Guided Tissue Regeneration for the Treatment of … articles...included review of relevant bibliographies. Two manufacturers of GTR devices were contacted regarding unpub-lished data

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Guided Tissue Regeneration for the Treatmentof Periodontal Intrabony and Furcation Defects.

A Systematic ReviewKevin G. Murphy* and John C. Gunsolley†

*Private practice, Baltimore, Maryland.† Department of Periodontics, College of Dental Surgery, University of Maryland, Baltimore.

Background: Many clinical studies have demonstrated that guided tissue regeneration (GTR) is a suc-cessful treatment modality of periodontal reconstructive surgery and it has become an accepted procedurein most periodontal practices.

Rationale: The purpose of this structured review was to assess the efficacy of guided tissue regenera-tion (GTR) procedures in patients with periodontal osseous defects compared with surgical controls onclinical, radiographic, adverse, and patient-centered outcomes. It extends the scope of previous GTR sys-tematic reviews, which were limited to randomized controlled studies, by the scope of outcome measuresexamined, and the duration of the study.

Focused Question: In patients with periodontal osseous defects, what is the effect of physical barrierscompared with surgical controls on clinical, radiographic, adverse, and patient-centered outcomes?

Search Protocol: An electronic search of the Cochrane Oral Health Group Trials Register and MEDLINEdatabases was performed. Manual searching of journals included Journal of Clinical Periodontology, Jour-nal of Periodontology, and Journal of Periodontal Research up to January 2002. This manual search alsoincluded review of relevant bibliographies. Two manufacturers of GTR devices were contacted regarding unpub-lished data.

Selection CriteriaInclusion criteria: Studies were selected for review if the evidence level was 3B (cohort) or above, at least

6 months duration, and compared a test GTR intervention with a surgical control.Exclusion criteria: Studies with experimental design problems; histologic or microbiological investigations;

or those with outcome measurements, study populations, or study duration not consistent with the inclu-sion criteria were excluded.

Primary outcome measures for intrabony defects were: clinical attachment level (CAL) gain, probingdepth reduction (PD), gingival recession (REC) reduction; for furcation defects: vertical probing attachmentlevel (VPAL) gain, vertical probing depth reduction (VPD), horizontal probing depth reduction (HPD), hor-izontal open probing attachment level gain (HOPA), and vertical open probing attachment level gain (VOPA).Meta-analysis was performed to compare GTR procedures to other surgical treatments and to examine theresulting clinical outcomes.

Main Results1. For the primary outcome variables, in both intrabony-defect and furcation-defect studies, GTR was

favored over open flap debridement (OFD) therapies (P <0.0001).2. No differences were detected among barrier types, but barrier types could explain some heterogene-

ity in the results.3. Augmentation of the GTR barrier with a particulate graft enhanced VPD (P <0.05), VPAL, and HOPA,

but none of the intrabony outcomes.Reviewer’s Conclusions: Overall, GTR is consistently more effective than OFD in the gain of clinical

attachment and probing depth reduction in the treatment of intrabony and furcation defects.Ann Periodontol 2003;8:266-302.

KEY WORDSComparative studies; guided tissue regeneration; outcomes assessment; membranes, barrier;periodontal diseases/surgery; review literature; surgical flaps; meta-analysis.

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Many clinical studies have demonstrated thatguided tissue regeneration (GTR) is a success-ful treatment modality of periodontal recon-

structive surgery. The GTR technique delays the apicalmigration of the gingival epithelium by excluding thegingival connective tissue and allows granulation tissuederived from the periodontal ligament and osseous tis-sues to repopulate the space adjacent to the denudedroot surface. Several human biopsy GTR studies havedocumented new attachment resulting in new connec-tive tissue attachment and bone fill.1-3 Early proof-of-principle studies also demonstrated that GTR proceduresresulted in the improvement of clinical measures.4-7

However, patient-centered outcomes, such as patientcomfort, long-term tooth retention, dentition stability,absence of pain and esthetic appearance are seldomdiscussed in regenerative studies.8 Therefore, the sur-rogate outcomes of attachment level gain, reductionin probing depth, gingival recession, and alveolar bonechanges are considered the primary outcomes of GTRtherapies.9 This systematic review will attempt toexamine the efficacy of GTR on patient-centered andsurrogate outcomes.

The purpose of this systematic review was to assessthe efficacy of guided tissue regeneration (GTR) pro-cedures in patients with periodontal osseous defectscompared with surgical controls on clinical, radiogra-phic, adverse, and patient-centered outcomes.

FOCUSED QUESTIONIn patients with periodontal osseous defects, what is theeffect of physical barriers compared with surgical con-trols on clinical, radiographic, adverse, and patient-centered outcomes?

SEARCH PROTOCOLData Sources and Search StrategiesAn electronic search of the Cochrane Oral Health GroupTrials Register (CCTR) and MEDLINE databases wasperformed. The Journal of Clinical Periodontology, Jour-nal of Periodontology, and Journal of PeriodontalResearch, including reviews of relevant bibliographies,were manually searched up to January 2002. Two man-ufacturers of GTR devices were contacted regardingunpublished data.

The following search terms were used: (all terms usingthe “OR” operand): guided tissue regeneration, guided-tissue-regeneration, GTR, intra bony, intrabony defect;infrabony, infra bony, intra osseous, intraosseous defect,intra-osseous, furcation, furcation defect, complications,surgical complications, postoperative complications, sur-gical wound infection, and gingival recession.

Study TypesThe types of studies included for this review were: ran-domized controlled clinical studies (RCTs), systematic

reviews of RCTs, systematic reviews of cohort stud-ies, and cohort studies (CHT), systematic reviews ofcase-control studies, and case-control studies (CS).

Inclusion Criteria: Studies were limited to patientswith a diagnosis of chronic (adult) periodontitis andwho were 21 years or older. Studies examining bothintrabony and furcation defects were reviewed, butexamined separately.

All studies which included some form of the place-ment of a physical barrier membrane, designed toselectively exclude unwanted tissue from repopulatingthe periodontal wound, either as test or control inter-vention, were considered for inclusion.

Exclusion Criteria: Studies with experimental designproblems; histologic or microbiological investigations;or those with outcome measurements, study popula-tions, or study duration not consistent with the inclu-sion criteria were excluded.

ComparisonsThe following comparisons were made:

1. GTR procedures versus open flap debridement(OFD).

2. GTR procedures using a barrier plus some formof augmentation, usually a particulate bone graft, ver-sus GTR procedures using a barrier alone.

3. GTR procedures using an expanded polytetra-fluoroethylene (ePTFE) barrier versus GTR proceduresusing a bioabsorbable barrier type.

4. GTR procedures using one surgical protocol ver-sus GTR procedures using a different surgical proto-col, but the same barrier material type, based upon theflap closure technique employed.

5. GTR procedures using one postoperative recallcare regimen versus GTR procedures using a differentpostoperative recall care regimen.

OutcomesShort-term: The following clinical parameters wereevaluated by recording changes in the outcome vari-able from the time of surgery to the end of the evalu-ation period:

1. Clinical attachment level gain (CAL), measuredin both a vertical (VPAL) and horizontal (HPAL) direc-tion for furcation-defect studies.

2. Probing depth reduction (PD), measured in botha vertical (VPD) and horizontal (HPD) direction forfurcation-defect studies.

3. Gingival recession (REC) increase.4. Bone levels: assessed radiographically (X-rays)

and/or at a re-entry; (Re-entry) for intrabony-defectstudies and HOPA (horizontal) and vertical (VOPA) forfurcation-defect studies.

5. Oral hygiene efficacy and compliance utilizing full-mouth bleeding scores (FMBS) or stated oral hygieneindex.

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6. Complications related to surgical treatment (alsoa patient-centered outcome): exposure of barrier (ifapplicable), abscess formation, recession, morbidityfactor of pain.

Long-term: Long-term measurements included:1) tooth retention; 2) FMBS; and 3) disease recurrence.

Patient-centered: Patient-centered outcomes were:1) complications related to surgical treatment; 2) easeof maintenance-residual PD, defined as sites with lessthan 4 mm; and 3) esthetics, defined as REC in ante-rior teeth.

Data Collection and AnalysisThe study selection process is summarized in Figure 1.This search strategy resulted in the initial screening of

1,543 publications. These publications were entered intoa publication database manager. The abstracts of thesepublications were then obtained and reviewed. If abstracts

Figure 1.Study screening process.

Table 1.

Studies Failing to Meet Inclusion Criteria

Reference Rationale for Exclusion

Yukna10 1992; Eickholz, et al.11 2001 Data presentation errors

Windisch et al.12 2002; Teparat et al.13 1998; Dubrez et al.14 1996; Dowell et al.15 1995 Experimental design problem

Vuddhakanok et al.16 1993 Histologic investigation

Smith MacDonald et al.17 1998; Wang et al.18 1997; Chen et al.19 1997; De Sanctis et al.20 1996; MicrobiologicalMombelli et al.21 1996; Simion et al.22 1995; Frandsen et al.23 1994; Nowzari & Slots24 1994;Demolon et al.25 1993; Tempro & Nalbandian26 1993; Grevstad & Leknes27 1993; Minabe28 1991

Calongne et al.29 2001; Cortellini & Tonetti30 2001; Murphy et al.31 2000; Cortellini et al.32 1999; Case series or inadequateAguirre-Zorzano et al.33 1999; Eickholz & Hausmann34 1999; Tatakis & Trombelli35 1999; Peter et al.36 surgical controls1998; Eickholz et al.37 1998; Eickholz & Hausmann38 1998; Christgau et al.39 1997; Machtei et al.40 1995;Murphy41 1995; Froum & Tarnow42 1995; Müller & Eger43 1997; Trombelli & Scabbia44 1997;Eickholz & Hausmann45 1997; Trombelli et al.46 1997; Falk et al.47 1997; Cortellini et al.48 1996; De Sanctis et al.49

1996; Murphy50 1996; Piattelli et al.51 1996; Tonetti et al.52 1996; Nowzari et al.53 1996; Yukna & Yukna54 1996;Becker et al.55 1996; Machtei et al.56 1996; Cortellini et al.57 1996; Müller et al.58 1995; Novaes et al.59 1995;Drummond et al.60 1995; Cortellini et al.61 1995; Weigel et al.62 1995; Murphy63 1995; Anderegg et al.64 1995;Polson et al.65 1995; Cortellini et al.66 1995; Tonetti et al.67 1995; Laurell et al.68 1994; Cortellini et al.69 1994;Schallhorn & McClain70 1994; Trombelli et al.71 1994; Rosenberg & Cutler72 1994; Machtei et al.73 1994;Florès-de-Jacoby et al.74 1994; Tonetti et al.75 1993; Polson et al.76 1993; Tonetti et al.77 1993; Cortellini et al.78

1993; McClain & Schallhorn79 1993; Galgut80 1993; Mullally et al.81 1993; Al-Arrayed et al.82 1993;Selvig et al.83 1992; Gottlow et al.84 1992; Paul et al.85 1992; Stahl & Froum86 1991; Stahl & Froum3 1991;Galgut87 1990; Stahl et al.1 1990; Schallhorn & McClain5 1988; Gottlow et al.2 1986; Selvig et al.88 1993;Garrett et al.89 1988; Polson et al.90 1995; Eickholz et al.91 1996; Pontoriero et al.92 1989

Sbordone et al.93 2000; Wenzel et al.94 1992; Pontoriero et al.95 1987; Iversen et al.96 1996 Outcome measurements not consistent with this systematic review

Eickholz et al.97 2000; Karapataki et al.98,99 2000; Dörfer et al.100 2000; Trejo et al.101 1998; Chaves et al.102 Study population not1996; Sirirat et al.103 1996; Sander et al.104 1994; Stein et al.105 1993 consistent with this

systematic review (chronic periodontitis)

Sculean et al.106 2001; Christgau et al.107 1995; Twohey et al.108 1992 Study duration not consistent with this systemic review

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were not available, the full-text publications were re-viewed for appropriateness for inclusion. On basis oftitle and abstract review, the full-text publications of 192studies were obtained and evaluated for inclusion inaccordance with the protocol of this systematic review.The 103 studies excluded for failing to meet inclusioncriteria are summarized in Table 1.1-3,5,10-108 Thedatasets of studies that provided only standard errorvalues were modified by estimating the standard devi-ation values.

The selection process resulted in the inclusion of 89publications for this review.4,6,109-195 Some of thesestudies had multiple arms that were suitable for analy-sis.109,110,119,132,133,138,140,142,145,147,157,167,182 A sub-set of studies initially failed to present either standarddeviation or standard error values. These studies wereassigned a standard deviation value derived from theaverage standard deviation for the same test or controlgroup of all studies containing standard deviation values.Table 2 summarizes intrabony-defect studies that wereincluded using these assumed values.109-114 Table 3summarizes furcation-defect studies that were includedusing these assumed values.115-126 This process of stan-dard deviation value assignment resulted in the inclu-sion of an additional 18 studies for analysis.109-126

Due to the large number of publications, a relationaldatabase program was used to enter the descriptive vari-ables of the evaluated studies. Using a database formtemplate, a data abstraction form was created. Eighty-two descriptive variables and 2 surgical technique andpostoperative care rankings were gathered for each studyreviewed. Five descriptive groupings for each study weredefined: Study design, treatment protocol, subject char-

acteristics, clinical outcomes, and patient-centered out-comes. The methodological quality of the study wasassessed, examining protocol characteristics such asrandomization methods, therapist and examiner con-cealment or masking, split-mouth or parallel design, andlimitations on number of test or control sites per patient.

In addition to the criteria listed in the data abstrac-tion form, 2 procedural rankings were developed.Advanced flap management techniques are frequentlyutilized to enhance primary closure over the physicalbarrier.32,48,66,127-129 The effect of these techniqueswas examined through the development of a rankingsystem. The flap closure ranking was assigned to eachstudy as using the following criteria:

Grade 1. No attempt to cover barrier with flap or a“standard technique” wherein gingival flaps are adaptedas best possible with standard incision design and inter-rupted sutures.

Grade 2. Periosteal fenestration or split-thicknessdissection used to facilitate passive flap adaptation; inter-rupted sutures. Some form of papillae retention is used.

Grade 3. Papillae retention with some form of mat-tress suturing or specifically designed flap incision andclosure techniques such as the modified papillaepreservation technique (MPPT)129 or the simplifiedpapillae preservation technique (SPPT).32

The effect of increasing frequency of postoperativecare visit upon clinical outcomes was examined by rank-ing each study’s supportive recall program as follows:

Grade 1. No weekly care stated in protocol or woundstabilization protocol for 6 weeks or 2 or less interventionsfor the first month; longer than monthly intervals for theremainder period or 3 or more interventions for the first

Table 2.

Intrabony-Defect Studies Selected for Inclusion, Using Modified Standard Deviation Values

Intervention

Reference Design Test Control Study Ranking

Pontoriero et al.109 1999 (4-arm study) RCT EMD OFD 1B

PLA OFDPLA/PGA OFD

ePTFE OFDSculean et al.110 1999 (2-arm study) RCT EMD PLA/PGA 1B

EMD + EDTA PLA/PGAal-Arrayed et al.111 1995 RCT Hum coll OFD 3B

Orsini et al.112 2001 CHT Ca sulfate + autogeneous bone Bov coll + autogenous bone 3BQuteish & Dolby113 1992 CHT Hum coll (human) OFD 3B

Bratthall et al.114 1998 RCT PLA/PGA OFD 2B

Abbreviations: Bov coll = bovine collagen; Ca = calcium; EMD = enamel matrix proteins; ePTFE = expanded polytetrafluoroethylene; Hum coll = humancollagen; OFD = open flap debridement; PLA/PGA = polylactic/ polyglycolic acid.

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month, longer than a monthlyinterval but less than or equal toa 3-month interval for the remain-der period.

Grade 2. At least bi-weeklyfor the first 6 weeks, then everymonth thereafter.

Grade 3. Weekly for the first2 months, then bi-weekly ormonthly thereafter.

The accumulated data wereexported from the relationaldatabase to the statistical ana-lysis software. Weighted treat-ment outcomes were calculatedand expressed as weighted meandifferences. Multiple treatmentoutcomes were analyzed. Forintrabony-defect studies, CAL,PD, and REC were the primaryoutcome measures. For furcation-defect studies, VPAL, VPD, REC,VOPA, and HOPA were the pri-mary outcome measures. Hardtissue gain was also studied byexamining re-entry and x-rayoutcome measures. The statisti-cal significance of discrepanciesin the estimates of treatmentoutcomes or heterogeneity was

Table 3.

Furcation-Defect Studies Selected for Inclusion, Using Modified Standard Deviation Values

Intervention

Reference Design Test Control Study Ranking

Caton et al.115 1994 RCT PLA 910 OFD 1B

Garrett et al.116 1997 RCT PLA ePTFE 1BHugoson et al.117 1995 RCT PLA ePTFE 1B

Mehlbauer et al.118 2000 RCT PLA + PLA 910 (double barrier) + DFDBA PLA + DFDBA 1BMellonig et al.119 1994 RCT ePTFE OFD 2B

Mellonig et al. 119 1994 RCT ePTFE OFD 2BPontoriero & Lindhe120 1995* RCT ePTFE, Class II OFD 2B

Pontoriero & Lindhe121 1995* RCT ePTFE, Class III OFD 2BVan Swol et al.122 1993 RCT Bov coll OFD 2B

Vernino et al.123 1998 RCT PLA PLA 2BDemolon et al.124 1994 RCT ePTFE + amoxicillin + clavulanatic acid ePTFE 2B/3B

Garrett et al.125 1990 CHT Dura mater + DFDBA + citric acid + CPF DFDBA + citric acid + CPF 3BWallace et al.126 1994 RCT ePTFE + DFDBA ePTFE 3B

* SD and SE only shown graphically.Abbreviations: CPF = coronally positioned flap; ePTFE = expanded polytetrafluoroethylene; OFD = open flap debridement; PLA = polylactice acid; PLA/PGA =polylactic/polyglycolic acid; PLA 910 = polyglactin 910.

Table 4.

Intrabony-Defect Studies* that Provided Standard Deviation or Error Values

Intervention

Reference Design Test Control

Bichara et al.130 1999 RCT, split-mouth PLA + naproxen PLA500 mg bid

Cortellini131 1998 RCT, split-mouth PLA OFDCortellini et al.132 1995 RCT, parallel Cover of NFGT with CT CPF over NFGT

Cortellini et al.133 1996 RCT, parallel ePTFE OFDCortellini et al.133 1996 PLA OFD

Cortellini et al.132 1995 RCT, parallel ePTFE-TR OFDCortellini et al.127 2001 RCT, parallel PLA OFD

Gouldin et al.135 1996 RCT, split-mouth ePTFE + DFDBA ePTFEGuillemin et al.136 1993 RCT, split-mouth ePTFE + DFDBA ePTFE

Joly et al.137 2002 RCT, split-mouth PLA/PGA OFD

Kim et al.138 1996 RCT, parallel Ca carbonate + ePTFE Ca carbonateKim et al.138 1996

ePTFE OFDLekovic et al.139 2001 RCT, split-mouth Bov coll EMD + BPBM OFD

Sculean et al.140 2001 RCT, parallel PLA OFDSculean et al.140 2001 PLA + EMD EMD

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assessed by means of Cochran’s test for heterogeneityusing fixed- and random-effects modeling. Regressionanalysis was performed to examine the relationship ofthe flap closure technique, postoperative recall care fre-quency, and timing of barrier removal upon the out-come measures.

Ranking of StudiesOnly studies assessed to be of evidence levels lB through3B as defined by the Oxford Centre for Evidence-basedMedicine Levels of Evidence (http://cebm.jr2.ox.ac.uk/docs/levels.html) were selected for analysis. Durationof the study was not a criterion for exclusion.

DESCRIPTION OF STUDIESIntrabony DefectsTable 4 summarizes the intrabony-defect studiesselected for inclusion. Fifty-two arms from 44 studiesqualified for inclusion.6,114,130-170 Only 4 studies werecohort (CHT) designed,166,168-170 the remainder wereRCTs. Of these RCTs, 20 studies were of a split-mouthdesign. Only 20 studies used some form of conceal-ment. Eighteen studies had a length of study under 12months, but none less than 6 months. The ages of par-ticipants ranged from 21 to 84 years. Smokers were

excluded in only 2 studies, but 13 studies made someform of smoker-data subset available. There was ainconsistent definition of a smoker. Seventeen studiesused an advanced form of flap closure technique cor-relating to Grade 3. Eleven studies employed a recallcare frequency of Grade 3.

Furcation DefectsTable 5 (page 274) summarizes the furcation-defectstudies selected for inclusion.4,167,171-194 Of the quali-fying studies, only one was a CHT.193 Of the remainingRCTs, 22 were a split-mouth design. Only 6 studiesemployed examiners masked to therapy and only 2studies used therapists masked to the treatment choicebefore the barrier placement. Sixteen studies were lessthan 12 months duration, but none were less than 6months. The ages of the participants ranged from 21to 76 years. Smokers were excluded in only 2 studiesand 4 studies provided smoker subset data. Ten of thestudies described recall care frequencies of Grade 3.

MAIN RESULTSLong-Term ResultsLong-term outcome variables such as tooth loss requirethe use of long-term studies. This systematic review failed

to identify any studies meetingthe inclusion criteria which eval-uated patient outcomes for morethan 5 years. Therefore, no state-ments can be made regardingthe efficacy of periodontal ther-apy using physical barriersenhancing tooth retention.

Providing patients with a peri-odontium that is easier to main-tain is indirectly related to prob-ing depth reduction and ismanifested in post-treatmentgingival bleeding indices. As willbe discussed in detail, reductionin PD and gain in CAL as sur-rogate variables were uniformlyenhanced in GTR procedures ascompared to OFD controls. Thebleeding index utilized variedgreatly among the includedstudies, as did the evaluationinterval, making comparisonslimited. In furcation-defect stud-ies, the incidence of furcationclosure was not evaluated dueto the disparity in the definitionof what constituted completeclosure of the furcation as wellas diagnosis of the grade of thefurcation.

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Table 4. (continued)


StudyDuration Augmentation

N Study PopulationStudy

(months) Material Test Control Outcomes Ranking

9 24 24 CAL, PD, REC, re-entry 1B

12 23 23 CAL, PD, REC 1B12 14 14 VPAL, PD, REC 1B

12 12 12 CAL, PD, REC 1B12 12 12 CAL, PD, REC

12 15 15 CAL, PD, REC 1B12 55 54 CAL, PD, REC 1B

6 DFDBA 26 26 CAL, PD, REC, re-entry 1B6 DFDBA 15 15 CAL, PD, REC, re-entry 1B

8 TET roots 10 10 CAL, PD, REC, x-rays, 1Bre-entry

6 CA carbonate 14 13 CAL, PD, REC 1B

6 19 18 CAL, PD, REC 1B6 EMD + BPBM 18 18 CAL, PD, REC, re-entry 1B

12 14 14 CAL, PD, REC 1B12 EMD 14 14 CAL, PD, REC 1B(continued)

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Intrabony-Defect StudiesBarrier versus open flap debride-ment therapy. Considering allbarrier types, meta-analysis ofincluded studies demonstratedthat GTR procedures resulted ina greater gain in clinical attach-ment (CAL) when compared toOFD controls (Fig. 2, page 277;and Tables 6, page 278; and 10,page 284) at a significance levelof P <0.0001. Removing studiesin which standard deviation val-ues were assumed did not affectthis outcome. Subgroup analy-sis of the barrier type, whethercollagen-derived, ePTFE, or apolymeric bioabsorbable barrier,demonstrated that the addedbenefit of the physical barrierremains constant independent ofthe barrier type employed. Het-erogeneity among the ePTFEand polymeric groups was highlysignificant (P <0.05). This het-erogeneity became nonsignifi-cant when the 3 most efficaciousstudies within each group whereexcluded.132,133,137 When thesestudies were excluded, the treat-ment effects of using a physicalbarrier remained highly signifi-cant (P >0.0001). The differencein gain of CAL between the testbarrier types collagen, poly-meric, and ePTFE and an OFDcontrol was 0.95 ± 0.47 mm,0.92 ± 0.18, and 1.61 ± 0.25 mm,respectively.

Similar findings were demon-strated with PD reduction for allbarrier types at a significancelevel of P <0.0001 (Fig. 3, page279; Tables 7, page 280; and 10,page 284). Removing studies inwhich assumed standard devia-tion values were utilized did notaffect this outcome. Subgroupanalysis of the barrier type,whether collagen-derived, ePTFE,or a polymeric bioabsorbable bar-rier, demonstrated that the addedbenefit of the physical barrierremains constant independent ofthe barrier type employed. Het-erogeneity among the groupings

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Intervention


Tonetti et al.141 1998 RCT, parallel PLA/PGA- OFDTonetti et al.142 1996 RCT, parallel ePTFE-TR OFDTonetti et al.142 1996

ePTFE OFDTrejo et al.143 2000 RCT, parallel PLA + DFDBA PLA

Yoshinari et al.144 2001 RCT, parallel ePFTFE + minocycline ePTFEointment

Zucchelli et al.145 2002 RCT, parallel EMD ePTFEZucchelli et al.145 2002 RCT; split-mouth ePTFE-TR OFD

parallelZucchelli et al.146 1999 RCT, parallel ePTFE-TR + ePTFE-TR

metronidazole gel

Zybutz et al.147 2000 RCT, split-mouth PLA OFDZybutz et al.147 2000 ePTFE OFD

Blumenthal & Steinberg148 RCT, parallel Bov coll + DFDBA OFD1990

Camargo et al.149 2000 RCT, split-mouth Por coll + BPBM OFD

Mattson et al.150 1999 RCT, parallel Bov coll PLA/PGABenqué151 1997 CHT Bov coll (rapidly Bov coll (adult

progressive periodontitis)periodontitis)

Batista et al.152 1999 RCT, split-mouth Cellulose + HA CelluloseBratthall et al.114 1998 RCT, split-mouth PLA/PGA OFD

Chen et al.153 1995 RCT, split-mouth Bov coll + DFDBA Bov collChristgau et al.154 RCT, split-mouth PLA PLA 910

1998

Christgau et al.155 RCT, split-mouth PLA 910 ePTFE1997

Handelsman et al.6 1991 RCT ePTFE + citric acid ePTFE

Kersten et al.156 1992 RCT, split-mouth ePTFE + citric acid ePTFEKiliç et al.157 1997 RCT, parallel ePTFE OFDKiliç et al.157 1997

ePTFE + HA HAKim et al.158 1998 RCT, parallel Calcium sulfate + DFDBA OFD

Mayfield et al.159 1998 RCT, parallel PLA OFDMellado et al.160 1995 RCT, split-mouth ePTFE + DFDBA ePTFE

Paolantonio161 2002 RCT, parallel Pericardium + BPBM PericardiumPaolantonio et al.162 RCT, split-mouth Rubber dam ePTFE

1998

Weltman et al.163 1997 RCT, parallel PLA ePTFEZarkesh et al.164 1999 RCT, parallel ePTFE + TET ePTFE

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of all barriers combined and thepolymeric barriers was significantP <0.01. Again, when the 3 mostefficacious studies were removedfrom analysis, the heterogeneitybecame nonsignificant while thetreatment effect remained highlysignificant P <0.0001. The differ-ence in PD reduction betweenthe test barrier types collagen,polymeric, and ePTFE andan OFD control was 1.06 ±0.37 mm, 0.89 ± 0.14 and 1.41 ±0.20 mm, respectively.

Differences between test andcontrol groups for the amountof post-treatment recession(REC) were not significant, butusually were larger in the testgroup (Table 8, page 281; Fig.4, page 282). Both ePTFE andbioabsorbable barriers resultedin a similar amount of mild gin-gival recession. However, stud-ies that utilized some formof advanced flap managementresulted in a decrease in post-treatment recession as com-pared to OFD controls.132,133

ePTFE versus bioabsorb-able barriers. Three studiesdirectly compared the efficacyof a bioabsorbable barrier toePTFE for CAL gain. Weltmanet al.163 evaluated a polylacticacid (PLA) barrier, whereasEickholz et al.167 and Christgauet al.155 evaluated a polyglactin-910 (PLA 910) barrier (Fig. 5,page 282). Meta-analysis ofthese selected studies failed todemonstrate a significant dif-ference between ePTFE and theaforementioned polymeric bar-riers (P = 0.623). Heterogeneitywas significant at the P = 0.03level. In a similar manner to theCAL outcome, no differencesbetween ePTFE and thebioabsorbable barriers wereevident when examining PDreduction as an outcome vari-able (P = 0.272) (Fig. 6, page282) in these 3 studies.Likewise, no differences in theoutcome measure REC were

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Study Duration Augmentation




12 15 15 CAL, PD, REC 1B12 DFDBA 16 16 CAL, PD, REC, re-entry 1B

6 20 20 CAL, PD, REC 1B


12 26 26 CAL, PD, REC 1B

12 15 15 CAL, PD, REC, re-entry 1B12 14 14 CAL, PD, REC, re-entry 1B

12 DFDBA 15 15 CAL, PD, REC, re-entry 1B-2A

6 EMD + BPBM 22 22 CAL, PD, REC, re-entry 1B-2B

6 11 12 CAL, PD, REC, re-entry 1B-2B6 16 52 CAL, PD, REC 2A-3B

6 Bovine-derived HA 13 13 CAL, PD, REC, re-entry 2B12 11 11 CAL, PD, REC 2B

6 DFDBA 7 8 CAL, PD, REC 2B12 25 25 CAL, PD, REC, x-rays 2B

12 10 10 CAL, PD, REC 2B

9 9 9 CAL, PD, REC, re-entry 2B

12 14 12 CAL, PD, REC 2B6 HA + type I bov coll 10 10 CAL, PD, REC, x-rays 2B

6 HA + type I bov coll 10 10 CAL, PD, REC, x-rays12 Calcium sulfate + 13 13 CAL, PD, REC 2B

DFDBA (matrix is also aug)

12 10 11 CAL, PD, REC, re-entry 2BDFDBA 11 11 CAL, re-entry 2B

12 BPBM 17 17 CAL, PD, REC, re-entry 2B12 22 22 CAL, PD, REC, x-rays 2B

12 16 14 CAL, PD, REC, re-entry 2B12 ePTFE + TET 11 11 CAL, re-entry 2B

(continued)

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detected in studies directly com-paring ePTFE to a bioabsorbablebarrier (Fig. 7, page 283).

Barrier versus barrier plusaugmentation material. Sevenstudies examined the effect ofthe addition of an augmenta-tion material under the physi-cal barrier (Fig. 8, page283).135,136,143,152,153,160,161

All studies used a form of partic-ulate bone graft, with demineral-ized freeze-dried bone allograft(DFDBA) selected in 5 of the7 studies. The control interven-tion was the barrier alone whilethe test intervention used thesame barrier in addition to a par-ticulate graft material. Meta-analysis of the selected studiesdid not reveal any difference inCAL gain between test and con-trol groups (P = 0.774). Hetero-geneity was significant (P


274



Intervention


Chung et al.165 1990 RCT, split-mouth Bov coll OFDBenqué166 1997 CHT Bov coll + HA (rapidly Bov coll + HA

progressive (adult periodontitis)periodontitis)

Eickholz et al.167 1998 RCT, split-mouth PLA 910 ePTFENygaard-Østby et al.168 CHT ePTFE OFD

1996

Parashis et al.169 1998 CHT PLA DFDBARatka-Krüger et al.170 CHT PLA OFD

2000

* Sorted by study ranking.Abbreviations: AP = adult periodontitis; Bov coll = bovine collagen; BPBM = bovine porous bone mineral; Ca =calcium; CPF = coronally positioned flaps; DFDBA = demineralized freeze-dried bone allograft; EMD = enamelmatrix proteins; ePTFE = expanded polytetrafluoroethylene; HA = hydroxyapatite; NFGT = newly-formedgranulation tissue; OFD = open flap debridement; PLA = polylactic acid; PLA/PGA = polylactic/polyglycolicacid; PLA 910 = polyglactin 910; Por coll = porcine collagen; RPP = rapidly progressive periodontitis; TET =tetracycline; TR = titanium-reinforced.

Table 5.

Furcation-Defect Studies that Provided Standard Deviation or Error Values*

FurcationIntervention

Reference Design Class Test Control

Bouchard et al.171 1997 RCT, parallel II PLA/PGA ePTFE

Lekovic et al.172 1989 RCT, split-mouth II ePTFE OFDMetzler et al.173 1991 RCT, split-mouth II ePTFE OFD

Vest et al.174 1999 RCT II PLA + DFDBA + antibiotic regimen PLA + DFDBAWang et al.175 1994 RCT, split-mouth II Bov coll OFD

Anderegg et al.176 1991 RCT, split-mouth II ePTFE + DFDBA ePTFEBlumenthal177 1993 RCT II Bov coll ePTFE

dos Anjos et al.178 1998 RCT, split-mouth II Cellulose ePTFEFlanary et al.179 1991 RCT, split-mouth II Por coll OFD

Lekovic et al.180 1991 RCT, split-mouth II Periosteal graft as GTR OFDMachtei et al.181 1993 RCT, split-mouth II ePTFE + TET root condition ePTFE

Avera et al.182 1998 RCT, split-mouth II Periosteal membrane as GTR CRFAvera et al.182 1998 RCT, split-mouth II ePTFE OFD

Black et al.183 1994 RCT, split-mouth II Bov coll ePTFEBouchard et al.184 1993 RCT, split-mouth II ePTFE + citric acid CTG + citric acid

Caffesse et al.4 1990 RCT II ePTFE OFDDe Leonardis et al.185 1999 RCT, split-mouth II PLA + DFDBA PLA

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<0.03). One study demon-strated a statistically significantnegative effect of the use ofDFDBA in addition to PLA (P =0.007).143 Six studies exam-ined PD reduction and meta-analysis of these studies alsodid not reveal any differencesbetween test and control inter-ventions (P = 0.468) (Fig. 9,page 283).135,136,143,152,153,161

Subgroup analysis of the typesof barriers used also failed toshow any differences.

Hard tissue changes. Themeta-analysis comparing bar-rier alone to OFD using re-entryassessment was based upon5 study arms from 4 studiesand 3 barrier types (Table 9,page 284).147,159,165,168 Onlyone of these studies favoredOFD.168 None of the studiesdemonstrated a loss or lack ofbone volume gain in the GTR


275



Study Duration Augmentation



12 10 10 CAL, re-entry 2B-3B6 HA 14 43 CAL, PD, REC 3B

24 10 10 CAL, PD, REC, x-rays 3B6 15 13 CAL, PD, REC, re-entry 3B

12 12 CAL, PD, REC, x-rays 3B12 23 21 CAL, PD, REC 3B


Furcation-Defect Studies* that Provided Standard Deviation or Error Values

Study Augmentation N sites

Study Duration (months) Material Test Control Outcomes Ranking

12 15 15 VPAL, VPD, HPD, REC 1B

6 12 12 VPAL, VPD, VOPA, HOPA, REC 1B6 17 17 VPAL, VPD, VOPA, HOPA, REC 1B

9 DFDBA 12 12 VPAL, VPD, HPD, VOPA, HOPA, REC 1B12 12 12 VPAL, VPD, VOPA, HOPA, REC 1B

6 DFDBA 15 15 VPAL, VPD, VOPA, HOPA, REC 1B-2B12 VPAL, VPD, VOPA, HOPA, REC 1B-2B

6 15 15 VPAL, VPD, VOPA, HOPA, REC 1B-2B6 19 19 VPAL, VPD, VOPA, HOPA, REC 1B-2B

6 15 15 VPAL, VPD, VOPA, HOPA, REC 1B-2B12 18 18 VPAL, HPAL, VPD 1B-2B

6 14 14 VPAL, VPD, VOPA, HOPA, REC 2B9 8 8 VPAL, VPD, VOPA, HOPA, REC 2B

6 13 13 VPAL, VPD, HPD, REC 2B12 12 12 VPAL, VPD, HPD, VOPA, HOPA 2B

12 9 4 VPAL, VPD 2B12 DFDBA 12 12 VPAL, VPD, HPD, REC 2B(continued)

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276

group, while one study revealed a lack of bone volumegain in the OFD control group.165 There is a lack ofstandardization among studies examining the changein bone levels using a radiological assessment. Therewas only one study included in this systematic reviewthat demonstrated a difference in gain of bone heightof 0.90 mm, favoring GTR over OFD.157

Furcation StudiesBarrier versus open flap debridement therapy. Con-sidering all barrier types, meta-analysis of includedstudies demonstrated that GTR procedures resulted ina greater gain in vertical probing attachment (VPAL)when compared to OFD controls (Fig. 10, page 285;Tables 11, page 285; and 15, page 289) at a signifi-cance level of P <0.0001. Heterogeneity was significant(P <0.001). However, when the 2 most efficacious stud-ies were removed,182,189 the heterogeneity wasremoved and the treatment effect remained significant.Eleven studies using ePTFE barriers demonstrated adifference between test and control interventions ofweighted mean gains in VPAL of 1.39 ± 0.36 mm (P<0.0001). The single study evaluating a polymeric bar-rier115 demonstrated a gain in VPAL of 2.50 ± 0.85mm. Collagen barriers demonstrated a marginal gainof 0.10 ± 0.60 mm.

Sensitivity analysis on the effect of furcation loca-tion (maxillary versus mandibular; proximal versusfacial or lingual) failed to show a difference between

groupings. However, 2 studies that contributed 4 armsof data,120,121 contained data subsets regarding theeffect of furcation location. These studies included adiagnosis of the horizontal component of the furcationnot preoperatively, but rather after surgical debride-ment. Therefore, inclusion of these studies must bereviewed with caution. When these same studies andothers with modified standard deviation values wereexcluded from the analysis, a similar efficacy was dis-played comparing GTR to OFD.

A meta-analysis examining the outcome variable ofvertical probing depth reduction (VPD) demonstratedthat GTR results in greater VPD reduction as comparedto OFD at a significance level of P <0.0001. The hetero-geneity was significant <0.05 for the ePTFE and com-bined groupings. For the ePTFE group, when the mostefficacious study was removed from analysis,182 theheterogeneity was nonsignificant, while the effectremain significant. However, for the combined group-ing, heterogeneity remained due to the strongly posi-tive influence of polymeric barrier study115 (Fig. 11,page 286; Tables 12, page 286; and 15, page 289).Studies evaluating the gain in VOPA with barriers ascompared with OFD are summarized in Table 13 (page287). Collagen barrier usage usually resulted in greatergains in VOPA. However, statistical analysis was notperformed to confirm this trend.

A meta-analysis comparing GTR to OFD for the re-entry outcome variable horizontal open probing attach-



FurcationIntervention

Reference Design Class Test Control

Lekovic et al.186 1990 RCT II ePTFE + porous HA ePTFELuepke et al.187 1997 RCT, split-mouth II PLA + DFDBA PLA

Parashis & Mitsis188 1993 RCT, split-mouth II ePTFE + TET ePTFEPontoriero et al.189 1988 RCT, split-mouth II ePTFE OFD

Scott et al.190 1997 RCT, split-mouth II DLB + DFDBA ePTFE + DFDBASimonpietri-C et al.191 2000 RCT, split-mouth II Cellulose + anorganic bovine bone Cellulose

Andersson et al.192 1994 RCT, split-mouth II ePTFE CPFEickholz et al.167 1998 RCT, split-mouth III PLA 910 ePTFE

Eickholz et al.167 1998 RCT, split-mouth II PLA 910 ePTFEGarrett et al.193 1994 CHT III ePTFE + DFDBA DFDBA + CPF

Yamaoka et al.194 1996 RCT, split-mouth II Demineralized ilium cortical strip ePTFE

* Sorted by study ranking.Abbreviations: Bov coll = bovine collagen; CTG = connective tissue graft; CPF = coronally positioned graft; DLB = demineralized laminar bone; ePTFE =expanded polytetrafluoroethylene; HA = hydroxyapatite; OFD = open flap debridement; PLA = polylactic acid; PLA 910 = polyglactin 910; Por coll = porcinecollagen; TET = tetracycline.

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277

ment level gain (HOPA) was examined and found to besignificant in favor of GTR when all barrier types wereconsidered collectively (P <0.01) (Fig. 12, page 287;Tables 14, page 288; and 15, page 289). However, the

heterogeneity was highly significant (P <0.0001) for thecombined, ePTFE, and other groupings. The strength ofthis heterogeneity suggests that these studies shouldnot be combined for meta-analysis. The amount of post-



Study Augmentation N sites

Study Duration (months) Material Test Control Outcomes Ranking

6 Porous HA 15 15 VPAL, VPD, VOPA, HOPA, REC 2B6 DFDBA 15 15 VPAL, VPD, HPD, VOPA, HOPA, REC 2B

6 9 9 VPAL, HPAL, VPD 2B6 VPAL, HOPA 2B

6 DFDBA 12 12 VPAL, VOPA, HOPA, REC 2B6 Anorganic 15 15 VPAL, VPD, VOPA, HOPA, REC 2B

bovine bone

12 9 9 VPAL, REC 2B-3B24 5 5 VPAL, VPD 3B

24 9 9 VPAL, VPD 3B12 DFDBA 14 12 VPAL, VOPA 3B

12 15 15 VPAL, VPD, HPD, VOPA, HOPA, REC 3B

Figure 2.Meta-analysis of intrabony-defect studies examining open flap debridement versus GTR with barrier, using CAL gain as an outcome variable.Abbreviations: Bov coll = bovine collagen; ePTFE = expanded polytetrafluoroethylene; Hum coll = human collagen; PLA = polylactic acid; PLA/PGA =polylactic/ polyglycolic acid;TR = titanium-reinforced.

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treatment recession induced by the use of the physicalbarrier was also not significant when compared to OFDcontrols (Fig. 13, page 289).

ePTFE versus bioabsorbable barriers. Examiningthe outcome variables of VPAL and VPD, 8 study armsfrom 7 studies directly compared the use of ePTFE toa bioabsorbable barrier in the treatment of furcationdefects.116,117,167,171,177,178,183 When examining the

combined and polymeric barrier groupings, a statisticaldifference in favor of bioabsorbable barrier types overePTFE barriers could be detected (Figs. 14, page 289;and 15, page 290; Table 17, page 290) for VPAL out-come measures (P = 0.004 and P = 0.018, respec-tively), but not for VPD (P = 0.152). Only 2 stud-ies177,178 compared ePTFE versus bioabsorbablebarrier types while examining the re-entry outcome

278

Table 6.

Intrabony-Defect Studies* that Provided Standard Deviation or Error Values and that UsedCAL as an Outcome Variable when Comparing Membrane Only to OFD

Test Control

N Sites Outcome Outcome Outcome Outcome Difference Difference Reference Treated Intervention (mm) SD (mm) Intervention (mm) SD (mm) (mm) SD (mm)

CollagenChung et al.165 10 Bov coll 0.56 0.56 OFD −0.71 0.90 1.27 0.73

1990Blumenthal & 15 Bov coll 1.17 0.38 OFD 0.75 0.76 0.42 0.40

Steinberg148 1990

ePTFECortellini et al.133 12 ePTFE 5.20 1.40 OFD 2.30 0.80 2.90 1.10

1996Kim et al.138 19 ePTFE 4.00 2.10 OFD 2.00 1.70 2.00 1.90

1996Tonetti et al.142 15 ePTFE 4.10 1.90 OFD 2.50 0.80 1.60 1.35

1996Zybutz et al.147 2000 14 ePTFE 2.40 0.80 OFD 1.80 2.20 0.60 1.50Kiliç et al.157 1997 10 ePTFE 3.72 1.96 OFD 2.10 2.02 1.62 1.99Nygaard-Østby 15 ePTFE 2.40 2.00 OFD 2.20 1.20 0.20 1.60

et al.168 1996Cortellini et al.132 15 ePTFE-TR 5.30 2.20 OFD 2.50 0.80 2.80 1.50

1995Tonetti et al.142 1996 15 ePTFE-TR 5.30 2.20 OFD 2.50 0.80 2.80 1.50

PolymersRatka-Kruger et al.170 23 PLA 3.13 2.34 OFD 3.33 2.70 −0.20 2.52

2000Cortellini et al.131 23 PLA 3.00 1.70 OFD 1.60 1.80 1.40 1.75

1998Zybutz et al.147 2000 15 PLA 2.40 1.90 OFD 1.30 1.90 1.10 1.90Mayfield et al.159 10 PLA 1.50 1.90 OFD 1.30 1.70 0.20 1.80


2001Cortellini et al.133 12 PLA/PGA 4.60 1.20 OFD 2.30 0.80 2.30 1.00

1996Sculean et al.140 2001 14 PLA/PGA 3.10 1.50 OFD 1.70 1.10 1.40 1.30Bratthall et al.114 11 PLA/PGA 2.00 0.20 OFD 1.90 0.20 0.10 0.20

1998Joly et al.137 2002 10 PLA/PGA 2.37 0.37 OFD 1.65 0.35 0.72 0.36Tonetti et al.141 1998 69 PLA/PGA 3.04 1.64 OFD 2.18 1.46 0.86 1.55

* Sorted by test intervention.Abbreviations: Bov coll = bovine collagen; ePTFE = expanded polytetrafluoroethylene; OFD = open flap debridement; PLA = polylactic acid; PLA/PGA =polylactic/polyglycolic acid; TR = titanium-reinforced.

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variable HOPA. Insufficient data were available for com-parisons regarding this outcome variable.

Barrier versus barrier plus augmentation material.Using the outcome variable of VPAL, 6 studies exam-ined the effect of the addition of an augmenta-tion material under the physical barrier (Fig. 16, page291 and Table 16, page 290).126,176,185-187,191 Collec-tively reviewing all barriers, VPAL was significantlyenhanced by the addition of a particulate bone graft (P= 0.039). The heterogeneity was not significant. As asubgroup, ePTFE plus a particulate graft resulted in asignificantly greater gain in VPAL as compared toePTFE alone (P <0.05). Polymeric or cellulose barriertreatments were not enhanced by the use of a graft.VPD reduction was also enhanced by the addition of aparticulate graft (P = 0.004) when all barriers were col-lectively reviewed (Fig. 17, page 291). Heterogeneitywas not significant. Again, the ePTFE grouping demon-strated a significant advantage (P <0.05).

Meta-analysis of the re-entry outcome variableHOPA demonstrated an advantage to the use ofaugmentation material in addition to the GTR barrier(Fig. 18, page 291) (P <0.05), but the highly signifi-cant heterogeneity (P <0.0001) suggests that thesestudies should not be combined for meta-analysis.

Possible Prognostic FactorsFlap closure technique ranking. Most reviewed studiesutilized a “standard” flap closure technique. Regressionanalysis examined the differences among groups sortedby flap closure ranking. Examining intrabony defectsand considering all barrier types, no significant differ-

ences between the rankings could be detected. However,when considering only ePTFE barriers in intrabony-defect studies, the mean gain in CAL utilizing a spe-cialized flap closure technique (Grade 3) was 3.76 mmas compared to 2.90 mm and 2.84 mm for Grades 2and 1, respectively. But these differences were not sta-tistically different (Fig. 19, page 292).

Flap closure technique Grade 3 was not used forany of the furcation-defect studies examined. Withthe exception of horizontal probing depth reduction(HPD), regression analysis of furcation studies failed todetect a difference in any outcome variable. HPD reduc-tion was enhanced when a passively adapted, coronallyrepositioned flap technique (Grade 2) was employed(Fig. 20, page 293). HPD for Grade 1 was 1.38 ± 0.14(SE) mm and 2.71 ± 0.22 (SE) mm for Grade 2. Thisdifference was not translated to other clinical outcomemeasures with statistical significance.

Frequency of postoperative recall care frequency.Studies that utilized a more frequent recall interval,especially in the time period after 3 months, showed atendency for greater gains in attachment levels (CAL,VPAL, HPAL, HOPA). However, regression analysis uti-lizing the recall care ranking failed to detect a statisti-cal difference between these groups for all outcomevariables with the exception of PD reduction in intra-bony-defect studies (Fig. 21, page 293). PD reductionwas enhanced with a Grade 3 recall ranking, resultingin a PD reduction of 4.97 mm, as compared to 3.73mm for Grade 2 and 3.52 mm for Grade 1 (P = 0.004).

Timing of barrier removal. Accurate documentationof the time of barrier removal for non-absorbable bar-

279

Figure 3.Meta-analysis of intrabony-defect studies examining open flap debridement versus GTR with barrier, using PD reduction as an outcome variable.Abbreviations: Bov coll = bovine collagen; ePTFE = expanded polytetrafluoroethylene; Hum coll = human collagen; PLA = polylactic acid; PLA/PGA =polylactic/polyglycolic acid;TR = titanium-reinforced.

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riers was difficult as most studies described a range oftimes. The most commonly used time range was 4 to6 weeks. Therefore, differences in the effect of barrierremoval at the 4- and 6-week time intervals could notbe discerned from this dataset. Only 2 studies allowedthe barriers to remain for 8 weeks.172,188 These fur-cation defect studies reported an enhancement in VPAL

gain as compared with other furcation studies, butwithout any statistical significance.

Smoking. Eighteen studies provided some des-cription of the number of smokers in the test andcontrol populations. Comparisons between smokerand non-smoker groups were not possible as no stud-ies insured an even distribution of these populations

280

Table 7.

Intrabony-Defect Studies* that Provided Standard Deviation or Error Values and that UsedPD as an Outcome Variable when Comparing Membrane only to OFD

Test Control


ePTFECortellini et al.133 12 ePTFE 5.90 1.00 OFD 4.30 1.40 1.60 1.20

1996Kim et al.138 19 ePTFE 4.80 1.80 OFD 3.30 1.60 1.50 1.70

1996Tonetti et al.142 15 ePTFE 5.50 2.60 OFD 4.60 1.20 0.90 1.90

1996Zybutz et al.147 14 ePTFE 3.10 1.20 OFD 2.50 1.90 0.60 1.55

2000Kiliç et al.157 10 ePTFE 5.83 2.84 OFD 3.17 0.98 2.66 1.91

1997Nygaard-Østby 15 ePTFE 3.80 1.20 OFD 2.90 1.10 0.90 1.15

et al.168 1996Cortellini 15 ePTFE-TR 6.30 1.40 OFD 4.60 1.30 1.70 1.35

et al.132 1995Tonetti et al.142 15 ePTFE-TR 6.30 2.50 OFD 4.60 1.20 1.70 1.85

1996

PolymersRatka-Kruger 23 PLA 3.71 1.92 OFD 3.66 2.67 0.05 2.30

et al.170 2000Cortellini et al.131 23 PLA 4.30 2.30 OFD 3.00 1.50 1.30 1.90

1998Zybutz et al.147 15 PLA 3.30 2.10 OFD 2.20 1.70 1.10 1.90

2000Mayfield et al.159 10 PLA 2.90 1.80 OFD 2.50 1.90 0.40 1.85


2001Tonetti et al.141 69 PLA/PGA 4.03 1.81 OFD 3.09 1.67 0.94 1.74


1996Sculean et al.140 14 PLA/PGA 4.20 1.90 OFD 3.70 1.40 0.50 1.65

2001Bratthall et al.114 11 PLA/PGA 3.60 0.20 OFD 2.90 0.20 0.70 0.20

1998Joly et al.137 10 PLA/PGA 2.64 0.42 OFD 1.84 0.36 0.80 0.39

2002

* Sorted by test intervention.Abbreviations: ePTFE = expanded polytetrafluoroethylene; OFD = open flap debridement; PLA = polylactic acid; PLA/PGA = polylactic/polyglycolic acid; TR =titanium-reinforced.

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among the test and control interventions. Of thesestudies, most found a negative association betweensmoking and clinical outcomes. The statistical sig-nificance is unknown. Only 5 studies excludedsmoker patients.

Other outcomes. Patient-centered outcomes, suchas surgical complications and esthetically unacceptableresults, were not consistently reported. Only 13 studies

made mention of the incidence of postoperative abscessformation or some description of patient discomfort. Ofthe 13 studies examining the incidence of abscess for-mation, only 4 studies described any occurrence ratefor control groups. Likewise, only 4 described occur-rences for the test groups during the healing period.When reported, the incidence of abscess formation was15% or less.

281

Table 8.

Intrabony-Defect Studies* that Provided Standard Deviation or Error Values and that UseREC as an Outcome Variable When Comparing Membrane Only to OFD

Test Control


CollagenCamargo et al.149 22 Bov coll + 1.11 1.40 OFD 1.36 1.40 −0.25 1.40

2000 BPBM

ePTFECortellini et al.133 12 ePTFE 1.20 1.30 OFD 2.00 1.60 −0.80 1.45

1996Kim et al.138 19 ePTFE 0.90 1.20 OFD 1.20 1.40 −0.30 1.30

1996Zybutz et al.147 14 ePTFE 0.80 0.90 OFD 0.00 1.30 0.80 1.10

2000Kiliç et al.157 10 ePTFE 2.12 0.86 OFD 1.05 0.55 1.07 0.71

1997Nygaard-Østby 15 ePTFE 1.70 1.50 OFD 0.70 0.90 1.00 1.20

et al.168 1996Cortellini et al.132 15 ePTFE-TR 0.90 1.60 OFD 2.10 1.60 −1.20 1.60

1995

PolymersRatka-Kruger 23 PLA 0.71 1.25 OFD 0.33 1.07 0.38 1.16

et al.170 2000Zybutz et al.147 15 PLA 0.70 0.90 OFD 0.00 1.10 0.70 1.00




1996Sculean et al.140 14 PLA/PGA 1.10 1.40 OFD 1.70 1.10 −0.60 1.25

2001Bratthall et al.114 11 PLA/PGA 2.30 0.20 OFD 1.60 0.20 0.70 0.20

1998Tonetti et al.141 69 PLA/PGA 1.00 1.40 OFD 1.01 1.18 −0.01 1.29

1998Joly et al.137 10 PLA/PGA 1.60 0.21 OFD 0.67 0.09 0.93 0.15

2002

* Sorted by test intervention.Abbreviations: Bov coll = bovine collagen; BPBM = bovine porous bone mineral; ePTFE = expanded polytetrafluoroethylene; OFD = open flap debridement;PLA = polylactic acid; PLA/PGA = polylactic/polyglycolic acid; TR = titanium-reinforced.

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Long-term patient-centered outcomes, such as toothloss and ease of maintenance, were not reported in thestudies selected for inclusion in the current systematicreview.

DISCUSSIONThe purpose of this systematic review (SR) was toanswer the focused question, “In patients with peri-odontal osseous defects, what is the effect of physical

282

Figure 4.Meta-analysis of intrabony-defect studies examining open flap debridement versus GTR with barrier, using increase in gingival REC as an outcomevariable.Abbreviations: ePTFE = expanded polytetrafluoroethylene; PLA = polylactic acid.

Figure 5.Meta-analysis of intrabony-defect studies that compare ePTFE barrier to a bioabsorbable barrier, using CAL gain as an outcome variable.Abbreviations: ePTFE = expanded polytetrafluoroethylene; PLA = polylactic acid; PLA 910 = polyglactin 910.

Figure 6.Meta-analysis of intrabony-defect studies that compare ePTFE barrier to a bioabsorbable barrier, using PD reduction as an outcome variable.Abbreviations: ePTFE = expanded polytetrafluoroethylene; PLA = polylactic acid; PLA 910 = polyglactin 910.

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barriers compared with surgical controls on clinical,radiographic, adverse and patient-centered outcomes?”This systematic review also aimed to expand upon 2previously systematic reviews of GTR as a regenerativetherapy.196,197 These reviews limited their scope toRCTs of intrabony defects or furcation defects, respect-ively. Our review aimed to examine GTR studies withthese defect types separately and collectively, in an

attempt to better understand some of the heterogene-ity described in these earlier systematic reviews.

The current SR also differed in that the reviewedstudies were not limited to RCTs. Despite this lack oflimitation, only a few additional cohort studies satis-fied the inclusion criteria. Our SR also included stud-ies of 6 months or greater. Needleman et al.196 did notinclude studies of less than one year duration. When

283

Figure 7.Meta-analysis of intrabony-defect studies that compare an expanded polytetrafluoroethlylene (ePTFE) barrier to a bioabsorbable barrier, using RECincrease as an outcome variable.

Figure 8.Meta-analysis of intrabony-defect studies directly comparing the use of a barrier alone with the use of a barrier plus augmentation, using CAL gain asan outcome variable.Abbreviations: BOV coll = bovine collagen; BPBM = bovine porous bone mineral; DFDBA = demineralized freeze-dried boneallograft; ePTFE = expanded polytetrafluoroethylene; HA = hydroxyapatite; PLA = polylactic acid.

Figure 9.Meta-analysis of intrabony-defect studies directly comparing the use of a barrier alone with the use of a barrier plus augmentation, using PD reductionas an outcome variable.Abbreviations: Bov coll = bovine collagen; BPBM = bovine porous bone mineral; DFDBA = demineralized freeze-dried boneallograft; ePTFE = expanded polytetrafluoroethylene; HA = hydroxyapatite; PLA = polylactic acid.

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appropriate, we also included studies that combinedaugmentation materials and barriers in the GTRprocess. While acknowledging that while clinical attach-ment levels (CAL or VPAL) are surrogate variables,but considered the most reliable clinical measure ofregeneration, this SR examined 10 primary outcomemeasures, including attachment levels in both verti-cal and horizontal directions, probing depths, recession,and re-entry measurements. While this expansion ofprimary outcome measures increased the complexityof the analysis, our meta-analysis demonstrated thatnot all outcome variables followed the trends outlinedby attachment level gains.

Incomplete data representation and description ofmethods prevented the inclusion of many studies.

Most studies failed to describethe methodology of patientselection, randomization, ther-apist and examiner maskingand allocation concealment.Most significant of these prob-lems was the failure to describestandard deviation (SD) orstandard error values (SE).Without these values, meta-analysis is not possible. Jepsenet al.197 estimated these valuesfrom split-mouth studies de-rived from the literature. Thisuse of estimated values of stan-

dard deviations from unrelated studies may or maynot be valid. Our review also included such studiesthat did not present standard deviations or standarderror values, and their possible influence on the ana-lysis was noted.

Meta-analysis of the studies examining the effect ofGTR compared to OFD procedures, using the outcomevariable CAL and VPAL, demonstrated that GTR wasstrongly favored in the treatment of both intrabony andfurcation defects (P <0.0001). This finding was morerobust than previously reported and is probably relatedto the greater number of studies included for analysisin this SR. When PD or VPD were considered, similarrobust findings favoring GTR were demonstrated.HOPA, a horizontal re-entry outcome measure, was also

284

Table 10.

Summary of the Effect of the Use of a Physical Barrier asCompared with OFD in the Treatment of Intrabony Defects*

Barrier CAL SD PD SD

Collagen 0.95 ±0.47 1.06 ±0.37

Polymer 0.92 ±0.18 0.89 ±0.14

Expanded 1.61 ±0.25 1.41 ±0.20polytetrafluoroethylene

* Differences between CAL gain and PD reduction between barrier and OFD control (mm) [mean ± standarddeviation].

Table 9.

Intrabony-Defect Studies that Provided Standard Deviation or Error Values and that UsedRe-entry as an Outcome Variable when Comparing Membrane Only to OFD*

Test Control


CollagenChung et al.165 10 Bov coll 1.16 0.94 OFD 0 0.78 1.16 0.86

1990

ePTFEZybutz et al.147 14 ePTFE 2.7 2.3 OFD 2.4 3 0.30 2.65

2000Nygaard-Østby 15 ePTFE 2 2 OFD 2.4 0.9 −0.40 1.45

et al.168 1996

PolymersZybutz et al.147 15 PLA 2.3 3 OFD 1.5 1.6 0.80 2.30


1998

* Studies expressing only a percent of defect fill were excluded.Abbreviations: Bov coll = bovine collagen; ePTFE = expanded polytetrafluoroethylene; OFD = open flap debridement; PLA = polylactic acid.

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285

Figure 10.Meta-analysis of furcation-defect studies examining open flap debridement (OFD) versus GTR with barrier, using VPAL gain as an outcome variable.ePTFE = expanded polytetrafluoroethylene; Mand = mandibula; Max = maxilla.

Table 11.

Furcation-Defect Studies* that Provided Standard Deviation or Error Values and that UsedVPAL as an Outcome Variable when Comparing Membrane Only to OFD

Test Control

N Sites Outcome Outcome Outcome Difference DifferenceReference Treated Intervention (mm) SD (mm) Intervention (mm) SD (mm) (mm) SD (mm)

CollagenFlanary et al.179 19 Por coll 1.50 1.10 OFD 0.80 1.20 0.70 1.15

1991Wang et al.175 12 Bov coll 1.67 0.76 OFD 0.67 2.14 1.00 1.45

1994Lekovic et al.180 15 Periosteal graft 2.40 1.35 OFD −0.70 1.16 3.10 1.26

1991

ePTFELekovic et al.172 12 ePTFE 2.86 1.80 OFD −0.12 2.84 2.98 2.32

1989Metzler et al.173 17 ePTFE 1.00 0.90 OFD 0.20 0.60 0.80 0.75

1991Avera et al.182 8 ePTFE 1.50 0.46 OFD 0.13 0.48 1.37 0.47

1998Caffesse et al.4 9 ePTFE 1.80 1.30 OFD 0.60 1.90 1.20 1.60

1990Pontoriero 21 ePTFE 3.50 1.50 OFD 0.90 1.00 2.60 1.25

et al.189 1988Andersson 9 ePTFE 0.70 1.03 OFD 0.40 0.82 0.30 0.93

et al.192 1994

* Sorted by test intervention.Abbreviations: Bov coll = bovine collagen; ePTFE = expanded polytetrafluoroethylene; OFD = open flap debridement; Por coll = porcine collagen.

significantly greater for GTR as compared to OFDprocedures (P = 0.001), but the heterogeneity wassignificant.

The inclusion of a greater number of studies alsofacilitated subgroup or sensitivity analysis regarding thepossible effect of the type of barrier utilized. For intra-

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bony defect studies, both ePTFE and polymeric barriersperformed with similar efficacy when compared toOFD. In intrabony studies that directly comparedePTFE to a bioabsorbable barrier, CAL was enhancedwith ePTFE, but not with statistical significance.

In the treatment of furcation defects using an OFDcontrol, there are relatively few studies which examined

the use of polymeric barriers alone. More furcation stud-ies directly compared ePTFE to a polymeric barrier.This is probably related to the fact that ePTFE becamethe perceived “gold standard” in regeneration, not OFD,due to the number of studies examining this material.When ePTFE is compared to a polymeric barrier in thetreatment of furcation defects, there was no significant

286

Figure 11.Meta-analysis of furcation-defect studies examining open flap debridement (OFD) versus GTR with barrier, using VPD reduction as an outcomevariable. ePTFE = expanded polytetrafluoroethylene; Mand = mandibula; Max = maxilla.

Table 12.

Furcation-Defect Studies* that Provided Standard Deviation or Error Values and that UsedVPD as an Outcome Variable When Comparing Membrane Only to OFD

Test Control

N Sites Outcome Outcome Outcome Difference Difference Reference Treated Intervention (mm) SD (mm) Intervention (mm) SD (mm) (mm) SD (mm)

CollagenLekovic et al.180 15 Periosteal 4.30 0.92 OFD 1.60 1.12 2.70 1.02

1991 graftLekovic et al.195 14 Periosteal 3.66 0.89 OFD 3.89 1.31 −0.23 1.10

1998 graftFlanary et al.179 19 Por coll 2.10 1.10 OFD 1.20 1.10 0.90 1.10


1994

ePTFELekovic et al.172 12 ePTFE 4.09 2.94 OFD 1.14 2.77 2.95 2.86


1991Avera et al.182 8 ePTFE 2.88 0.48 OFD 1.38 0.65 1.50 0.57

1998Caffesse et al.4 9 ePTFE 2.80 1.00 OFD 1.60 0.90 1.20 0.95

1990


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difference between observed changes in VPAL or VPDoutcome measures. Not enough studies examined HOPAin this context. In summary, both ePTFE and polymericbarriers performed in similar manner when used alonein GTR in the treatment of intrabony or furcation defects.

When augmentation of the barrier with a particu-late graft was examined, a dichotomy was seen inthe behavior of intrabony and furcation defects. Aug-mentation procedures did not enhance CAL or PDoutcomes when used in the treatment of intrabony

defects. This is in contrast to furcation defects whereinaugmentation enhanced VPAL and VPD outcomes(P <0.05 and P <0.005). HOPA were similarly influ-enced, but with heterogeneity among the studies. Sincedifficulty in maintaining the space under the barrier ismore likely to be a problem in a non-contained fur-cation defect, an augmentation material might demon-strate an advantage in furcation defects as opposed tointrabony defects.70,198 Unfortunately, this assumptioncannot be proven without descriptions of the bony con-

287

Figure 12.Forest plot of furcation-defect studies examining open flap debridement (OFD) versus GTR with barrier, using HOPA gain as an outcome variable.ePTFE = expanded polytetrafluoroethylene; Mand = mandibula; Max = maxilla.

Table 13.

Furcation-Defect Studies* that Provided Standard Deviation or Error Values and that UsedVOPA as an Outcome Variable When Comparing Membrane Only to OFD

Test Control

N Sites Outcome Outcome Outcome Outcome Difference DifferenceReference Treated Intervention (mm) SD (mm) Intervention (mm) (mm) (mm) (mm)

CollegenLekovic et al.180 15 Periosteal graft 2.00 0.54 OFD −1.27 1.33 3.27 0.94

1991Lekovic et al.195 14 Periosteal 1.93 0.56 OFD 0.20 0.97 1.73 0.77

1998 membrane as GTRFlanary et al.179 19 Por coll 1.00 1.20 OFD 0.60 1.10 0.40 1.15


1994

ePTFELekovic et al.172 12 ePTFE 0.21 1.66 OFD 0.24 1.59 −0.03 1.63


1991Avera et al.182 8 ePTFE 0.00 0.10 OFD −0.69 0.25 0.69 0.18

1998


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288

figurations of the defect. Very few studies contained anydescription of the bony defect morphology. Future stud-ies should examine what defect morphologies would bemore likely to benefit from the use of an augmentationmaterial in addition to the barrier in GTR procedures.

The effect of furcation defect location was examinedby Jepsen et al.197 in their SR on GTR for the treatmentof furcation defects. Their SR utilized GTR furcation stud-ies that our SR excluded for data presentation problems.Unfortunately, some of these studies excluded in the cur-rent SR are some of the very few that examined the role

of furcation location on the regenerative outcome inGTR.92,95 Therefore, our SR cannot provide evidenceabout this possible relationship.

The group of Cortellini, Tonetti, and PiniPrato9,32,127,129,132-134,141 and Murphy50 have exam-ined the use specialized flap techniques that facilitateprimary closure over the barrier. The implied purposeof these procedures is to enhance the regenerative out-come and decrease the frequency of complications byreducing the development of a pseudopocket in thespace lateral to the barrier. The current SR attempted

Table 14.

Furcation-Defect Studies* that Provided Standard Deviation or Error Values and that UsedHOPA as an Outcome Variable

Test Control

N Sites Outcome Outcome Outcome Outcome Difference DifferenceReference Treated Intervention (mm) SD (mm) Intervention (mm) (mm) (mm) (mm)

Augmentation material + barrier versus barrierAnderegg et al.176 15 ePTFE + 2.40 1.50 ePTFE 1.00 0.80 1.40 1.15

1991 DFDBALekovic et al.186 15 ePTFE + 1.60 0.81 ePTFE 0.13 0.34 1.47 0.58

1990 porousHA

Simonpietri-C et al.191 15 Cellulose + 3.27 1.39 Cellulose 2.47 0.99 0.80 1.192000 anorganic

bovinebone

Luepke et al.187 15 PLA + 2.10 1.12 PLA 1.80 1.26 0.30 1.191997 DFDBA

Barrier versus ePTFEBlumenthal177 12 Bov coll 2.50 0.67 ePTFE 1.83 1.03 0.67 0.85

1993dos Anjos et al.178 15 Cellulose 2.90 1.00 ePTFE 2.90 1.10 0.00 1.05

1998

Barrier versus OFDWang et al.175 12 Bov coll 2.04 1.48 OFD 1.08 2.11 0.96 1.80

1994Flanary et al.179 19 Por coll 1.50 0.80 OFD 0.80 0.80 0.70 0.80

1991Lekovic et al.180 15 Periosteal 1.60 0.63 OFD −0.20 0.56 1.80 0.60

1991 graftLekovic et al.195 14 Periosteal 1.60 0.79 OFD 0.13 3.37 1.47 2.08

1998 graft

ePTFE versus OFDAvera et al.182 8 ePTFE 1.19 0.16 OFD −0.69 0.23 1.88 0.20

1998Lekovic et al.172 12 ePTFE 0.18 1.84 OFD 0.14 1.17 0.04 1.51


1991

* Sorted by test intervention.Abbreviations: Bov coll = bovine collagen; DFDBA = demineralized freeze-dried bone allograft; ePTFE = expanded polytetrafluoroethylene; HA =hydroxyapatite; OFD = open flap debridement; PLA = polylactic acid; Por coll = porcine collagen.

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to correlate the incidence of complicationswith prognostic variables, but was unableto do so because of lack of data. There-fore, evidence-based statements cannotbe made regarding use of these proce-dures and the incidence of complications.However, retrospective studies employingthese techniques in a microsurgical envi-ronment have claimed a greater than 90%rate of flap coverage over the barrier at6 weeks.50,128 It is believed that if the bar-rier remains covered during the healingperiod, the rate of complications will bedecreased.9 This SR did provide limitedevidence that specialized flap proceduresresult in an increase in mean attachmentlevel gain for intrabony defects, but this


289

Figure 13.Meta-analysis of furcation-defect studies examining open flap debridement (OFD) versus GTR with barrier, using REC change as an outcome variable.ePTFE = expanded polytetrafluoroethylene.

Figure 14.Meta-analysis of furcation-defect studies that compare an expanded polytetrafluoroethylene (ePTFE) barrier to a bioabsorbable barrier, using VPALgain as an outcome variable Abbreviation: Mand = mandibula.

Table 15.

Difference in Weighted Means of All Furcation-DefectStudies Evaluated Comparing a Physical Barrier toOFD Controls and Using VPAL, VPD, and HOPA asOutcome Measures*

Barrier VPAL SD VPD SD HOPA SD

Collagen 0.10 ±0.60 −0.04 ±0.52 0.96 ±0.91

Other 1.76 ±0.65 1.69 ±0.57 1.18 ±0.54

Polymeres 2.50 ±0.85 2.30 ±0.74 Insufficient data

Expanded 1.39 ±0.36 1.01 ±0.31 0.99 ±0.31polytetrafluoroethylene

* In mm (mean ± standard deviation; SD).

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finding is not statistically significant. It is of interestthat this advantage was seen only when ePTFE barri-ers were used and not bioabsorbable barriers. Like-wise, passive adaptation and coronal repositioning of

290

Figure 15.Meta-analysis of furcation-defect studies that compare an expanded polytetrafluoroethylene (ePTFE) barrier to a bioabsorbable barrier, using VPDreduction as an outcome variable.

the gingival flap in furcation GTR proce-dures statistically enhanced HPD reduc-tion, but not other outcome variables. Asmore clinical trials make use of these tech-niques, a better understanding of the effectof flap management on regenerative out-comes can be gained.

Needleman et al.196 appropriately ques-tioned whether the inclusion of studies witha very frequent recall program skewedresults in favor of the regenerative proce-dure. Indeed, our SR demonstrated that aprotocol that utilized a monthly mainte-nance schedule for the duration of thestudy enhanced the PD reduction for intra-bony defects only. No other outcomeswere enhanced. Therefore, the frequencyof the recall schedule cannot fully explainsome of the heterogeneity identified in pre-vious systematic reviews.

Despite the robust findings favoringGTR over OFD, the variability in outcomesmeasures that are clinically relevant con-tinues to be a problem with GTR proce-dures. For example, data subsets onsmokers were not consistently availabledespite the fact that findings from such apopulation could significantly alter results.Well-designed studies insure that patientsand prognostic variables are evenly dis-tributed over both test and control inter-ventions.131 Unfortunately, these protocolconsiderations were not common in thestudies included for this review.

REVIEWER’S CONCLUSIONS1. In the treatment of intrabony defects, GTR proce-dures compared to OFD controls result in significantlymore favorable gains in CAL and PD reduction.

Table 16.

Difference in Weighted Means of All Furcation-DefectStudies Evaluated Comparing a Physical Barrier Controlto the Same Barrier with an Augmentation Material,Using VPAL, VPD, and HOPA as Outcome Measures

Barrier VPAL SD VPD SD HOPA SD

Other −0.20 ±0.50 0.20 ±0.22 0.80 ±0.61

Polymers 0.39 ±0.37 0.51 ±0.16 0.30 ±0.61

Expanded 1.10 ±0.31 0.66 ±0.14 1.20 ±0.38polytetrafluoroethylene


Table 17.

Difference in Weighted Means of All Furcation-DefectStudies Evaluated Comparing the Use of an ExpandedPolytetrafluoroethylene Physical Barrier Controlto Another Barrier, Using VPAL, VPD, and HOPA asOutcome Measures*

Membrane VPAL SD VPD SD HOPA SD

Collagen 0.54 ±0.10 0.37 ±0.24 Insufficientdata

Other 0.30 ±0.13 0.40 ±0.32

Polymeres 0.39 ±0.04 0.14 ±0.10


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2. In the treatment of furcation defects, GTR pro-cedures compared to OFD controls result in signifi-cantly more favorable gains in VPAL, reductions inVPD, and improvements in HOPA measurements.

3. In the treatment of intrabony defects, meta-analy-sis did not show any statistically significant superiorresults among the barrier types evaluated. However,the type of barrier utilized might account for some of

the heterogeneity of the data. In the treatment of fur-cation defects, the type of barrier employed did affectthe surrogate variable of VPAL, since VPAL wasenhanced only with the use of ePTFE and polymericbarriers.

4. The use of augmentation materials in addition tothe physical barrier enhances the regenerative out-come in the treatment of furcation defects treated with

291

Figure 16.Meta-analysis of furcation-defect studies directly comparing the use of a barrier alone with the use of a barrier plus augmentation, using VPAL gain asan outcome variable.Abbreviations: DFDBA = demineralized freeze-dried bone allograft; ePTFE = expanded polytetrafluoroethylene; HA =hydroxyapatite; Mand = mandibula.

Figure 17.Meta-analysis of furcation-defect studies directly comparing the use of a barrier alone with the use of a barrier plus augmentation, using VPD reductionas an outcome variable. Abbreviations: DFDBA = demineralized freeze-dried bone allograft; ePTFE = expanded polytetrafluoroethylene;HA = hydroxyapatite; Mand = mandibula.

Figure 18.Meta-analysis of furcation-defect studies directly comparing the use of a barrier alone with the use of a barrier plus augmentation, using HOPAreduction as an outcome variable. Abbreviations: DFDBA = demineralized freeze-dried bone allograft; ePTFE = expanded polytetrafluoroethylene;HA = hydroxyapatite; Mand = mandibula.

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GTR. There is no advantage to the use of augmenta-tion materials in addition to the use of the physicalbarrier in the treatment of intrabony defects.

5. The use of specialized flap techniques mayenhance clinical outcomes, but there are insufficientdata at this time to demonstrate superiority with the useof these techniques.

6. A monthly frequency maintenance scheduleresults in probing depth reduction, but the use of thisregimen does not statistically improve clinical attach-ment level outcomes in GTR.

7. There are insufficient data available to performmeta-analysis regarding the enhancement of toothsurvival, ease of post-treatment maintenance, enhance-ment of esthetic outcomes, or furcation closure facil-itated by GTR procedures.

ACKNOWLEDGMENTThe authors acknowledge the efforts of Dr. Mark A.Reynolds in screening the articles.

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Figure 20.Regression analysis of furcation-defect studies examining the relationship between flap closure technique ranking and the reduction in horizontalprobing depth reduction HPD (mm). Group1 and 2 are statistically different from one another.

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189. Pontoriero R, Lindhe J, Nyman S, Karring T, RosenbergE, Sanavi F. Guided tissue regeneration in degree IIfurcation-involved mandibular molars. A clinical study.J Clin Periodontol 1988;15:247-254.

190. Scott TA, Towle HJ, Assad DA, Nicoll BK. Comparisonof bioabsorbable laminar bone membrane and non-bioabsorbable ePTFE membrane in mandibular furca-tions. J Periodontol 1997;68:679-686.

191. Simonpietri-C JJ, Novaes AB Jr, Batista EL Jr, Filho EJF.Guided tissue regeneration associated with bovine-derivedanorganic bone in mandibular class II furcation defects. 6-month results at re-entry. J Periodontol 2000;71:904-911.

192. Andersson B, Bratthall G, Kullendorff B, Gröndahl K,Rohlin M, Attström R. Treatment of furcation defects.Guided tissue regeneration versus coronally positionedflap in mandibular molars; a pilot study. J Clin Peri-odontol 1994;21:211-216.

193. Garrett S, Gantes B, Zimmerman G, Egelberg J. Treat-ment of mandibular class III periodontal furcation defects.Coronally positioned flaps with and without expandedpolytetrafluoroethylene membranes. J Periodontol 1994;

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65:592-597.194. Yamaoka SB, Mellonig JT, Meffert RM, Arnold RM,

Nummikoski PV, Mealey BL. Clinical evaluation of dem-ineralized-unicortical-ilium-strips for guided tissueregeneration. J Periodontol 1996;67:803-815.

195. Lekovic V, Klokkevold PR, Camargo PM, Kenney EB,Nedic M, Weinlaender M. Evaluation of periosteal mem-branes and coronally positioned flaps in the treatmentof class II furcation defects: A comparative clinicalstudy in humans. J Periodontol 1998;69:1050-1055.

196. Needleman IG, Giedrys-Leeper E, Tucker RJ, WorthingtonHV. Guided tissue regeneration for periodontal infra-bonydefects. Cochrane Database Syst Rev 2001;(2):CD001724.

197. Jepsen S, Eberhard J, Herrera D, Needleman I. A sys-tematic review of guided tissue regeneration for peri-odontal furcation defects. What is the effect of guidedtissue regeneration compared with surgical debride-ment in the treatment of furcation defects? J Clin Peri-odontol 2002;29(Suppl. 3):103-116.

198. Schallhorn RG, McClain PK. Periodontal regenerationusing combined techniques. Periodontol 2000 1993;1:109-117.

Correspondence: Dr. Kevin G. Murphy, Suite 2, 4 W. Uni-versity Pkwy., Baltimore, MD 21218. E-mail: [email protected].

Accepted for publication October 5, 2003.

APPENDIX ACONSENSUS REPORT

Members of the Section read and studied the reviewtitled “Guided Tissue Regeneration for the Treatment ofPeriodontal Intrabony and Furcation Defects. A Sys-tematic Review” by Kevin G. Murphy and John C. Gun-solley. The focused PICO question addressed by this evi-dence-based systematic review is: “In patients withperiodontal osseous defects, what is the effect of phys-ical barriers compared with surgical controls on clinical,radiographic, adverse and patient-centered outcomes?”

INTRODUCTIONA survey of Section members established that therewere no conflicts of interest that would have an impactupon their deliberations or decisions. This Sectionfocused on evaluation of the evidence presented in thesystematic review and on challenging the evidence withthe personal knowledge and clinical experience of allthe members. The discussion focused on addressingthe PICO question and data provided by the currentsystematic review and prior systematic reviews.

The PICO question limited the scope of the system-atic review. The systematic review protocol includedonly high quality randomized controlled clinical trials(RCTs). A wide body of information that may haveexplored other aspects of this field was not included.Clinical experience and knowledge of the group iden-tified several areas that could not be captured by the

conclusions of the report and which might have animpact upon the clinical utilization of the informationdeveloped as a result of this workshop.

Clinical considerations such as tooth morphology,gingival characteristics, tooth mobility, strategic valueof the tooth, furcation defect location (maxillary ormandibular), furcation severity, the individuality of thedefect, intrabony defect type (number of walls), useof adjunctive anti-infective therapies, and patientoral hygiene status may affect clinical outcomes andtherefore treatment selection. These and other factors,in addition to the recommendations made below inresponse to question 5, may account for variability inthe response to therapy and require specific decisionmaking by clinicians on a case-by-case basis. Conse-quently one could anticipate a more favorable outcomethan reported in this meta-analysis when treatment isindividualized to a specific clinical condition.

1. Does the Section agree that the evidence-basedsystematic review is complete and accurate?The data review was complete and accurate within thecontext of the question posed. Because of the scopeof the subject and the breadth of the data available,the analysis and interpretation of the data collectedmay be expanded to include: furcation closure, mor-bidity, and long-term outcomes.

Furcation fill/closure. The optimum clinical resultfrom the application of GTR to furcation defects is com-plete furcation fill/closure. Data reported in the sys-tematic review that did not meet the stipulated criteriafor quantitative analyses, because of the lack of a con-sistently applied criterion for furcation fill/closure, indi-cated that complete closure was an infrequent event.

Morbidity. Adverse events and patient concerns areimportant considerations in assessing the risk/benefitratio of a procedure. Observational evidence seems toindicate that GTR with non-resorbable membranes isassociated with increased morbidity. Evidence withbioabsorbable membranes detected no differencebetween GTR and access flap control.

Long-Term Effects. Obtaining and maintainingimproved attachment levels and extending tooth sur-vival with GTR over extended periods of time areimportant. Data available for intrabony and furcationdefects1-6 but not included in the meta-analysis anddata that became available after the cut-off date7 indi-cate that clinical attachment levels and teeth can bemaintained for periods of 5 years or more with propermaintenance care.

2. Has any new information been generatedor discovered since the evidence-based searchcut-off date?New information has been generated since the January2002 search cut-off date, but the results have not alteredthe general conclusions of the review.

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3. Does the Section agree with the interpretationsand conclusions of the reviewers?After assessment of the original evidence, the Sectionagrees with the following conclusions:

1. In the treatment of intrabony and furcationdefects, GTR is significantly more favorable when com-pared to open flap debridement procedures when theintrabony surrogate outcome variables of clinicalattachment level (CAL) and probing depth (PD), andthe furcation surrogate outcome variables (i.e., verti-cal attachment level [VPAL], vertical probing depth[VPD], horizontal probing attachment [HOPA]) areevaluated.

2. In the treatment of intrabony defects, the meta-analysis did not show any statistically significant supe-rior results among the barriers evaluated. However, thetype of barrier utilized can describe some of theheterogeneity of the data. In the treatment of furcationdefects, the type of barrier employed did affect thesurrogate variable VPAL, as VPAL was enhanced onlywith the use of ePTFE and polymeric barriers.

3. The use of augmentation materials in addition tothe physical barrier enhances the regenerative out-come in the treatment of furcation defects treated withGTR. There is no advantage to the use of augmenta-tion materials in addition to the use of the physicalbarrier in the treatment of intrabony defects.

4. The use of specialized flap techniques mayenhance clinical outcomes, but there is not sufficientdata at this time to demonstrate superiority with the useof these techniques.

5. A monthly frequency maintenance scheduleresults in probing depth reduction, but the use of thisregimen does not statistically improve clinical attach-ment level outcomes in GTR.

6. There are insufficient data available to performa meta-analysis regarding the enhancement of toothsurvival, ease of post-treatment maintenance, enhance-ment of esthetic outcomes, or furcation closure facil-itated by GTR procedures.

4. What further research needs to be done relative tothe focused questions of the evidence-based review?The members of the Section observed that the major-ity of published research is focused on surrogate clini-cal measures. Such research was critical in providing theevidence of efficacy. Relatively few studies so far havefocused on patient-centered outcomes. Data are neededwith relation to the benefit of periodontal regenerationin terms of tooth survival, improved function, esthetics,ease of maintenance, and patient comfort. The Sectionalso felt that there was an urgent need to identify the pos-sible sources of variability of results, such as patient- anddisease-based factors and defect morphology. Moreinformation is also needed to assist in selection of theappropriate treatment options for specific clinical situ-

ations. Research is needed to evaluate new technologies(e.g., tissue engineering, growth factors) used to mod-ify or in conjunction with physical barriers on clinical,histologic, and patient-centered outcomes.

5. How can the information from the evidence-based review be applied to patient management?A. Barrier membranes provide additional benefits overopen flap debridement in terms of improving clinicalattachment levels and reducing probing depths in intra-bony and furcation defects.

Level of Evidence:8 Strong.Rationale: Meta-analyses from this systematic

review utilizing over 50 Level I RCTs and 2 other sys-tematic reviews.

B. In intrabony defects the morbidity associated withthe use of bioabsorbable membranes is no greater thanthat with open flap debridement.

Level of Evidence: Strong.Rationale: Data from 1 large multi-center level I

RCT specifically designed to examine patient morbid-ity.

C. The use of bone replacement grafts in additionto the physical barrier enhances clinical outcomes infurcation defects.

Level of Evidence: Strong.Rationale: Meta-analyses from this systematic

review utilizing 6 level I RCTs.D. The use of a barrier alone provides similar results

to the combination of bone replacement graft plus bar-rier in intrabony defects.


review utilizing 6 level I RCTs. However, the Sectionfeels strongly that the randomized trials did not cap-ture the individuality of the anatomy of the defectsand, therefore, the combination may be appropriatein specific clinical situations.

E. Applications of barriers in intrabony defects maybe associated with increased recession of the gingivalmargin compared to open flap debridement.


review of 19 level I RCTs.F. There was no difference in gingival recession fol-

lowing the application of bioresorbable or non-resorbable barriers in intrabony defects.


review of 6 level I RCTs. However, the Section felt thatgingival recession as a postoperative complication maylead to adverse clinical outcomes.

G. Coronally advanced flaps to cover the barrier areassociated with better clinical outcomes in furcationdefects.

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review of 4 level I RCTs.H. In GTR procedures for treating intrabony defects

papilla preservation flaps are probably associated withbetter clinical outcomes.

Level of Evidence: Moderate.Rationale: This systematic review of 6 RCTs and

additional level II studies.I. Intensive postoperative care protocols result in

shallower probing depths in the treatment of intrabonydefects.


review of 6 level I RCTs.J. There is incomplete evidence to indicate that

intensive postoperative care protocols after GTR pro-cedures enhance clinical outcomes other than reduc-tion in probing depths.

Level of Evidence: Incomplete.Rationale: Inadequate data on this topic from 6 level I

RCTs.

REFERENCES1. Gottlow J, Nyman J, Karring T. Maintenance of new

attachment gained through guided tissue regeneration.J Clin Periodontol 1992;19:315-317.

2. Cortellini P, Pini-Prato G, Tonetti M. Periodontal regener-ation of human infrabony defects (V). Effect of oral hygieneon long-term stability. J Clin Periodontol 1994;21:606-610.

3. Cortellini P, Pini Prato GP, Tonetti MS. Long-term stabilityof clinical attachment following guided tissue regenera-tion and conventional therapy. J Clin Periodontol 1996;23:106-111.

4. Weigel C, Brägger U, Hämmerle CHF, Mombelli A, LangNP. Maintenance of new attachment 1 and 4 years fol-lowing guided tissue regeneration (GTR). J Clin Periodontol1995;22:661-669.

5. Cortellini P, Stalpers G, Pini Prato G, Tonetti MS. Long-term clinical outcomes of abutments treated with guidedtissue regeneration. J Prosthet Dent 1999;81:305-311.

6. De Sanctis M, Zucchelli G. Interleukin-1 gene polymor-phisms and long-term stability following guided tissueregeneration therapy. J Periodontol 2000;71:606-613.

7. Cortellini P, Tonetti MS. Long-term tooth survival fol-lowing regenerative treatment of intrabony defects. J Peri-odontol 2004; accepted for publication.

8. Newman MG, Caton J, Gunsolley JC. The use of the evi-dence-based approach in a periodontal therapy contem-porary science workshop. Ann Periodontol 2003;8:1-11.

SECTION MEMBERSJames T. Mellonig, Kevin G. Murphy, Reviewer

Group Leader Edward P. AllenMaurizio Tonetti, Chair Kenneth W. BueltmannDonald S. Clem, III, Pierpaolo Cortellini

Secretary J. Gary MaynardMichael MacNeil Robert G. SchallhornMichael K. McGuire Henry H. TakeiThomas Oates Raymond A. Yukna

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Guided Tissue Regeneration for the Treatment of … articles...included review of relevant bibliographies. Two manufacturers of GTR devices were contacted regarding unpub-lished data