Periodontal Disease and Overall Health: A Clinician's Guide

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CHAPTER 2 Overview of Periodontal Disease:CHAPTER 2 Causes, Pathogenesis, and Characteristics 19dazole can be used to treat acute necrotizingulcerative gingivitis (NUG), 52 and metronidazole/amoxicillincombination therapy canbe used to treat aggressive adolescent periodontitisassociated with A. actinomycetemcomitans.53 Systemic antibiotic therapy hasthe advantage of simple, easy administrationof drugs to multiple periodontal sites. However,patient compliance needs to be considered,inability to achieve adequate concentrationsat the site of infection, adverse drugreactions, and the develop ment of antibioticresistance can be issues. 54 Common antibiotictherapies for the treatment of periodontitisinclude metronidazole, clindamycin, doxycyclineor minocycline, ciprofloxacin,azithromycin, metronidazole/amoxicillin,and metronidazole/cipro floxacin. 55 For adultpatients with acute periodontal abscesses,amoxicillin is used as an adjunct to incisionand drainage. For patients with allergies tobeta-lactam drugs (e.g., amoxicillin), azith -romycin or clindamycin would be the choice.Researchers have shown that periodontaltreatment can benefit some systemic diseasesknown to be associated with periodontitis,such as diabetes and preterm delivery.Grossi and colleagues reported that diabeticpatients receiving scaling and root planingwith systemic doxycycline showed significantreductions in mean HbA1c. 56 Effectivetreatment of periodontal infection and reduc -tion of periodontal inflammation is associatedwith a reduction in levels of glycatedhemo globin. Clothier and colleagues alsoshowed that performing scaling and root planingin pregnant women with periodontitismay reduce preterm delivery. 57 However, ad -junc tive metronidazole therapy did not im -prove pregnancy outcomes. Two recent studieshave not shown improvements in adversepregnancy outcomes with scaling and rootplaning. 58 However, the level of perio dontaltreatment provided may have been veryinadequate. More studies are needed in thisfield to determine the effect of periodontaltreatment on the outcomes of adverse pregnancyand the extent of therapy that mayneed to be provided in order to have a significantimpact.Host-Modulation TherapyBacteria and the host are two essentialfactors to the development of periodontitis.Reduction of bacterial load is the con -ventional approach for the management ofperiodontal diseases. More recently, periodontaltreatment strategies have includedhost-modulation therapy as an adjunctivetreatment option. Host-modulation therapy istreating the host response to either reduce theexcess production of cytokines and destructiveenzymes so there is less damage to theperiodontal tissues, or to stimulate the regenerative process, allowing for the restorationof connective tissue attachment andbone formation to occur.Host modulation was first introduced todentistry by Williams 59 and Golub and colleagues.60 Williams stated: “There are compellingdata from studies in animals and humantrials indicating that pharmacologicagents that modulate the host responses believedto be involved in the pathogenesis ofperiodontal destruction may be efficacious inslowing the progression of periodontitis.” 59Golub and colleagues discussed “host modulationwith tetracyclines and their chemicallymodified analogues.” 60 A variety of differentdrug classes have been evaluated ashost-modulation agents, including the non -steroidal anti-inflammatory drugs, bisphosphonates,tetracyclines (Figure 4), 36 enamelmatrix proteins, growth factors, and bonemorphogenetic proteins.Systemically Administered AgentsSubantimicrobial-Dose DoxycyclineSubantimicrobial-dose doxycycline (SDD)is the only FDA-approved MMP inhibitorand systemic host-modulation therapy for the
20 Periodontal Disease and Overall Health: A Clinician's GuideFigure 4. Potential Adjunctive Therapeutic ApproachesAntimicrobialsBacterialproductsHostcellsNSAIDSPeriostatProstaglandinsCytokines(IL-1, IL-6, TNF)MMPsPeriostatBisphosphonatesPeriostatOsteoclastsBoneresorptionConnectivetissuebreakdownPocketsandCALToothmobilityandkissBacterialcomponent+ Host response component= ClinicalsequelaeSource: Carranza’s Clinical Periodontology, 10th Ed. WB Saunders Company; 2006:275–282. 36 Reproducedwith permission.management of periodontitis. SDD is a 20-mgdose of doxycycline (Periostat ® ) taken twicedaily for three months and used in multicenterclinical trials for up to a maximum of 24months of continuous dosing. SDD is used asan adjunct to scaling and root planing in thetreatment of CP. The host-modulation effectsof SDD include enzyme inhibition, cytokinereductions, and effects on osteoclast function.Since perio dontitis is associated with manysystemic diseases (e.g., osteoporosis, diabetes,cardiovascular disease), researchers have investigatedthe effect of SDD on these system -ic conditions. Studies have shown that SDD:• Can effectively reduce the levels oflocalized and systemic inflammatorymediators in osteopenic patients, inaddition to improving on the clinicalmeasurements of periodontitis 61• Has been shown to reduce systemicinflammatory biomarkers in CVDpatients 62• Decreases HbA1c in patients whoare taking normally prescribed hypoglycemicagents 63The impact of SDD therapy on periodontitismay be amplified by an independentbenefit for other inflammatory diseases;additional studies are being conducted to investigatethe impact of this host-modulationtherapy.Locally Administered AgentsEnamel Matrix Proteins, Growth Factors,and Bone Morphogenetic ProteinsA number of local host-modulationagents have been investigated for potentialuse as adjuncts to surgical procedures to improveperiodontal health. These have includedenamel matrix proteins (Emdogain ® ),bone morphogenetic proteins, and plateletderivedgrowth factors (PDGF). The initiallocal host-modulation agent approved by theFDA for adjunctive use during surgery toassist with clinical attachment gain andwound healing was Emdogain; this has beenfollowed by PDGF combined with a resorbablesynthetic bone matrix growth-factorenhanced matrix (GEM 21S) to assist in
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