposedtheories, including viral and genetic factors.Careful evaluation of history and physicalexamination help to delineate Paget’s diseasefrom other possible diagnoses (e.g.,metastatic bone disease). Certain serologicaland radiographic tests aid in making thediagnosis. Although there are several clinicalmanifestations of the disease including complaintsof upper dentures not fitting anymore,it is the skeletal sequelae that are most germaneto the current discussion.Metastatic Bone DiseaseMetastatic bone disease is most commonlyassociated with breast and prostate cancer,but is frequently seen in many advancedcases of malignancy. Tumor cells express severalchemical and genetic factors that makebone a preferred site for localization andgrowth. There is much discussion in the medicalliterature regarding the propensity of certainmalignancies to express osteoblastic versusosteolytic bone lesions. However, mostpatients with bone metastases have evidence ofboth lesions. Clinical manifestations of meta -static bone disease include pain, fracture, andpossibly spinal cord compression. Cord compressionis a medical emergency requiring immediateintervention to avoid permanent neurologicaldysfunction. Although antineoplasticand analgesic therapies are the mainstay oftreatment for most metastatic bone lesions,there are alter native strategies that have beengaining favor, such as bisphosphonate therapy.Pharmacology of the BisphosphonatesBisphosphonates are synthetic analoguesof inorganic pyrophosphate. Theywere initially developed in the 1800s andhave industrial uses such as softening waterfor irrigation systems. The compound’s abilityto soften water is due to the inhibition ofcalcium carbonate crystal formation, and itwas later found that bisphosphonates canalso inhibit calcium pyrophosphate crystalformation. Bisphosphonates are classifiedinto two groups based on whether or not theycontain an amino group. Mechanism of actiondiffers between the groups. Aminobisphosphonates(zolendronate, alendronate,pamidronate, ibandronate, and risedronate)disrupt the pathway involving metabolismof mevalonic acid. They also promoteabnormalities in cytoskeleton production,inducing apoptosis of osteoclasts that retardbone resorption. Bisphosphonates thatdo not contain amino groups (etidronate,clodronate, and tiludronate) act by disruptingATP formation after being metabolizedwithin osteoclasts, also promoting apoptosis.There is, unfortunately, a secondary effectthat bisphosphonates exhibit—that is, theirability to inhibit bone mineralization, therebycausing osteomalacia. Once again we seea difference among the classes. Whereasetidronate has been shown to inhibit resorptionand mineralization at similar concentrations,alendronate has been shown tohave a markedly favorable therapeutic index(i.e., better resorption inhibition thandefective mineralization) up to 36 monthsfrom the initiation of therapy. 5 The overallhigher potency and lower toxicity of aminobisphosphonates are likely the reasons theyare used more often in clinical practice thanother bisphosphonates.Although less than 10% of orally ingesteddoses of bisphosphonates are absorbed,between 20% and 50% of the absorbeddose accumulates in bone dependingon the rate of bone turnover. The remainderof the dose is excreted in urine. The half-lifeof these drugs varies considerably, but in thecase of alendronate (one of the more common

272 Periodontal Disease and Overall Health: A Clinician's Guidepharmaceutical agents used in the treatmentof disorders of bone metabolism), it is as longas 10 years. One point of contention is thetimeframe for which the compound persistswithin the bone, which according to somesources can be the lifetime of the patient. 6This is an important factor to bear in mindwhen considering interruption of therapyprior to surgical procedures.Osteonecrosis of the JawOsteonecrosis of the jaw (ONJ) has attractedincreased interest for both medicaland dental practitioners in recent years. Inthe early part of the last century, the term“phossy jaw” had been utilized to describethe condition that linked white phosphorusexposure with the disease process of osteonecrosis.Radiation and chemotherapyhave also been implicated as possible etiologiesof ONJ. The most recent debate in thecurrent literature and to be addressed in thischapter is bisphosphonate-associated ONJ.Bisphosphonates have taken on a vital role inthe management of chronic disease processessuch as osteoporosis and Paget’s disease, aswell as the prevention of skeletal complicationsin patients with bone metastases. Bisphosphonate-associatedONJ was first reportedin 2003, and since then many morecases have come to light, propelling theAmerican Society for Bone and Mineral Research(ASBMR) to appoint a task force toreview the literature and make recommendationsfor future diagnosis and management.The case definition of bisphosphonateassociatedONJ is an area of exposed bone inthe maxillofacial region that does not healwithin eight weeks after identification by ahealthcare provider, in a patient who was receivingor had been exposed to a bisphosphonateand had not had radiation therapy tothe craniofacial region. 7 The reporting ofmany cases involving ONJ associated withbisphosphonate use was made prior to theaccepted ASBMR task force definition.Therefore, the quality of evidence regardingthe true incidence of ONJ is in question,as is the true causal relationship betweenbisphosphonates and ONJ. Information presentedhere is based on the most current facts,but this is an expanding field and the readershould update regularly on this topic.The known epidemiologic data for bisphosphonate-associatedONJ varies greatlybased on the disease processes for which thedrug is utilized (Figures 1-3). Therefore, thischapter will consider the osteoporosis andPaget’s disease patient subsets and those receivingbisphosphonates for skeletal compli -Figure 1. Clinical Photograph of anFigure 1. Upper Jaw Exhibiting MarkedFigure 1. Osteonecrosis in a Patient onFigure 1. Bisphosphonate TherapyCourtesy of Dr. George M. Kushner, University ofLouisville Dental School.Figure 2. Orthopantomograph ofFigure 1. Osteonecrosis in the LowerFigure 1. Border of the Lower JawCourtesy of Dr. George M. Kushner, University ofLouisville Dental School.

CHAPTER 17 Dental and Medical Comanagement of Osteoporosis,CHAPTER 17 Kidney Disease, and Cancer 273Figure 3. Computer-Assisted TomographicFigure 1. View of the Same Subject SeenFigure 1. in Figure 2 DemonstratingFigure 1. Extensive Osteonecrosis of theFigure 1. Lower Border of the Lower JawCourtesy of Dr. George M. Kushner, University ofLouisville Dental School.cations of malignancy as separate entities.Patients receiving bisphosphonate therapy forosteoporosis and Paget’s disease are mostlytreated with oral agents, whereas those withmalignancy complications generally receiveintravenous therapy. There is conflictingevidence regarding the incidence of ONJ inpatients receiving bisphosphonates for osteo -porosis. One study estimated the prevalenceto be < 1 in 250,000. 8 The incidence of ONJin patients receiving bisphosphonate therapyfor complications of malignancy rangesbetween 1% and 10%. 9 A prospective studyby Bamias and colleagues of cancer patientsreceiving bisphosphonate therapy estimatedthat the risk of developing ONJ increasedwith length of exposure to the drug and wasdependent on the bisphosphonate used. Althoughthe data supporting these claims arelimited, it is generally accepted that the riskof developing ONJ is higher in patients receivingtreatment for metastatic bone disease.Whether or not these higher incidencerates are secondary to the higher doses receivedby patients with malignancy comparedto those receiving therapy for osteoporosisor Paget’s disease remains to be seen.The pathogenesis of ONJ remains unknown.Patients with the aforementioneddisease processes requiring bisphosphonatetherapy have many areas of poor bonehealth. These areas are posited to be at highrisk for developing ONJ. The antiangiogeniceffects attributed to bisphosphonates are purportedto leave areas such as these in a relativelyischemic condition. Ischemic regionswith infarcted bone will not properly remodelbecause of the antiresorptive propertiesof these medications. Areas such as theseare susceptible to further necrosis aftertrauma such as oral surgery. Furthermore,these areas are a perfect nidus for infectionand a wide range of bacterial infections isfound in these situations. Once again, theseare only proposed mechanisms and furtherclinical research is necessary to elicit thepathophysiology of the disorder, particularlyregarding the issue of predisposing factorssuch as corticosteroid use or alcohol abuse.A currently investigated topic is theearly identification of osteonecrotic boneprior to initiation of bisphosphonate therapyor oral surgery. This is extremely difficult,however, as most readily available radiographictechniques cannot identify defectsof cancellous bone until advanced stages.Current recommendations by the task forcecall for development of noninvasive diagnosticand imaging techniques to furthercharacterize the disorder.ManagementConditions requiring bisphosphonatetherapy are common and may (especially osteoporosis)become more prevalent in thenear future. Morbidity secondary to diseaseprogression such as ONJ negatively impactsthe healthcare system financially, and hasconsiderable emotional and physical ramificationsfor patients. Thus, ongoing preventivemeasures are necessary in the managementof these medical conditions. Until more effectivetherapies with fewer adverse effects

274 Periodontal Disease and Overall Health: A Clinician's Guideare available, the use of bisphosphonateswill continue. The heightened awareness ofONJ associated with these medications, combinedwith stronger guidelines outlining casedefinitions and a call to responsible reporting,has already resulted in an increased numberof cases reported over the past two years.Management of bisphosphonate-associatedONJ will require an interdisciplinary approach,with open communication betweenmedical and dental practitioners and patientsalike. Since the incidence and risks of developingthis complication are different betweenpatient subsets, this chapter will outlinethe recommended management strategiesseparately for patients with osteoporosis/Paget’s disease versus those treated for complicationsof malignancy. These recommendationsfor management are adapted fromthe guidelines of the 2007 ASBMR TaskForce. 7As previously mentioned, free communicationbetween medical and dental practitionersis necessary to ensure proper continuityof care. Full disclosure concerning therisks and benefits of medical therapy is theresponsibility of the medical practitioner forany patients initiating treatment with bisphosphonates.Reducing the risk of developingONJ includes observing strict maintenanceof the patient’s oral hygiene andregular follow-ups with a dental practitioner,which should be an integral part of the medicalcare for all patients taking bisphosphonates.Patients are to be instructed that anyoral problems should be reported to theirphysician and dentist promptly.As previously discussed, the risk of developingONJ for patients receiving oraltherapy for osteoporosis or Paget’s disease isfairly low. The risk also seems to be relatedto length of exposure to the medication.Therefore, it is not necessary to have a dentalevaluation prior to the initiation of bisphosphonatetherapy for these disorders. Forpatients taking these medications longer thanthree years, there are more detailed recommendationsfor management. Patients onlong-term therapy should receive appropriatenonsurgical treatment for periodontal disease(unless contraindicated by comorbid illness).Moderate bone recontouring is accep -table if necessary. There is currently nocontraindication to dental implant surgeryin this patient subset. Endodontic treatmentis the preferred mode of therapy over extrac -tion when at all possible. When invasive therapyis necessary, it is recommended to temporarilydiscontinue bisphosphonate therapy;however, there is no evidence to support improveddental outcomes when discontinuingtherapy. Also as previously mentioned, thelong half-life of certain bisphosphonates andthe even longer retention of the medicationin bone call into question the validity ofsuch strategies. Once again, quality communicationamong practitioners and patientsis of the utmost importance in making thesedecisions.For patients receiving medical therapyfor complications of malignancy, the risks ofdeveloping ONJ are greater, and thus managementstrategies are more conservative.Dental evaluation by a qualified specialistshould be completed prior to the initiation oftherapy, with follow-up evaluations at 6- to12-month intervals. If at all possible, invasiveprocedures with appropriate time allottedfor healing should be performed prior tothe start of medical therapy. If medical therapymust be initiated sooner, then concomitantsurgical treatment is recommended withclose follow-up. Elective procedures suchas implant placement and extraction ofasymptomatic teeth are not recommended.Symptomatic teeth should be treated by nonsurgicalmeans when possible, unless thetooth is excessively mobile and presents arisk for aspiration.Patients with established ONJ shouldbe referred to a qualified dental practitionerfor management. For those with clinical

CHAPTER 17 Dental and Medical Comanagement of Osteoporosis,CHAPTER 17 Kidney Disease, and Cancer 275evidence of infection, appropriate antimicrobialtherapy is recommended. Surgicalintervention for ONJ should be delayed unlessthe necrotic bone has sharp edges thatmay cause continued trauma to adjacent softtissues. Segmental jaw resection may be necessaryfor large areas of necrosis. The decisionto discontinue bisphosphonate therapy forthose with this complication will depend onthe patient’s clinical condition, as this strategyhas not been established to improveoutcome. Recommendations are to ensuremaintenance of a high standard of oralhygiene, and ensure no active disease byemploying nonsurgical and surgical therapywhere needed, as well as adjunctive anti -microbial therapy. Anti-inflammatory drugsshould be avoided unless there is evidencefrom research that such medications will notinterfere or interact with medications usedfor osteoporosis. There is a possibility thatany dampening of normal inflammation maypermit the bacteria in an infectious lesion tobecome more virulent, allowing greater destructionof bone. Alternatively, dampeninginflammation may be helpful in certain casesof periodontal disease, but until there is evidenceone way or the other, anti-inflammatorydrugs should be avoided in this comorbidsituation.KIDNEY DISEASEThe number of patients with chronickidney disease (CKD) is growing and is projectedto rise in the future. As the incidenceclimbs, patients with CKD, including thosewith end-stage renal disease (ESRD), willrepresent a larger portion of those seekingdental treatment. With this in mind, itis important to understand the complexinteraction between CKD and periodontaldisease.CKD is associated with many physiologicchanges that might contribute to thedevelopment of periodontal disease. Thereare several documented physiologic changesin oral tissues that have been associated withCKD. These include xerostomia, decreasedsalivary pH levels, decreased mineralization,and loss of the lamina dura. 10 Additionally,some of the medications commonly prescribedto CKD patients may increase therisk of developing periodontal disease.Both CKD and periodontal disease havebeen implicated as sources of chronic inflammation.Thus, periodontal disease mayrepresent a modifiable contributor to thealready high inflammatory burden in patientswith CKD, especially in those withdiabetes. Treatment of periodontal diseasein these patients could decrease the overallchronic inflammatory burden and its sequelae.A collaborative effort between dentaland medical professionals is necessary toensure that patients get appropriate adviceand treatment.Overview of Kidney FunctionThe principle function of the kidneys isto remove waste products of metabolism, aswell as maintain fluid and electrolyte balance.The kidneys also play a vital role inblood pressure regulation through the releaseof renin. Erythropoietin, a potent stimulatorof red blood cell production, is also madeby the kidneys. Additionally, the kidneysplay an important role in bone health by providingthe final step in the conversion of vitaminD to its active form. Decreased kidneyfunction can affect each of these areas andhas far-reaching consequences on overallhealth.The waste products removed by the kidneyinclude blood urea nitrogen, a by-productof protein metabolism, and creatinine, a byproductof muscle breakdown. Blood levelsof these compounds are commonly used inlab testing to measure kidney function. Morethan 100 additional uremic solutes have beenidentified, many of which are thought to betoxic. As kidney function deteriorates, thesesolutes can build up, contributing to the

276 Periodontal Disease and Overall Health: A Clinician's GuideTable 1. Classification of Chronic Kidney DiseaseGFRAction RequiredDisease Stage mL/min/1.73 m 2 (Additional to Previous Stage)Patient with risk factors for CKD ≥ 90 Reduce risk factors1. Kidney damage with normal or increased GFR ≥ 90 Diagnose and treatcomorbidities andCVD risk reduction2. Kidney damage with slight GFR decrease 60–89 Estimate progression3. Kidney damage with moderate GFR decrease 30–59 Treat complications4. Kidney damage with severe GFR decrease ≥ 15–29 Consider kidney replacement5. Kidney failure < 15 or Replace kidneydialysisCKD is defined as either kidney damage (pathological abnormalities in blood, urine, or imaging) or a GFR less than60 for three months or longer. (Table modified from KDOQI 2002. 11 )uremic syndrome. The uremic syndrome hasbeen associated with an increase in fatigue,anorexia, and mental status changes, and hasbeen shown to cause leukocyte dysfunction,insulin resistance, and decreased plateletfunction.Decreased kidney perfusion causes therelease of renin by granular cells in the juxta -glomerular apparatus. This release contrib -utes to the renin-angiotensin-system, leadingto multiple local and systemic effects, includingvasoconstriction, sodium reabsorption,and fluid retention. There are multipleantihypertensive agents targeting this system,including angiotensin converting enzyme(ACE) inhibitors, angiotensin II receptorblockers (ARBs), and a new class ofdirect renin inhibitors (DRIs).Patients with CKD and ESRD are at riskfor developing bone disease secondary tothe electrolyte and endocrine derangementsthat occur with decreased kidney function.As kidney disease progresses, phosphateexcretion is impaired. Additionally, there isdecreased production of active vitamin D.Vitamin D is either synthesized in the skin afterexposure to ultraviolet light or absorbedfrom dietary sources. However, vitamin Dfrom ultra violet light or dietary sources is notactive. It must undergo two hydroxylation reactionsto be activated in the body. The firsthydroxylation reaction occurs in the liverand the final hydroxylation reaction occursin the kidney. Decreased active vitamin Dlevels in combination with decreased phosphorousexcretion leads to hypocalcemia,hyperphosphatemia, and secondary hyperparathyroidism.Long-standing derangementsin calcium and phosphorus homeo stasiseventually lead to renal osteodystrophy,which is associated with impaired bone mineralization,increased risk of fractures, andcalcification.Overview of CKDCKD is a broad term used to encompasspatients with evidence of permanentkidney damage and/or progressive decreasein kidney function as defined by glomerularfiltration rate (GFR). 11 It is estimated that 31million Americans suffer from CKD andmillions of others are at risk (from NationalHealth and Nutrition Examination Surveydata 1999-2006). The most common causesof CKD include diabetes, hypertension, andglomerulonephritis.The National Kidney Foundation haspublished staging guidelines for adult patientswith CKD. These guidelines are basedon estimated GFR, which is calculated usingthe widely accepted Modification of Dietin Renal Disease (MDRD) equation. The

CHAPTER 17 Dental and Medical Comanagement of Osteoporosis,CHAPTER 17 Kidney Disease, and Cancer 277equation uses serum creatinine level combinedwith the variables of age, sex, and racein the estimation of GFR. (MDRD equation:GFR [mL/min/1.73 m 2 ] = 186 [S cr] -1.154 [age] -0.203 [0.742 if female] [1.212 ifAfrican-American] [conventional units]).This equation provides a much better estimateof kidney function than creatininealone. 11 Creatinine is a byproduct of muscleand thus creatinine levels vary with musclemass. Two individuals with the same creatininecan have striking differences in GFRbecause of differences in muscle mass. Forexample, an 80-year-old Caucasian femalewith a creatinine of 1 mg/dL has a decreasedestimated GFR of 57 mL/min/1.73 m 2 , whilea 30-year-old African-American male with acreatinine of 1 mg/dL has a normal estimatedGFR of 123 mL/min/1.73 m 2 .Renal Replacement TherapyCKD patients with a GFR of less than15 mL/min/1.73m 2 are considered to be inkidney failure. Most patients at this level ofkidney function present with symptoms ofuremia, and renal replacement therapy mustbe initiated to sustain life. Occasionally, a patientwill have symptoms of uremia requiringrenal replacement therapy prior to reachinga calculated GFR of < 15. Any patient witha GFR of < 15 or who is on dialysis is consideredStage V CKD.Renal replacement therapies include hemodialysis,peritoneal dialysis, and kidneytransplantation. Dialysis provides a mechanismfor filtration of waste products, removalof excess fluid, and titration of electrolytes.Dialysis does not replace the endocrine functionsof the kidney. Therefore, many dialysispatients rely on exogenous sources of erythro -poietin and vitamin D as part of their treatmentregimen. Patients undergoing transplantationrecover complete kidney function.However, they must remain on lifelongimuno suppressive therapy to prevent allograftrejection.Medications Used for CKDAntihypertensive AgentsMany patients with CKD have hypertensionand require multiple medications toreach adequate blood pressure control. Furthermore,the target blood pressure for patientswith CKD, at 130/80, is lower than itis for the general population (according tothe Joint National Committee on Hypertension7). Major classes of antihypertensiveagents include diuretics, beta blockers, ACEinhibitors, ARBs, and calcium channelblockers. Direct vasodilators, alpha blockers,and centrally acting agents represent less frequentlyused agents. Finally, the newest categoryof antihypertensives, DRIs, just becameavailable. Of these agents, calciumchannel blockers have been implicated as asource of gingival hyperplasia.Calcium channel blockers consist of dihydropyridinesand non-dihydropyridines.The dihydropyridines include amlodipine,felodipine, isradipine, nicardipine, nifedipine,and nisoldipine. The non-dihydropyridinesinclude diltiazem and verapamil. Bothclasses of calcium channel blockers reduceblood pressure by relaxing arteriole smoothmuscle and reducing systemic vascular resistance.The non-dihydropyridines also havea significant effect on heart rate through adirect negative chronotropic effect. Calciumchannel blockers have been documented tocause gingival hyperplasia in multiple reports(Figure 4). It is a potential adverse effect withall classes of calcium channel blockers, but isthought to occur more often with the dihydropyridineagents. 10 Gingival hyperplasiausually occurs within months after the initiationof therapy and resolves within monthsof discontinuing therapy. 12 Clinicians mayconsider discontinuing these medications inpatients with calcium channel blocker-inducedgingival hyperplasia. However, careshould be made to find an alternative antihypertensiveto help maintain adequate bloodpressure control.

278 Periodontal Disease and Overall Health: A Clinician's GuideFigure 4. Gross Gingival Hyperplasia inFigure 4. the Upper Anterior Region of aFigure 4. Patient with Hypertension onFigure 4. Treatment with a CalciumFigure 4. Antagonist (Dihydropyridine)Immunosuppressive TherapyPatients who have undergone kidneytransplantation require immunosuppressivetherapy to prevent rejection. There are bothcell-mediated and humeral components totransplant rejection. Transplant medicationstarget both aspects of transplant rejection.Most regimens include calcineurin inhibitorsto decrease the T-cell mediated response.The calcineurin inhibitors include cyclosporineand tacrolimus. Cyclosporine hasbeen documented to cause gingival hyperplasiain renal transplant patients in multiplestudies. 13 Additionally, this effect is thoughtto be augmented when cyclosporine is usedin combination with a calcium channelblocker. 14 Tacrolimus has shown muchlower rates of gingival hyperplasia and maybe a safe alternative for a patient experiencingsignificant cyclosporine-induced hyperplasia.14,15 Any change in transplant medicationsshould be made by a transplantspecialist to ensure efficacy and safety. Anotherapproach to treating gingival hyperplasiamight be the combination of a standardoral hygiene program and azithromycintherapy, which has been shown in at leastone study to reduce both symptoms and objectivemeasures of cyclosporine-inducedgingival hyperplasia. 16Inflammatory StateThe relationship of kidney disease toperiodontal disease is a complex one that requiresfurther study. Periodontal disease contributesto a chronic inflammatory state thathas been linked to multiple systemic illnesses.Two recent cross-sectional studiesidentified periodontal disease as an independentrisk factor for chronic kidney disease.However, the temporal relationship betweenthe two is unknown and noconclusions can be made on causality. 17-19Patients with CKD, especially those ondialysis, have exceedingly high mortalityrates. Recent data from the US Renal DataSystem (USRDS) show a mortality rate of84 deaths per 1,000 patient-years amongdialysis patients ages 20 to 44, and 174deaths per 1,000 patient-years among those45 to 64 years of age. These rates representan eight-fold increase from the general population.The leading cause of morbidity andmortality of CKD patients is cardiovasculardisease.The increased prevalence of cardiovasculardisease among CKD patients is thoughtto be multifactorial. Many CKD patientshave well-known risk factors associated withcardiovascular disease, such as hypertensionand dyslipidemia. However, chronic inflammationis a potential risk factor for cardiovasculardisease in CKD patients. Reductionin kidney function is associated withincreased serum levels of inflammatory cytokinesand C-reactive protein (CRP) anddecreased levels of albumin. This inflammatorystate appears to accelerate the progressionof vascular disease.Furthermore, periodontal disease mayadd to this inflammatory burden in patientswith CKD. Periodontal disease is commonin CKD patients, often more severe than inthe general population, and is frequentlyoverlooked. 20 Death from diabetic nephropathy,and ESRD are significantly greater indiabetic patients with periodontal disease

CHAPTER 17 Dental and Medical Comanagement of Osteoporosis,CHAPTER 17 Kidney Disease, and Cancer 279compared to those with diabetes and little orno periodontal disease. 21,22 Multiple studieshave shown the association of inflammatorymarkers to periodontal disease in dialysispatients. 23,24 Treatment of periodontal diseasehas been shown to reduce inflammatorymarkers in non-CKD patients. 25 Furthermore,in a study of CKD patients, treatmentof periodontal disease was shown to significantlydecrease CRP levels. 24 Measures thatdecrease periodontal disease in the CKDpopulation may ultimately reduce the inflammatoryburden of the CKD patient, thusdecreasing the mortality from cardiovasculardisease, but no such study has been performed.Another potential benefit from decreasinginflammatory markers in CKD patients isdecreased use of erythropoietin-stimulatingagents. Elevated CRP levels in patients ondialysis are associated with higher doses oferythropoietin. 23 Furthermore, the most recentinformation from the USRDS showsthat Medicare spent $1.9 billion on erythropoietin-stimulatingagents in one year alone.Decreasing CRP might result in lower erythropoietindoses and thus have a large andpositive financial impact.Treatment of Periodontal Diseasein the CKD PatientThe management of periodontal diseasefrequently requires significant instrumentation,pharmacotherapy, and sometimes surgery.Some clinicians recommend antibioticprophylaxis prior to dental procedures in patientswith arterial venous grafts because ofthe risk of infective endocarditis. 26 Multipleantibiotic and analgesic regimens exist. Forall antibiotics, it is important to adjust dosebased on GFR and avoid nephrotoxic agentsin patients who are not yet on dialysis. Nonsteroidalanti-inflammatory drugs (NSAIDs)can decrease GFR and are best avoided inpatients with CKD. Patients with CKD maybe at increased bleeding risk secondary toplatelet dysfunction, as well as anticoagulantsreceived on hemodialysis. One mighttry to implement a procedure on the day followingdialysis to decrease the risk. 10 Mostrenal transplant protocols include a dentalworkup prior to transplantation to treat anypotential problems once immunosuppressivetherapy is initiated. Extra caution is necessaryin renal transplant patients as they aremore susceptible to infection.CANCER ANDPERIODONTAL DISEASEAlmost 11 million people in the US areliving with cancer or have a history of cancer,with approximately 1.4 million new cases occurringyearly. 27 “Cancer” is a broad termused to describe a group of illnesses definedby uncontrolled growth of abnormal cells thatcan occur anywhere in the body. Many environmentaland intrinsic factors have been implicatedin the development of various formsof cancer. Environmental factors include tobacco,chemicals, radiation, and infection.Intrinsic factors include gene mutations, hormones,and immune conditions. Many cancersare likely caused from a combination ofenvironmental and intrinsic factors. 27Patients with cancer represent a uniquesegment of the dental population. Many patientswith cancer have pre-existing periodontaldisease at the time of cancer diagnosis.Additionally, several cancer treatmentsare toxic to oral tissues and can worsen underlyingoral disease or result in the developmentof new periodontal disease. Cancertreatments include chemotherapy, radiationtherapy, surgery, hormone therapy, biologictherapy, and targeted therapy. Furthermore,some cancers may involve the oral cavityand have a local effect on oral tissues.In recent years, periodontal disease hasbeen shown to have an association with manychronic diseases, including cardio vasculardisease and diabetes. Much of this associationis thought to be secondary to the chronic inflammatorystate. 28 Recent studies have shown

280 Periodontal Disease and Overall Health: A Clinician's Guidea small but significant increase in cancer riskin patients with periodontal disease. 29,30ChemotherapyChemotherapeutic regimens were developedto target rapidly dividing cells suchas tumor cells. With that concept in mind, itis logical to draw an association betweenthese therapies and side effects impactingthe gastrointestinal tract. Oral toxicity associatedwith chemotherapy in cancer patientsis a common side effect of these medicalregimens, which can affect the entire alimentarytract. Symptoms are numerous, includinglesions of the oropharynx, dysphagia,gastritis, and diarrhea.Mucositis is a term used to describe inflammationof the mucous membranes liningthe oral cavity and digestive tract. Oral mucositisis commonly reported and is estimatedto be found in 35% to 40% of patientsreceiving cytotoxic chemotherapy, and a higherprevalence in those undergoing hematopoieticstem cell transplantation (HCT). 31Multiple factors contribute to the developmentof mucositis. Tissue damage/cell death,stimulation of a pro-inflammatory state, andinterference with normal tissue healing aredirect and indirect effects of the medications.This final chapter section focuses on complicationsof chemotherapeutic regimens andHCT involving the oropharynx, pretreatmentconsiderations, and management of theseissues.Chemotherapeutic EffectsThere are numerous chemotherapy regimensavailable depending on the type ofcancer being treated. Some of the more commonagents associated with oral toxicity includealkylating agents, anthracyclines, anti -metabolites, antitumor antibiotics, taxanes,and topoisomerase inhibitors. There aremany more anticancer drugs associated withoral toxicity and a more comprehensive listcan be seen in Table 2. While the individualmechanism of action of these medications isnot essential to this discussion, it is importantto understand how they exert their effectson tissues. Reactive oxygen species causedamage to the DNA of tumor cells as well ashealthy tissue. Damaged cells undergo apoptosis,setting into motion the body’s normalresponse to cell death, which includes increasedactivity of the immune system. Activationof the immune system increases theconcentration of pro-inflammatory moleculesin the internal milieu, such as cytokinesand biologically active proteins. Normalhealing is compromised by the persistence ofthe offending agent.Oral MucositisUlcerative oral mucositis is one of themore common side effects associated withchemotherapy. As previously mentioned,prevalence among cancer patients treatedwith chemotherapeutic regimens can be ashigh as 40% or even higher in patients under -Table 2. Chemotherapeutic Agents Associated with Oral Toxicity and MucositisDrug CategoryChemotherapeutic Drug Names (Generic)Alkylating agentsbisulfan, carboplatin, cisplatin, cyclophosphamide, ifofamide,mechloethamine, melphalan, procarbazine, thiotepaAnthracyclinesdaunorubicin, doxorubicin, iadarubicin, epirubicin, mitoxantroneAntimetabolitescapecitabine, cytarabine, fluorouracil, fludarabine, gemcitabine,hydroxyurea, methotexate, 6-mercaptopurine, pemetrexed, 6-thioguanineAntitumor antibioticsdactinomycin, bleomycin, mitomycinTaxanesdocteaxel, paclitaxelTopoisomerase inhibitors etoposide, topotecan, irinotecan, teniposideAdapted from UpToDate, 2010.

CHAPTER 17 Dental and Medical Comanagement of Osteoporosis,CHAPTER 17 Kidney Disease, and Cancer 281going HCT. Intensive chemotherapy cancause ulcerative mucositis that emerges approximatelytwo weeks after initiation ofhigh-dose chemotherapy. 32 Risk factors fordevelopment of mucositis include youngerage, quality of dental hygiene, and level ofimmunosuppression prior to the initiation oftherapy. The ulcerations associated with oralmucositis can be extremely painful and mayinterfere with the patient’s capacity for requirednutritional intake. Subsequent infectionis another noted problem associated withthese lesions. Considering the level of immunosuppressionlinked to chemotherapy,these are clinical findings that need to beidentified and addressed in a timely fashionby medical and dental practitioners. If symptomsare severe, modification of thechemotherapeutic agents as well as dosingmay be necessary. Mucositis is considered tobe self-limited and usually resolves within14 days of cessation of chemotherapy. Thismay coincide with the recovery of granulocytes,but has not been shown to have a linearrelationship. Other less common side effectsinclude xerostomia, hemorrhage, andneuropathy.Preventing Oral MucositisThere is limited objective data to supportthe concept of dental therapy prior to theinitiation of treatment for cancer. Whilemany feel that aggressive preventive dentalcare limits the extent of oral complicationsassociated with such medical therapy, onestudy proposed that such measures had noimpact on overall outcome. 33 Practice guidelinesconcerning oral prophylaxis for mucositiswere published in 2007 by the MucositisStudy Section of the MultinationalAssociation of Supportive Care in Cancerand the International Society for Oral Oncology(MSSMA/SCCISO). 34 For patientsundergoing standard chemotherapy, evaluationby a dental practitioner is encouragedprior to the initiation of therapy. Intervalassessment is recommended to evaluate oralcavity health, including the use of validatedtools such as the National Cancer InstituteCommon Toxicity Criteria or the Universityof Nebraska Oral Assessment Score to ascertainthe severity and clinical course ofmucositis.In those patients undergoing high-dosechemotherapy plus HCT, preventive measureshave recently been developed and arecurrently recommended for routine use. Paliferminis a keratinocyte growth factor-1stimulator. It accelerates growth of epidermalcells including those of the gastrointestinaltract. In a double-blinded randomized controltrial, it was shown to reduce the incidence ofsevere mucositis compared with the placebogroup. 35 The use of granulocyte-macrophagecolony-stimulating factor mouthwashes arealso recommended for the prevention of mucositisin this patient population. Low-levellaser therapy has been recommended in clinicalguidelines as part of pretreatment forHCT patients. However, this therapy is expensiveand not widely available, and thereis limited objective evidence to support itsefficacy. The use of cryotherapy is also recommendedfor the prevention of oral muco -sitis. It is important to remember that manyof these guidelines are based on expert opinion;further clinical research is necessary tovalidate the use of these protocols.Treating Oral MucositisThe treatment of established oral muco -sitis is supportive. Soft diets are a good choiceto reduce the incidence of trauma to alreadyfriable tissue. Practitioners need to encouragesound oral hygiene practice as this will reducethe incidence of secondary infection andpromote timely healing. Soft toothbrushes,non-irritating oral rinses, and removal of denturesshould all be encouraged as a part of routinecare. The use of mucosal coating agentshas been employed, although the data to supportthe efficacy of such agents are weak.

282 Periodontal Disease and Overall Health: A Clinician's GuideOral solutions including lidocaine, diphenhydramine,and morphine sulfate have all beenemployed as analgesic control for oral mucositis.The MSSMA/SCCISO panel recommendedsystemic morphine as the treatmentof choice for HCT patients with oral painassociated with severe oral mucositis. 34Cautious evaluation of the neutropenicpatient is critical. These patients may presentwith reduced signs and symptoms secondaryto myelosuppression. Antimicrobial therapyearly in the course of infection is required toavert potentially catastrophic complications.Studies have shown that oral and periodontalassessment and management reduces therisk of infection and fever associated withoral conditions. 36 Studies have also shownthat pretreatment oral care and oral care duringtherapy results in reduced oral complicationswith no increase in risk of fever orbacteremia. 36In summary, the complication of oralmucositis has a very high prevalence amongcancer patients treated with chemotherapy.Clinical guidelines were published in 2007outlining recommendations for the pretreatmentof cancer patients at risk for developingoral mucositis. While preventive measuressuch as palifermin and cryotherapy arerecommended for high-dose chemotherapypatients, the basis of care is sound oral hygieneand regular assessment by a dentalpractitioner. Although oral mucositis is consideredto be a self-limiting phenomenon,supportive care is necessary to amelioratethe invasive symptoms associated with thiscomplication. Special attention needs to begiven to the neutropenic patient as infectionin this patient population is potentially lifethreatening.Leukemia and the Oral TissuesLeukemia, a disease of the bone marrowand blood, is characterized by the malignantproliferation of white blood cells. Leukemiasare further categorized based on the cell typethat is involved; these are divided into myelo -genous and lymphocytic. Futhermore, leuke -mias are categorized as acute or chronic.Chronic leukemias occur more commonlyin older individuals and are characterized bythe excessive proliferation of relatively mature,abnormal white blood cells. Typically,these leukemias progress over a period ofmonths to years. Acute leukemias are characterizedby a rapid proliferation of im -mature white blood cells. Acute leukemiasare the most common form of leukemia inchildren, but can also affect adults. The fourmajor classifications of leukemia are acutelympho cytic leukemia, acute myelogenousleukemia, chronic lymphocytic leukemia,and chronic myelogenous leukemia. Withinthese main categories exist several subtypes.Additionally, there are some less-commonforms of leukemia that do not fit well intoany of these categories.In all forms of leukemia, bone marrowfunction is impaired. Anemia, thrombocytopenia,and impaired immunity often result.These changes can result in gingival hemorrhage,oral ulcerations, and increased oralinfections. 37,38 The use of chemotherapyand stem cell transplantation can contributefurther to this by causing increased bonemarrow suppression as well as toxic effectson oral tissues.When evaluating a leukemic patientwith gingival lesions, it is often difficult todistinguish between changes due to the diseaseprocess and those brought on by treatment.In order to better characterize gingivallesions in patients with leukemia, a classi -fication system has been proposed. Thisclassification system consists of four majorcategories: direct infiltration, direct drugtoxicity, graft-versus-host disease, and bonemarrow/lymphoid tissue suppression. 39It is important for dental practitioners torecognize that a patient may present withoral lesions prior to the diagnosis of leuke -mia. Case reports have described gingival

CHAPTER 17 Dental and Medical Comanagement of Osteoporosis,CHAPTER 17 Kidney Disease, and Cancer 283hyperplasia, rapidly progressive periodontaldisease, prolonged post-extraction hemorrhage,and gingival pain as presentingsymptoms that led to various leukemiadiagnoses. 37,40Radiation Therapy inHead and Neck CancerHead and neck cancers include cancerof the oral cavity, the pharynx, the larynx,salivary glands, nasal cavity, paranasal sinuses,and neck lymph nodes. The majorityof head and neck cancers are squamous cellcarcinomas. Patients undergoing head andneck radiation treatments are at risk for avariety of oral complications. These complicationsinclude mucositis, dysgeusia (alteredsense of taste), xerostomia (dry mouth),dental caries, periodontal disease, and osteo -radionecrosis. Collaboration among physiciansand dental professionals is necessary toprovide optimal care.Preradiation oral assessment and intervention,followed by the implementation ofan oral care program prior to and during radiation,is essential to improve outcomes inpatients undergoing radiation. A recent surveyof healthcare professionals reported a75% referral rate for oral and dental assessmentprior to head and neck radiation. Thesame survey also reported that integrateddental and medical services were available atonly 25% of institutions. 41Mucositis is a common side effect ofradiation therapy and has been reported in upto 80% of patients receiving radiotherapyfor head and neck cancer. 42 Radiation disruptsDNA replication in the basal layer ofthe oral epithelium. This leads to thinning ofthe epithelium and eventual ulceration oforal tissues. The ulcerative phase is worsenedby local bacterial colonization. 42As in patients with chemotherapy-inducedmucositis, the cornerstone of therapyin patients with radiation-induced mucositisincludes adequate pain management andmaintenance of oral hygiene. Recent guidelinesspecific to radiation-induced mucositissupport the use of midline radiation blocksand 3-dimensional radiation therapy to minimizemucosal damage. The guidelines alsorecommend the use of benzydamine, a locallyacting NSAID, for mucositis prevention inpatients exposed to moderate doses of radiation.Because of a lack of clinical benefit,the guidelines recommend against routineuse of chlorhexidine rinses and antimicrobiallozenges to prevent radiation-induced oralmucositis. They also recommend against theuse of sucralfate in the treatment of radiationinducedmucositis. 34Dysgeusia and xerostomia are commonside effects of radiation. Radiation therapycan damage taste buds, and in some caseslead to permanent taste loss. Radiation leadsto atrophy, vascular damage, and connectivetissue fibrosis of the salivary glands. Theresult is both dose- and location-dependent.Higher radiation doses and involvement oflarge areas of salivary tissue will result inmore severe cases of xerostomia. Patientswith significant xerostomia are at muchhigher risk for developing dental caries. Forthese patients, daily fluoride treatment andmeticulous oral hygiene is recommended forthe prevention of dental decay.Radiation can lead to alterations in vascularityof soft tissue and bone, reduced connectivetissue cellularity, and increased tissuefibrosis. The vascular changes result in decreasedblood flow to tissues, with concomitanttissue hypoxia and reduction in tissuecellularity. This can have a deleteriouseffect on bone and soft tissue in the oral cavity.High-dose radiation has been shown tocontribute to tooth loss and greater perio -dontal attachment loss. Furthermore, perio -dontal attachment loss has the potential tolead to osteoradionecrosis. 43Osteoradionecrosis is a less common, butpotentially devastating side effect of radiationthat primarily occurs in the mandible, and

284 Periodontal Disease and Overall Health: A Clinician's Guideis a condition defined by exposed bone inareas of radiation injury. A recent retrospectivestudy of 207 patients who receivedradiation therapy showed osteoradionecrosisin 5.5% of patients. 44 This com -plication of radiation therapy occurs as aresult of decreased wound healing. It canoccur spon taneously, but more frequentlyoccurs after tissue trauma resulting inexposed bone, especially dental extraction.Preradiation assessment for potential problemsand appropriate preradiation extractionscan help limit postradiation dentalextractions and the potential developmentof osteo radio necrosis.SurgerySurgical resection is an important treatmentmodality for head and neck cancers.Unfortunately, these surgeries are frequentlydisfiguring and debilitating. Furthermore,infection of the oral cavity can lead to significantsetbacks in recovery, as well as delayadjunctive chemotherapy or radiation.Thorough preoperative oral and dental evaluationcan help improve outcomes. Patientswho undergo significant resections often requireremovable prostheses to maintain functionand may also undergo skin grafting aspart of the surgical procedure. There are intra-oralprostheses that can aid in speech andnutrition, while extra-oral prostheses canhelp to reduce disfiguration. Regardless ofthe type of prosthesis, a preoperative meetingwith the patient and family can help themknow what to anticipate postoperatively.Close postoperative monitoring of the surgicalsite is essential. When applicable, theskin graft site should be monitored for viability.During the initial postoperative evaluation,the patient can be instructed in anoral care regimen, as well as oral openingexercises to aid in a recovery of function.There are several commercially availablemechanical devices that can aid in oral openingexercises. 45,46Periodontal Disease and Cancer RiskThis chapter section has focused on theeffect of cancer treatments on oral tissues. Amultidisciplinary approach, with involvementof medical and dental professionals, isnecessary to optimize oral care in cancer patients.However, it must be noted that poororal health may be a risk factor for the developmentof cancer. Multiple studies havedemonstrated the inflammatory effects ofperiodontal disease, and this inflammatorystate might have an effect on the developmentof cancer. There appears to be a relationshipbetween tooth loss and head andneck cancer that is independent of alcoholand tobacco use. Furthermore, tooth loss hasbeen shown to be a risk factor for the develop -ment of esophageal, gastric, and pancreaticcancers. Additionally, periodontal diseasehas been associated with a small, but significantincrease in overall cancer risk. 29,30Recommendations for Cancer andPeriodontal Disease ManagementPatients with cancer represent a uniquesegment of the dental population. Many cancertreatments are toxic to oral tissues. Onthe other hand, chronic oral infectious andinflammatory conditions such as periodontaldisease and endodontic lesions may contributeto cancer risk, and if they persist orexacerbate during cancer therapy, they couldbe a source of life-threatening infection. Pretreatmentdental evaluation of the cancerpatient is highly recommended and can helpidentify potential problems and facilitate themanagement of anticipated side effects oftherapy.Dentists and physicians need to worktogether to plan care for their patients; inparticular, there should be:A pretreatment oral evaluation for anyexisting periodontal, carious, or endodonticproblems that may be a future source ofchronic infection or may be exacerbatedby cancer treatment or if cancer therapy

CHAPTER 17 Dental and Medical Comanagement of Osteoporosis,CHAPTER 17 Kidney Disease, and Cancer 285involves treatments that reduce resistance toinfection.Treatments that may induce xerostomia,such as radiation therapy, should be performedonly with the understanding that thereduced salivary flow may result in rampantcaries and oral mucosal problems that needto be regularly checked for and treated.Supplemental ReadingsKhosla S, Burr D, Cauley J, Dempster DW, Ebeling PR,Felsenberg D, Gagel RF, Gilsanz V, Guise T, Koka S,McCauley LK, McGowan J, McKee MD, Mohla S,Pendrys DG, Raisz LG, Ruggiero SL, Shafer DM,Shum L, Silverman SL, Van Poznak CH, Watts N, WooSB, Shane E. Bisphosphonate-associated osteonecrosisof the jaw: report of a task force of the American Societyfor Bone and Mineral Research. J Bone Miner Res2007;22:1479 –1491.Craig RG. Interactions between chronic renal diseaseand periodontal disease. Oral Dis 2008;14:1–7.Kadiroglu AK, Kadiroglu ET, Sit D, Dag A, YilmazME. Periodontitis is an important and occult source ofinflammation in hemodialysis patients. Blood Purif2006;24:400–404.Williams RC, Barnett AH, Claffey N, Davis M, GadsbyR, Kellett M, Lip GY, Thackray S. The potential impactof periodontal disease on general health: a consensusview. Curr Med Res Opin 2008;24:1635–1643.Epstein JB, Stevenson-Moore P. Periodontal diseaseand periodontal management in patients with cancer.Oral Oncol 2001;37:613–619.Jham BC, Reis PM, Miranda EL, Lopes RC, CarvalhoAL, Scheper MA, Freire AR. Oral health status of 207head and neck cancer patients before, during and afterradiotherapy. Clin Oral Investig 2008;12:19–24.Toth BB, Chambers MS, Fleming TJ, Lemon JC,Martin JW. Minimizing oral complications of cancertreatment. Oncology (Williston Park) 1995;9:851–858;discussion 858, 863–866REFERENCES1. Mauck KF, Clarke BL. Diagnosis, screening, prevention,and treatment of osteoporosis. Mayo ClinProc 2006;81:662–672.2. Ettinger MP. Aging bone and osteoporosis: strategiesfor preventing fractures in the elderly. Arch InternMed 2003;163:2237–2246.3. Qaseem A, Snow V, Shekelle P, Hopkins R Jr,Forciea MA, Owens DK. Screening for osteo -porosis in men: a clinical practice guideline fromthe American College of Physicians. Ann InternMed 2008;148:680–684.4. Polednak AP. Rates of Paget’s disease of boneamong hospital discharges, by age and sex. J AmGeriatr Soc 1987;35:550–553.5. Chavassieux PM, Arlot ME, Reda C, Wei L, YatesAJ, Meunier PJ. Histomorphometric assessment ofthe long-term effects of alendronate on bone qualityand remodeling in patients with osteoporosis.J Clin Invest 1997;100:1475–1480.6. Fleisch H. Bisphosphonates: mechanisms of action.Endocr Rev 1998;19:80–100.7. Khosla S, Burr D, Cauley J, Dempster DW, EbelingPR, Felsenberg D, Gagel RF, Gilsanz V, Guise T,Koka S, McCauley LK, McGowan J, McKee MD,Mohla S, Pendrys DG, Raisz LG, Ruggiero SL,Shafer DM, Shum L, Silverman SL, Van PoznakCH, Watts N, Woo SB, Shane E. Bisphosphonateassociatedosteonecrosis of the jaw: report of a taskforce of the American Society for Bone and MineralResearch. J Bone Miner Res 2007;22:1479–1491.8. Sambrook P, Olver I, Goss A. Bisphosphonates andosteonecrosis of the jaw. Aust Fam Physician 2006;35:801–803.9. Woo SB, Hellstein JW, Kalmar JR. Narrative [corrected]review: bisphosphonates and osteonecrosisof the jaws. Ann Intern Med 2006;144:753–761.10. Proctor R, Kumar N, Stein A, Moles D, Porter S.Oral and dental aspects of chronic renal failure. JDent Res 2005;84:199–208.11. National Kidney Foundation. K/DOQI ClinicalPractice Guidelines for Chronic Kidney Disease:Evaluation, classification and stratification. GuidelinesK. Part 4. Definition and classification ofstages of chronic kidney disease Am J Kidney Dis2002;39:S46–S75.12. Missouris GG, Kalaitzidis RG, Cappuccio FP, Mac-Gregor GA. Gingival hyperplasia caused by calciumchannel blockers. J Hum Hypertens 2000;14:155–156.13. Craig RG. Interactions between chronic renal diseaseand periodontal disease. Oral Dis 2008;14:1–7.14. Spolidorio LC, Spolidorio DM, Massucato EM,Neppelenbroek KH, Campanha NH, Sanches MH.Oral health in renal transplant recipients administeredcyclosporin A or tacrolimus. Oral Dis 2006;12:309–314.15. Ellis JS, Seymour RA, Taylor JJ, Thomason JM.Prevalence of gingival overgrowth in transplantpatients immunosuppressed with tacrolimus. J Clin

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CHAPTER 17 Dental and Medical Comanagement of Osteoporosis,CHAPTER 17 Kidney Disease, and Cancer 28743. Epstein JB, Lunn R, Le N, Stevenson-Moore P. Periodontal attachment loss in patients after head andneck radiation therapy. Oral Surg Oral Med OralPathol Oral Radiol Endod 1998;86:673–677.44. Jham BC, Reis PM, Miranda EL, Lopes RC, CarvalhoAL, Scheper MA, Freire AR. Oral health status of 207head and neck cancer patients before, during and afterradiotherapy. Clin Oral Investig 2008;12:19–24.45. Toth BB, Chambers MS, Fleming TJ, Lemon JC,Martin JW. Minimizing oral complications of cancertreatment. Oncology (Williston Park) 1995;9:851–858; discussion 858, 863–856.46. Chambers MS, Toth BB, Martin JW, Fleming TJ,Lemon JC. Oral and dental management of the cancerpatient: prevention and treatment of complications.Support Care Cancer 1995;3:168–175.

288 Periodontal Disease and Overall Health: A Clinician's GuideCHAPTER 18The Role of the Professionalin Educating the Public Aboutthe Importance of Oral HealthCasey HeinINTRODUCTIONIt has been recognized for some timethat health outcomes are, in part, a functionof health literacy and education of the public. 1The level of health literacy, or level of knowledgenecessary to guide healthy living withina population, is one of the strongest socialdeterminants of health within a society. Limitedhealthcare literacy has been implicated inundermining the public’s ability to fully benefitfrom what healthcare systems have to offer.Lack of oral health knowledge presentsan obstacle to better oral healthcare in theUnited States; 2,3 almost half of all Americanslack adequate oral health skills, which mayaccount for billions of dollars in addedhealthcare costs each year. 2,3 It is importantto consider whether or not lack of adequatepractitioner-to-patient communication maybe implicated in the challenges we face regardingoral health literacy.Oral diseases are often a source of overlookedinfection and systemic inflammationthat has the potential to affect overall health.As such, oral diseases have been termed a“silent epidemic.” 4 Given the strength ofevidence that supports inter-relationshipsbetween oral and overall health, educatingconsumer-patients about the threat that oralinfections may pose to general health canno longer be considered optional. Both dentaland nondental healthcare practitioners,such as physicians, nurses, and allied healthcareproviders, share in the responsibility toeducate the public regarding the significanceof oral health in achieving and sustainingwhole-body health. Codes of professionalconduct convey a responsibility of healthcarepractitioners to educate patients. Health outcomes—beyondthe oral cavity—may bepositively influenced by effective patient education and health literacy campaigns targetingoral health.Information about the relationship betweenoral and systemic health started to bedisseminated to the public from a number ofsources beginning in the 1990s. Various publicrelations campaigns have increased theawareness of the connection between oraland systemic health among a broad audienceof consumer-patients. Information from thelay press, mainstream radio and television,university- and government-sponsored publichealth outreach to local communities, insuranceindustry campaigns, and commercialadvertising associated with oral care productshave provided highly visible and effectivemechanisms for educating the publicabout the significance of oral health. However,nothing can be as powerful as practitioner-to-patienteducation. The time dentistsand dental hygienists spend with in di vidualpatients presents a valuable opportunity tocommunicate credible findings of researchrelated to systemic inflammation associatedwith oral infections. In addition, as pointof-careproviders, dental practitioners maybe uniquely positioned to identify patientswho may be at risk for chronic diseases, suchas diabetes and atherosclerotic diseases,which share risk factors common to oraldiseases.

Chapter 18Chapter 18 The Role of the Professional in Educating the Public About the Importance of Oral Health 289As the depth and breadth of evidence tosupport a relationship between periodontaldiseases and several common systemic inflammatorydiseases continues to expand,the preponderance of evidence suggests thatdental providers have a responsibility to appropriatelyand effectively communicate thisinformation to patients.In the case of diabetes, evidence frompilot trials shows that treatment of perio -dontal disease may improve metabolic controlof diabetes. 5-7 However, large-scale, definitivetrials are still needed to establish theefficacy of periodontal intervention. Similarly,in the case of pregnancy outcomes,several pilot trials have shown a reduction ofadverse pregnancy outcomes associated withperiodontal treatment. 8,9 However, a largestudy failed to show a reduction in adversepregnancy outcomes associated with treatmentof periodontal disease. 10 Several studieshave assessed the effect of periodontaltherapy on cardiovascular outcomes andhave shown improvement in endothelialfunction. 11-13 However, large, randomized,controlled trials are needed to look at the effectsof perio dontal therapy on cardiovascularoutcomes. Even though there are not yetdefinitive data on the effects of periodontaltreatment on several conditions associatedwith perio dontal disease, association dataare strong. Hence, educating patients aboutoral-systemic relationships is appropriate toensure that their treatment decisions are wellinformed.The medical profession has respondedto emerging evidence of periodontal-systemicrelationships with a number of articlesthat call attention to the likelihood thatperiodontal disease is an often overlookedand unrecognized source of infection with thepotential to evoke a systemic inflammatoryresponse. 14-16 As these kinds of evidencebased,authoritative statements are circulatedwithin the medical professions, it is reasonableto assume that more and more phy siciansand allied healthcare providers willacknowledge the significance of oral healthin achieving and sustaining overall health. Asa result, they will begin to screen for oral diseases,educate patients about oral-systemicconnections, and pursue collaborative relationshipswith dental practitioners in the comanagementof inflammatory-driven diseasestates. Already, informally gathered informationfrom physicians in specialties such as endocrinology,cardiology, obstetrics, rheumatology, pulmonology, and nephrology, amongothers, substantiate that medical practitionersare beginning to incorporate findings of credibleresearch of oral-systemic relationshipsinto their practices. Simultaneously, medicalprotocols that include periodontal evaluation,treatment, and monitoring of clinical outcomesrelated to the care of patients who maybe at greater risk for cardiovascular disease(CVD) and diabetes may also begin to emerge.Educational ObjectivesAfter reviewing the information presentedin this chapter, readers should be able to:• Discuss how the limitations in oralhealth literacy present a barrier to effectiveprevention, diagnosis, andtreatment of oral diseases.• Describe various sources of informationand statistics about the relationshipbetween oral and systemichealth that suggest consumer-patientsare aware of the importance of oralhealth in achieving and maintainingoverall health.• Identify various hurdles dental practitionersface in effectively educatingpatients about oral-systemic healthand describe ways to address theseobstacles.• Describe the responsibility of dentalprofessionals in ensuring that onlyscientifically supported evidence oforal-systemic relationships is communicatedto patients.

290 Periodontal Disease and Overall Health: A Clinician's Guide• Elaborate upon the professional developmentprocess that will distinguishindividual dentists and dental hy -gienists as authoritative experts in evi -dence of oral-systemic relationships.• Identify ways in which dentists anddental hygienists can influence thepublic’s perception of the importanceof oral health outside the practicesetting.THE PROCESS OF CHANGEIN INFLUENCING THEPUBLIC’S PERCEPTION OF THEIMPORTANCE OF ORAL HEALTH“Because oral diseases in general aretreatable and usually not life threatening,they have been erroneously perceived ashaving little relationship to other aspects ofhealth, often being viewed as of minor importancein the social and economic context.”17 This opinion reflects the all-too-realdisconnect between oral and overall healthand therefore has far-reaching implications.Segregation of the oral cavity from the restof the body—and consequently the historicalschism between dentistry and medicine—has helped contribute to the disparities thatcurrently exist in oral health among Americans.4 The failure to recognize oral health asintegral and essential to general health hasalso adversely impacted healthcare policy. 18In 2009, greater appreciation of the significanceof inflammation in prevention andmanagement of chronic diseases and mountingevidence in support of oral-systemic interrelationshipsat genetic and molecular levelsare changing nondental healthcare providers’perceptions of the importance of oral health.Indeed, the shift from an infection model toan inflammation model relative to the threatthat perio dontal disease poses to overall health,has gar nered the attention of the medical community.Medical journals—including some ofthe most prestigious—are reporting evidenceof oral-systemic relationships with increasedfrequency. In addition, governmental reports, 4,19educational institutions, 20,21 and professionalassociations 22 have called for educational reformthat would increase nondental healthcareproviders’ knowledge of oral health,and collaborative models of care that wouldbring together dental and nondental healthcareproviders to focus on interprofessional,comprehensive chronic disease managementthat includes oral care.The insurance industry has investigatedthe potential cost savings associated withtreatment of periodontal disease, and foundthat medical costs associated with chronicdiseases such as CVD and diabetes may besignificantly reduced when patients aretreated for periodontal disease. 23,24 Althoughthese studies do not prove cause and effect,they are sufficient for insurance companiesto be more liberal in their coverage for periodontaltherapy and maintenance for theirclients with diabetes and CVD. In addition,various guidelines created by health departmentsof state agencies have begun to addressthe importance of oral health in theoverall health of their citizenry. 25,26Changes in public policy, increased insurancereimbursement, and improved medical/dentaleducation undoubtedly will facilitateinterprofessional collaboration betweenthe healthcare professions; however, thismagnitude of change is unlikely to happen inthe short term. In the interim, educating thepublic through commercially supported mediacampaigns, outreach from professionalorganizations and universities, and individualpractitioner-to-patient education are essentialin helping the public reprioritize theimportance of oral health and its implicationto overall health.The answers to the following fourquestions provide a reference point to guidepractitioner-to-patient communication andarticulate messages that are essential tosuccessful patient education in oral-systemichealth:

Chapter 18Chapter 18 The Role of the Professional in Educating the Public About the Importance of Oral Health 2911. How much do consumer-patientsknow about the threat inflammationposes to whole body health and oralsystemicrelationships?2. How important do consumer-patientsbelieve oral health is to achievingand sustaining overall health?3. How well are dental practitioners doingregarding educating patientsabout oral-systemic relationships andwhat are the hurdles to effectivelycommunicating this information toconsumer-patients?4. What research should be credibly communicatedto patients about the relationshipbetween periodontal diseaseand inflammatory-driven diseasestates, such as coronary heart disease,stroke, diabetes, and adversepregnancy outcomes?5. In addition to individual practitionerto-patientcommunication, what typesof activities could dental practitionerspursue to change the perception ofnondental healthcare providers aboutthe importance of oral health, therebyincreasing the public’s awareness oforal-systemic relationships?CONSUMER-PATIENTS’KNOWLEDGE ABOUTORAL-SYSTEMIC LINKS, THESIGNIFICANCE OF ORAL HEALTH,AND THE THREAT INFLAMMATIONPOSES TO GENERAL HEALTHHelp from Mainstream MediaOver the last decade there have beennumerous sources of information from mainstreammedia about the relationship betweenoral and systemic health, including lay publications,27,28 television, 29 and radio. 30 In2004, Time Magazine 27 committed an entireissue, “The Secret Killer,” to help readers explorethe link between inflammation and variouslife-threatening conditions such as heartdisease. The article introduced readers tosome fairly sophisticated scientific conceptsthat describe how the body’s efforts to healthe damage produced by infection and inflammationoften end up causing permanentdamage to certain organs and increasing therisk for various systemic diseases. The articlespecifically discussed the potential of periodontaldisease to elicit such a cascade ofevents: “It appears that some people are moresensitive to plaques and tangles than others.Perhaps they have a genetic predisposition.Or perhaps a long-running, low-grade bacterialinfection, like gum disease, keeps theinternal fires burning and tips the balancetoward chronic infection.” 27 If readers cancomprehend such sophisticated information,it is reasonable to assume the public is becom -ing increasingly aware of the relationship be -tween periodontal disease and inflammatorydrivendisease states.CNN News jump-started the year 2009with a segment on “How to Live Longer,”which aired on January 2 and was hosted byDr. Sanjay Gupta, CNN’s Chief Medical Correspondent.29 Gupta discussed several simplemodifications to lifestyle that he proposedwould net increased longevity. He cited usingdental floss as the number one recommendation,explaining that oral care could reduce inflammation,a known contributor to increasedrisk for heart disease. These are only a few ofthe many examples of information on oralsystemichealth that have been generatedthrough mainstream media sources.A Snapshot of What the Public KnowsPiecing together data compiled by variousprofessional and nonprofit organizationsand the insurance industry provide a snapshotof how well the consumer-patient publicunderstands the importance of oral health inachieving and maintaining overall health.Findings of a survey conducted in the year2000 by the American Dental Associationindicated that the vast majority of consumer-

292 Periodontal Disease and Overall Health: A Clinician's Guidepatients are aware that there is a link betweenperiodontal disease and systemic consequences,and more than 99% recognize thatprevention of periodontal disease is an importantstep in maintaining oral health. 31Other data indicate that 85% of Americansbelieve there is a strong connectionbetween oral health and general health. 32 Thelarge majority (77%) of Americans believethat personal maintenance of their oral healthis very important to their own overallhealth, 33 and 80% of Americans agree thattaking care of one’s mouth, teeth, and gumsis “absolutely needed.” 2 When askedwhether “you take dental health into accountwhen rating your overall health,” 78% of respondentsof a randomly selected nationallyrepresentative survey of US adults indicatedthat they did. 34 A correlational analysis ofthe same data showed that the public’s ratingof oral and overall health were strongly related(r = .46, p < .001). These data suggestthat oral health and general health status areclearly connected in the consciousness ofAmericans. 34Patients’ Concerns AboutPeriodontal DiseaseOf 1,000 subjects from a randomlyselected, nationally representative survey ofUS adults, 85% reported that it was “very important”for dentists to examine their mouthsfor periodontal disease. 34 Other data confirmthat patients want to be evaluated for periodontaldisease because they are concernedabout the systemic implication of periodontaldisease. When briefly educated about the riskof systemic consequences related to periodontaldisease, and asked what kind of treatmentthey would prefer when they next visitthe dentist, two out of three consumer-patientsfrom a nationally representative sampleopted for periodontal examinations instead ofroutine prophylaxis. 35 The survey questionand results of the consumer-patient responsesare included in Figure 1.The Strength of PatientEducation CampaignsVarious professional organizations suchas the American Academy of Periodontology(http://perio.org/consumer/index.html), theoral care industry (http://www.colgate.com/app/ColgateTotal/US/EN/MBHC.cvsp), andnonprofit organizations such as the AmericanDiabetes Association (http://www.diabetes.org)among others, have mounted impressive webbasedpatient education campaigns targetingoral-systemic health.The contribution of medical providersin educating patients about the potential ofperiodontal disease to elicit systemic inflammationand increased risk for chronicdisease states cannot be overlooked. In aFebruary 2008 issue of the Journal of theAmerican Medical Association, 36 a patienteducation page (Figure 2) was dedicated toa discussion of periodontal disease and itspotential association to heart disease, stroke,and premature birth. The article briefly de -fined the causes, signs and symptoms, preven -tion, and treatment of periodontal disease,and offered other resources for additionalinformation.Summary Points1. Consumer-patients are very aware ofthe connection between oral healthand general health.2. A number of publications from thelay press and mainstream radio andtelevision have done an excellent jobof educating consumer-patients onthe threat that inflammation poses towhole body health and the potentialof periodontal disease to incite aninflammatory response.3. Consumer-patients seem to be awarethat prevention of periodontal diseaseis important in maintaining overallhealth, and subsequently want to beevaluated for periodontal disease becausethey are concerned about the

Chapter 18Chapter 18 The Role of the Professional in Educating the Public About the Importance of Oral Health 293Figure 1. Question on Consumer-Patient Survey Conducted in 2005.The survey question first provided a very brief overview of the risk “gum disease”may pose in increasing the risk for serious systemic diseases. Then consumer-patientswere asked to respond to how important it is to be examined for periodontal disease attheir next check-up visit. Results follow.It is estimated that 50%–80% of adults have some level of gum disease. More important thoughis that over the last 10 years there has been increasing evidence that periodontal disease may beassociated with serious systemic consequences. This includes the potential for increased risk forheart disease and stroke, and for pregnant women with periodontal disease an increased risk ofdelivering preterm, low birth weight infants. Individuals with impaired immune systems andperiodontal disease may have an increased risk for certain respiratory diseases. In addition,diabetics have an increased risk for developing periodontal disease and periodontal disease indiabetics often makes metabolic control of blood sugar levels very difficult. For this reason, it isvery important that diabetics have thorough periodontal evaluations.Question: Given the evidence that periodontal disease may be linked to these kinds of seriouswhole body diseases/conditions, at your next visit to the dentist’s office, would you rather beexamined for periodontal disease or have your teeth cleaned?❑ Examined for periodontal disease ❑ Have my teeth cleanedResults: There were 1,415 responses to this question. 945 (66.78%) of consumer-patients whoresponded answered that given the evidence that periodontal disease may be linked to seriouswhole body diseases/conditions, they would rather be examined for periodontal disease instead ofhaving their teeth cleaned at their next visit to the dentist’s office.Adapted from Hein C et al. Presented at 83 rd Annual Session of the American Dental Hygienists’ Association;Orlando, Florida; June 2006. 35systemic implication of perio dontaldisease.4. There are numerous sources of informationavailable for educating patientsin oral-systemic health, includingwebsites designed for direct accessof consumer-patients and printed materialssupplied by professional organizations that can be disseminatedby healthcare practitioners.DEVELOPING EFFECTIVECOMMUNICATION WITH PATIENTSABOUT ORAL-SYSTEMIC HEALTHThe American Dental Association (ADA)Weighs in on Oral Health LiteracyThe ADA has defined oral health literacyas “the degree to which individuals havethe capacity to obtain, process, and understandbasic health information and servicesneeded to make appropriate oral health decisions.”3 It is recognized that people withlow oral health literacy are often less likelyto seek preventive care, comply with prescribedtreatment, and maintain self-care regimens;as such, limited oral health literacy isa potential barrier to effective prevention,diagnosis, and treatment of oral disease. 3Addressing Oral Health LiteracyWithin the Dental and DentalHygiene ProfessionsIn a 2004 National Institutes of Medicinereport, it was estimated that 90 millionadult Americans have difficulty in obtaining,processing, and understanding basic healthinformation and services needed to make appropriatehealth decisions. 1 This calls attentionto the importance of healthcare providers

294 Periodontal Disease and Overall Health: A Clinician's GuideFigure 2. Patient Education Article About Periodontal Disease Published by theFigure 2. Journal of the American Medical Association.As a public service of JAMA, the organization has permitted the article to be photocopiednoncommercially by physicians and other healthcare professionals to share with patients.Reprinted with permission from Torpy JM, Burke AE, Glass RM. JAMA 2008;299:5. 36to improve their communications skills anddeliver patient education in such a way thatit can be readily understood and acted uponby patients.Given such strong data that suggest patientsunderstand the correlation between oraland systemic health, it seems reasonable to assumethat dental providers are conveying and

Chapter 18Chapter 18 The Role of the Professional in Educating the Public About the Importance of Oral Health 295reinforcing this information. However, evidencethat dental practitioners are doing anadequate job in educating their patients isnot readily apparent when searching the professionalliterature, or reviewing survey datagenerated by professional organizations. Althoughmore than 75% of 1,000 subjects ina randomly selected, nationally representativesurvey of US adults believe oral healthis integral to overall health, it is disconcertingto find that in the same survey, only 51%responded that their dentist discussed the relationshipbetween oral and overall health. 34It has been estimated that 33% of dentalpatients may not know that periodontaldisease needs to be treated and should not beleft alone; 2 another 33% believe that a littlebleeding from brushing is normal. 2 While83% of US adults may say their dentist istheir primary source of information on oralcare practices, a significant portion of theseadults also report that they have not discussedtheir oral health issues with a dentalprofessional. 2 This is especially troublingwhen considering that more than half ofthe adults living in the US experience oneor more oral health conditions. 2These types of responses from consumer-patientsmirror the disturbing findingsreported by various researchers whenthey studied dental providers’ track recordsin providing smoking cessation counseling.For instance, it has been estimated that only30%–50% of dentists and 25% of dentalhygienists in the US ask their patients aboutsmoking, 37,38 and the cessation advice providedin dental offices has been described as“rather ad hoc and somewhat superficial.” 39Another study found that when comparingtobacco-use cessation services provided byvarious types of healthcare providers, interventionsby dental providers ranked lowest(compared with physicians, mental healthcounselors, and social workers) in terms ofboth quantity and quality of services. 40 Lackof training and incentives were most oftencited to explain the reluctance of dentistsand dental hygienists to provide tobacco cessationinterventions. 41Dismantling the Hurdles toEffectively Educate PatientsAbout Oral-Systemic HealthBy virtue of the frequency by whichpeople visit dentists for checkups and routineprophylaxis, dentists and dental hygienistsare in a unique position to deliver a pivotallyimportant message to patients about oralsystemichealth. However, this opportunity isoften forfeited. One of the greatest hurdles toeffectively communicating informationabout issues related to oral-systemic health isthat dentists are often reluctant to discuss issuesthat patients may perceive as unpopular.However, evidence that patients are concernedabout periodontal disease suggeststhat the opposite may be true. 34,35 Some dentistsmay believe that their involvement ingreater systemic sequelae of oral infectionsand inflammation falls beyond their scope ofpractice. However, data suggest a growingtrend that patients are starting to view dentistsas overall healthcare providers. 34 Accordingly,it is crucial that dentists lead thecharge in conveying to patients the importanceof maintaining both oral and overallhealth. 34 Other hurdles associated with effectivelycommunicating important informationabout oral-systemic health includethe barriers listed below.Lack of Training in Oral-Systemic ScienceOral-systemic science may not havebeen emphasized during a dentist’s or dentalhygienist’s formal education and training.Many are unclear about the credibility of thescience or strength of evidence; others areuncertain about the etiological mechanismsthat have been implicated in many oral-systemicrelationships and are uncomfortablewith how these inter-relationships should beexplained to patients.

296 Periodontal Disease and Overall Health: A Clinician's GuideOrganized dentistry has recently takenon the monumental task of planning for educationalreform, much of which is related torevision of curricula to include more comprehensiveeducation in oral-systemic relationships,immunology, genetics, and molecularbiology. 21,42-44 For professionals already inpractice, there exists numerous opportunitiesfor continuing education in oral-systemicscience, and a routinely conducted literaturesearch of studies related to oral-systemic relationships,that includes both medical anddental journals, will provide practitioners withthe most up-to-date information.Ineffective Communication SkillsA dentist or dental hygienist may haveinadequate communication skills.Practitioner-to-patient counseling is themost effective way to increase a consumerpatients’understanding of the significanceof oral health, assuming practitioners haveadequate communication skills. It is unclearwhether or not patients believe their dentistsare as concerned with their overall healthas they are with their oral health. 34 As such,dentists and dental hygienists must start toconsider the liability associated with a limitedview of their responsibility to ensurepatients’ oral-systemic health, become pro -active in advocating for comprehensiveeducation of patients, and master effectivecommunication skills.The first step to increasing patients’ understandingof oral-systemic relationships isto provide the right kind of training to ensurethat all the members of the dental team areable to effectively communicate key messagesrelated to oral-systemic health, and beprepared to appropriately answer patients’questions. The ADA has passed a resolutionto seek external funding to support the designand execution of a comprehensive oralhealth literacy awareness and education strategytargeting the entire dental team. 3 A relatedresolution encourages the developmentof oral health literacy continuing educationprograms to train dentists and allied dentalteam members to communicate effectivelywith patients who have limited literacy skills. 3Scheduling LimitationsScheduling often does not allow fortime to counsel patients; likewise, there areno incentive or reimbursement mechanismsavailable for patient education/counseling.Regardless of whether or not there is anincentive to educate and counsel patients,dental providers are increasingly expectedto perform these important services. A surveyof the public’s perception of dentistry indicatesthat consumer-patients may see thedentist’s role as much larger than the practicingdentist sees it, and that patients maysee their dentist more as a physician thandentists themselves do. 34 Patients expect dentiststo discuss serious health issues they mightbe confronting and not just discuss the traditionalexpectations of dental services. 34A well-recognized practice managementexpert 45 noted that compared to previousdecades, more dental patients are “shoppingaround” for dental care and changing dentalpractices. More comprehensive service offeringswas cited as an important factor inpatients’ selection of dentists, and deliveringexceptional customer service, advocating patienteducation, and developing customizedhome care regimens were cited as key indeveloping long-term patient retention. Theauthor concluded, “By demonstrating astrong commitment to customer service, education,and home care, patients recognizethat oral healthcare pro viders are interested intheir well-being rather than simply treatingproblems.” 45 It seems clear that the publicwants a different approach to dental care,and those practitioners who provide effectivepatient education and risk counselingservices will be well positioned to grow theirpractices, even during economically challengingtimes.

Chapter 18Chapter 18 The Role of the Professional in Educating the Public About the Importance of Oral Health 297Summary Points1. Because of a profound limitation inoral health literacy within the US, alarge portion of the public is not ableto obtain, process, and make appropriatedecisions about their oralhealth. This disparity contributes toavoidable healthcare spending in themagnitude of billions of dollars eachyear. The American Dental Associationrecognizes the severity of thelack of oral health literacy in the USand is taking steps to address thisdisparity.2. It is unclear whether or not the majorityof dentists and dental hygienistsare proactively educating patientsabout the relationship between oraland systemic health; however, this isan important factor to consider in determiningwhy oral health literacy isso limited within the US.3. There are a number of hurdles thatprevent dental practitioners from effectivelycommunicating informationabout issues related to oral-systemichealth. Dentists and dental hygienistsmust address issues related to inadequateeducation in oral-systemic relationships,philosophies of practicethat may be outdated or preclude providingthis level of patient education,and concerns relative to the lack ofcompensation related to providingpatient education. Failure to providepatient education services has bothethical and legal implications.KEY AND CREDIBLEINFORMATION TO COMMUNICATETO PATIENTS ABOUT THE LINKBETWEEN PERIODONTAL DISEASEAND SYSTEMIC DISEASESInformation about the relationshipbetween oral and systemic health originatesfrom numerous sources, including consumerpublications, television, radio, continuingeducation programs, and insurance industrycampaigns. Other important sources of informationinclude professional and not-forprofitorganizations, such as the AmericanAcademy of Periodontology and the AmericanDiabetes Association, as well as fromhealth professionals and industries marketingoral care products. It should be noted that thesource that patients often put the greatestweight on is information coming from theirdentist or dental hygienist. It is therefore ofprime importance that the dental communityand dental paraprofessionals stay currentwith emerging research about oral-systemicconnections. Oral health professionals areresponsible for filtering second-hand sourcesof information on oral-systemic health(sources other than well-respected scientificliterature) to ensure that what is communicatedto patients is scientifically sound.The process of professional developmentthat will prepare individual dentistsand dental hygienists to become authoritativeexperts in the evidence of oral-systemic relationshipsis illustrated in Figure 3. As practitionersproceed through this process—fromsurveillance to clinical application and publicoutreach—confidence in how to communicatethis information to patients becomes anatural by-product of the self-learning thatoccurs throughout the process.Key and Credible Sound Bitesfor Patient EducationWhat evidence of oral-systemic relationshipsshould we confidently communicateto patients? The following statements,communicated in layman’s terms, are wellsupported by scientific evidence, and easilyunderstood by patients. These statementsprovide an explanation of the potential forperiodontal pathogens and their endotoxinsto gain access to the vasculature and inciteinflammation and a cascade of pathologicalevents in distant organs. This information is

298 Periodontal Disease and Overall Health: A Clinician's GuideFigure 3. The Process of Ensuring Scientific Integrity of Information Related toFigure 3. Oral-Systemic Relationships and Appropriate Integration into Patient Education,Figure 3. Clinical Practice, and Public Outreach Activities to Increase Nondental HealthcareFigure 3. Providers’ and Consumer-Patients’ Awareness of the Importance of Oral Health.applicable when describing the etiologicalmechanisms that have been implicated inmost of the oral-systemic relationships underinvestigation. Each involve describing theinter-relationship between the following:Periodontal Infection andSystemic Inflammation• Today we know that infection fromgum disease is not contained simplywithin the oral cavity.• Bacteria from gum infection causeinflammation.• Bacteria and their products enter theblood stream from the gum pockets,leading to systemic inflammation.• Bacteria and toxins from gum diseasecan move through blood vesselsto distant sites in the body, includingthe heart, kidneys, lungs, brain, anddeveloping fetuses in infected pregnantwomen.• This inflammatory process has beenlinked to a number of serious diseasesand conditions such as heartdisease, stroke, pneumonia, pretermbirth of low birth weight babies, complicationsof diabetes, and chronickidney disease. It is therefore importantthat any potential source of infectionand inflammation be treated.• Gum disease (periodontal disease) isan often overlooked source of infectionand inflammation and it is veryimportant that patients be examined.If gum disease is diagnosed, it mustbe treated to reduce the risk for systemicinflammation that is associatedwith many of these diseases andconditions.Diabetes and Periodontal Disease• Diabetes increases the risk of infectionfrom any source. Gum disease isan infection and a complication ofdiabetes that is often unrecognized.• People with poorly controlled diabetesare much more susceptible togum disease and may be two tofour times more likely to developgum disease than people withoutdiabetes.

Chapter 18Chapter 18 The Role of the Professional in Educating the Public About the Importance of Oral Health 299• The presence of gum disease increasesthe risk of worsening glycemiccontrol over time.• Research suggests gum diseasecauses inflammation throughout thebody, making it more difficult for patientswith diabetes to utilize insulin.This may cause hyperglycemia andmake it difficult for patients and theirphysicians to regulate blood sugarlevels. This increases the risk forcoronary heart disease.• Good glycemic control, an HbA1cvalue of less than 6% for most patients,significantly reduces the risk for theserious complications of diabetes, includinggum disease.• Although more research needs to beconducted, studies that have measuredthe difference in HbA1c aftertreatment of gum disease report improvementsin blood glucose controlover time.• Patients with poor blood sugar controlmay have more rapid recurrence of deeppockets and less favorable long-termresponse to treatment of gum disease.• When gum disease goes untreated inpatients with diabetes, they are put atgreater risk for developing long-termcomplications associated with diabetes,such as CVD and kidney disease.• Patients should be counseled to complywith their healthcare provider’srecommendations for HbA1c testingat least every three months, and to requestthat physicians forward copiesof test results to their dentists. Thisallows the dental provider to monitorblood sugar levels and the health oftheir patients’ gums.Periodontal Disease and Increased Riskfor CVD• Accumulated evidence suggests thatindividuals with gum disease mayhave a moderately increased risk forcoronary heart disease and stroke.• It is important to identify those individualswho may be at greater riskfor heart disease or stroke and whohave gum disease.• It is important to understand how gumdisease and increased risk for heartdisease and stroke may be related.• When there is inflammation withinheart tissues, arteries become lesselastic while the lumen of affectedarteries become narrower and morerestricted.• When arteries become more narrowed,blood clots may form andsmall particles of clots may breakoff, accumulate, and clog arteries,impeding blood flow. This can resultin a heart attack, stroke, or pulmonaryembolism, depending on thelocation of the blood clot.• It is known that damage from infectionand inflammation can accumulateover a lifetime, increasing the cumulativerisk for heart disease and stroke.• There is some early evidence suggestingthat treatment of gum diseasemay improve the flow of bloodto the coronary arteries; however,more research is needed before it isknown for certain how gum treatmentaffects the heart. In the meantime,the American Academy ofPerio dontology has determined thattreatment of gum disease may preventthe onset or progression of athero -sclerosis-induced diseases.Periodontal Disease and Increased Riskfor Adverse Pregnancy Outcomes• Infection from any source increasesthe risk of complications during pregnancy.Gum disease may be one of theinfections that poses a threat to healthypregnancy.

300 Periodontal Disease and Overall Health: A Clinician's Guide• It is estimated that approximately40% of pregnant women have someform of gum disease.• Evidence suggests that in some populations,pregnant women who havegum disease may be at two- to fivetimesgreater risk for various pregnancycomplications, including pre -term birth, pre-eclampsia, gestationaldiabetes, and delivery of low birthweight infants.• Now that oral healthcare providersand obstetricians recognize theremight be a link between inflammationin the body and problems duringpregnancy, the goal is to eliminateall oral inflammation before and duringpregnancy.• Oral health before and during pregnancymay be important for preventingadverse pregnancy events, however,this has yet to be well established.• Research has confirmed that gumtreatment during pregnancy is safeand improves maternal oral health.Periodontal Disease and Increased Riskfor Respiratory Infection• Research suggests that institutionalizedelderly people and patients inintensive care units who have poororal hygiene may be at greater riskfor pneumonia and other respiratoryinfections.• Oral pharyngeal surfaces, includingthe teeth, can serve as a reservoir forpathogenic bacteria that are known tocause pneumonia. These bacteria canbe aspirated into the lungs wherethey may cause respiratory infections—many of which can be fatal.• Respiratory infections related to poororal hygiene in institutionalized pa -tients in intensive care units and nursinghomes can be reduced by effectiveoral plaque control measures.• Cytokines are a type of chemical normallyproduced by the body to defenditself against inflammation.When produced in gum tissue as a resultof infection, cytokines may causeinflammation of the lower respiratoryairway following aspiration ofbacteria known to cause pneumonia.This causes the lining of the airwaysto become more vulnerable to invadingbacteria. Therefore, it is importantto identify elderly individualswho may be at greater risk for respiratoryproblems because of undiagnosedand untreated gum disease.General Advice to Patients• It has become increasingly clear thatprevention, diagnosis, and treatmentof periodontal disease are very importantin maintaining overall healthduring the aging process.• Patients should be advised to come toeach dental appointment with an upto-datelist of prescribed and over-thecountermedications they are taking sothe dentist or dental hygienist can beaware of any agents that may affectthe oral cavity or be a contraindicationfor certain types of dental treatment.• Up-to-date information regarding thestatus of the patient’s overall systemichealth needs to be related tothe oral healthcare provider.• Patients need to be counseled to provideinformation about oral health—especially when gum disease has beendiagnosed—to their other medicalproviders.• Oral healthcare providers should continuallyreinforce good oral hygieneand home care. Inclusion of an antibacterialtoothpaste or mouth rinsein the home care regimen can helpreduce dental plaque build-up andgingivitis.

Chapter 18Chapter 18 The Role of the Professional in Educating the Public About the Importance of Oral Health 301Summary PointsNot only do oral healthcare providershave an ethical obligation to educate patientson the relationship between oral health andgeneral health, dentists and dental hygienistsare responsible for ensuring that what iscommunicated to patients and the public atlarge is scientifically supported.1. Given the increasing preponderanceof evidence about oral-systemic relationshipsgenerated from second-handsources, the task of ensuring scientificintegrity of information can bechallenging. If practitioners systemizethe process of updating their knowledgebase through reading peerreviewedarticles on a routine basis,this will provide an excellent screenthrough which to filter informationfrom the domain of second-hand, oftenunreliable, sources of information.2. Although there is much that is still inconclusiveabout certain oral-systemicrelationships, there does exist sufficientevidence of the relationship betweenperiodontal disease and its rolein amplifying systemic inflammationand increased risk for heart disease,stroke, adverse pregnancy outcomes,complications of diabetes, and increasedrisk for respiratory infectionsin institutionalized patients. Effectivecommunication of this information isa responsibility of all dentists anddental hygienists.OUTREACH ACTIVITIES TOINFLUENCE THE PUBLIC’SPERCEPTION OF THEIMPORTANCE OF ORAL HEALTHThe number of things that dentists anddental hygienists can do to reach out to thecommunity to create greater awareness of oralsystemichealth is limited only by individualinitiative and a commitment to change theperceptions of nondental healthcare providersand the public regarding the importance oforal health. Table 1 lists a number of outreachactivities that oral healthcare providers havereported as being successful in increasing theawareness of oral-systemic relationships inphysician communities and the public at large.Beyond the practice setting, dentistsand dental hygienists have the opportunity toengage in novel outreach activities that havethe potential to increase awareness of perio -dontal-systemic relationships. These typesof endeavors are valuable in bringing aboutimprovement in oral health literacy and theyprovide excellent opportunities for practitionersto build interpersonal collaborationand enhance their practices.CONCLUSIONSOral diseases are an often overlookedsource of infection that have the potential toTable 1. Outreach Activities for Dental Professionals to Influence Nondental Healthcare Providers’Table 1. .and the Public’s Perception of the Importance of Oral Health Outside the Practice Setting• Volunteer to deliver a presentation at the local hospital’s rounds• Take physicians and nurses to lunch to discuss building a collaborative relationship and systems of triage• Routinely visit physicians’ offices to supply educational materials for patients• Dental hygiene organizations may partner with nursing organizations to conduct a health fair in whichnurses screen for oral diseases/conditions, and hygienists screen for CVD and diabetes• Volunteer to present information at local meetings of civic organizations, hospital programs for the public,churches, etc.• Volunteer to write a column about oral-systemic relationships in community newspapers• Invite medical colleagues to a study club when information on oral-systemic medicine is being presented• Provide volunteer in-service training in oral healthcare for nursing assistants at nursing home facilities• Use referral letters to simultaneously educate physicians about oral-systemic relationships

302 Periodontal Disease and Overall Health: A Clinician's Guidecompromise overall health, especially in individualswho have an amplified inflammatoryresponse to bacterial infections such asperiodontal disease. Evidence to support arelationship between periodontal disease andincreased risk for heart disease, stroke, worsenedglycemic control in individuals withdiabetes, adverse pregnancy outcomes, respiratoryconditions, chronic kidney disease,and complications of diabetes is emerging asa relatively new body of knowledge thatdental and dental hygiene professionals areethically bound to share with their patients.Mainstream media, university- and governmental-sponsoredpublic health outreach,insurance industry campaigns, professionaland nonprofit organizations, nondentalhealthcare practitioners and commercial advertisingassociated with oral care productshave contributed greatly to increasing oralhealthcare literacy. However, it must be recognizedthat second-hand information aboutoral-systemic health must be filtered by practitionersto ensure that what is being communicatedto patients and the public at largeis scientifically supported.Lack of health literacy has been cited asa significant factor in undermining the effec -tiveness of our current healthcare deliverysystem, and may account for billions ofdollars in added healthcare costs each year.There are a number of reasons why dentalproviders may be reluctant to become involvedwith counseling patients about oralsystemichealth. However, given the strengthof evidence that supports inter-relationshipsbetween oral diseases and systemic sequelae,providing effective patient education programsis no longer optional.Beyond practice-based patient educationstrategies, forward thinking oral healthcareproviders must pursue opportunities toincrease the awareness of the importance oforal health within nondental healthcareprovider communities and the consumerpublic. Consumer-patients are increasinglyexpecting dental practitioners to reconnectthe mouth to the rest of the body, and are anticipatingthat dentists and dental hygienistswill move beyond a preoccupation with providingtraditional dental procedures exclusively.Finally, if dentists, dental hygienists,and nondental providers are effective in communicatinghow integral oral health is to overallhealth, this heightened oral health literacymay prompt changes in public policy.Supplemental ReadingsAmerican Academy of Periodontology. Parameter onSystemic Conditions Affected by Periodontal Diseases.J Periodontol 2000;71:880–883. http://perio.org/resourcesproducts/pdf/880.pdf.Mealey BL, Oates TW. Diabetes Mellitus and Perio -dontal Disease. J Periodontol 2006;77:1289–1303.http://perio.org/resources-products/pdf/lr-diabetes.pdf.Friedewald VE, Kornman KS, Beck JD, et al. TheAmerican Journal of Cardiology and Journal of Perio -dontology Editors’ Consensus: Periodontitis and Athero -sclerotic Cardiovascular Disease. J Periodontol 2009;Vol. 80, No. 7, Pages 1021–1032. http://www.joponline.org/doi/pdf/10.1902/jop.2009.097001?cookieSet=1.Hein C, Cobb C, Iacopino A. Report of the IndependentPanel of Experts of ‘The Scottsdale Project’. Publishedas a Special Supplement to Grand Rounds in Oral-Sys Med 2007;3. Access through www.caseyhein.com.Hein C. Proceedings and consensus opinion from theglo bal oral and systemic health summit; present evidenceand future directions. Grand Rounds in Oral-Sys Med2007;(Suppl):1. Access through www.caseyhein.com.REFERENCES1. Nielsen-Bohlman L, Panzer AM, Kindig DA, eds.Health Literacy: A Prescription to End Confusion.National Institutes of Medicine, Washington, DC,National Academies Press, 2004.2. American Dental Association. The public speaks upon oral health care. October 2008. Available athttp://ada.org/public/media/presskits/publicspeaks/index.asp.Accessed October 8, 2009.3. Crozier S. ADA House passes resolutions on oralhealth literacy. Available at http://www.ada.org/prof/resources/pubs/adanews/adanewsarticle.asp?articleid=2236. Accessed October 8, 2009.4. US Department of Health and Human Services.

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J Periodontol 2002;73:911–924.9. López NJ, DaSilva I, Ipinza J, Gutiérrez J. Perio -dontal therapy reduces the rate of preterm low birthweight in women with pregnancy-associated gingivitis.J Perio dontol 2005;76(Suppl):2144–2153.10. Michalowicz BS, Hodges JS, DiAngelis AJ, LupoVR, Novak MJ, Ferguson JE, Buchanan W, BofillJ, Papapanou PN, Mitchell DA, Matseoane S,Tschida PA. Treatment of periodontal disease andthe risk of preterm birth. N Engl J Med 2006;355:1885–1894.11. Tonetti M, D’Aiuto F, Nibali L, Donald A, StorryC, Parkar M, Suvan J, Hingorani AD, Vallance P,Deanfield J. Treatment of periodontitis and endo -thelial function. N Engl J Med 2007;356:911–920.12. Elter JR, Hinderliter AL, Offenbacher S, Beck JD,Caughey M, Brodala N, Madianos PN. The effectsof periodontal therapy on vascular endothelial function:a pilot trial. Am Heart J 2006;151:47.13. D’Aiuto F, Parkar M, Tonetti MS. Acute effects ofperiodontal therapy on bio-markers of vascularhealth. 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Renowned clinicians and scientists worldwide have studied therelationship of periodontal disease to overall health and disease.We are fortunate to have assembled such a respected and scholarlybody of contributors who, in eighteen chapters, provide a currentand thoughtful perspective on this relationship.—Robert J. Genco, Ray C. Williams