Surgical Therapies for the Treatment of Gingival Recession. A Systematic Review

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1 Ann Periodontol Surgical Therapies for the Treatment of Gingival Recession. A Systematic Review Thomas W. Oates,* Melanie Robinson,* and John C. Gunsolley * Department of Periodontics, University of Texas Health Science Center at San Antonio, San Antonio, Texas. Department of Periodontics, Baltimore College of Dental Surgery, University of Maryland, Baltimore, Maryland. Background: A variety of soft tissue augmentation procedures directed at root coverage have been documented in the literature utilizing autogenous or allogenic soft tissue grafting or guided tissue regeneration (GTR). Rationale: The purpose of this systematic review was to assess the literature regarding the efficacies of various surgical gingival augmentation procedures relative to clinical and patient-oriented outcomes. Focused Question: What is the effect of surgical therapy for root coverage in patients with gingival recession compared with other treatment modalities or baseline values? Search Protocol: PubMed and the Cochrane Oral Health Group Trials Register were searched to identify human studies in English investigating the therapeutic use of a soft tissue surgical procedure to treat gingival recession. Searches were performed for articles published by April Selection Criteria: Initial screening of identified abstracts accepted all studies evaluating surgical intervention of gingival recession. Independent review by 2 reviewers evaluated full-text reports regarding study characteristics. Only those studies determined to be randomized clinical trials (RCTs) were included in the final analysis. Data Analysis and Collection: Outcome measures included changes in root coverage, clinical attachment levels (CAL), probing depth (PD), and width of keratinized tissue (KT). The only data suitable for metaanalysis were comparisons of the efficacy of connective tissue grafts with GTR. Main Results 1. Thirty-two articles (total study population: 687) met the criteria for RCTs: 11 (population: 286) related to various autogenous soft tissue augmentation procedures; 18 (population: 360) to GTR; and 3 (population: 41) to allogenic soft tissue augmentation. 2. Meta-analysis identified greater gains in both root coverage and keratinized tissue width for connective tissue graft procedures compared to GTR. 3. No other data were compatible with meta-analysis. Reviewers Conclusions 1. Soft tissue augmentation procedures are effective means of obtaining root coverage. 2. Connective grafting techniques appear to have an advantage over GTR. 3. There is a need for further efficacy studies and for investigation of these procedures relative to patientoriented outcomes such as esthetics, root sensitivity, and postoperative morbidities. Ann Periodontol 2003;8: KEY WORDS Grafts, soft tissue; guided tissue regeneration; tooth root/surgery; periodontal diseases/surgery; review literature; meta-analysis. 303

2 Surgical Treatment of Gingival Recession Volume 8 Number 1 December 2003 BACKGROUND Periodontal therapy has historically been directed primarily at the elimination of disease and the maintenance of a functional, healthy dentition and supporting tissues. However, more recently periodontal therapy, consistent with dental therapy in general, is increasingly directed at esthetic outcomes for patients, which extend beyond tooth replacement and tooth color to include the soft tissue component framing the dentition. Probably one of the most common esthetic concerns associated with the periodontal tissues is gingival recession. Gingival recession may be associated with anatomic factors, inflammatory conditions, or trauma. The progression of recession defects warrants both the investigation of etiologic factors and the consideration of therapeutic actions directed at minimizing the progression of the apical movement of the gingival margin. In many cases, these therapies directed at stopping the progression also enhance the esthetic appearance of the tissues. Root surface exposure resulting from gingival recession may also produce hypersensitivity; that is, a region of heightened temperature or tactile sensitivity along the exposed root surface. Covering the exposed root surface may decrease these symptoms. Additionally, there may be circumstances where recession defects create anatomic contours or a lack of keratinized tissue limiting proper plaque removal. Any of these indications, including esthetics, progression of the defect, hypersensitivity, or difficulties with oral hygiene may support the use of periodontal plastic surgical procedures. Periodontal plastic surgery includes periodontal surgical procedures performed to prevent, correct, or eliminate anatomical, developmental, traumatic, or plaqueinduced disease-related defects in the gingiva or alveolar mucosa. 1 The adoption of the plastic surgery terminology in itself suggests the increasing importance of the supporting tissues in the esthetics of the dentition. There are multiple periodontal plastic surgery approaches documented in the literature for the treatment of gingival recession defects. These treatment approaches generally include the manipulation of the patient s tissues to augment the soft tissues and cover the exposed root surface. Flap positioning allows for the maintenance of a vascular blood supply to the tissue, whereas a complete removal of autogenous graft tissue from intact vascular support to a distinct location requires the reformation of vascular supply to the grafted tissue. These grafting procedures may also take advantage of tissues procured in an allogeneic manner. More recently, the use of guided tissue regeneration (GTR) techniques have been utilized in re-establishing soft tissue dimensions over areas of recession. Each of these treatment approaches has been documented in the literature as having therapeutic benefit. There are multiple surgical techniques, materials, and root surface modification variables that may be considered, which complicate investigations relating to the effectiveness of these various approaches. RATIONALE The treatment options for soft tissue augmentation of gingival recession defects have been documented in numerous case reports and clinical investigations. A recent comprehensive review of this literature initially considered 590 articles related to this topic, selecting 216 for review. 1 This review failed to identify any significant treatment advantages of one surgical approach over the others. With the current trend toward evidencebased assessments of treatment, it becomes increasingly important for us to consider therapeutic outcomes relative to currently accepted treatment approaches. With the extensive literature available, it is difficult to assimilate these various studies into a meaningful policy. One approach toward achieving this assimilation of a large number of investigations is to perform a prospective, systematic review of the literature using well-defined criteria for inclusion of reports in the final considerations. FOCUSED QUESTION The purpose of this prospective systematic review was to assess the effectiveness of periodontal plastic surgery procedures in treating patients with gingival recession. Specifically, this assessment was to answer the following question: What is the effect of surgical therapy for root coverage in patients with gingival recession compared with other treatment modalities or baseline values? SEARCH PROTOCOL Data Sources and Search Strategies Initially, all identified references collected from 2 databases (PubMed, NCBI, National Library of Medicine and the Cochrane Oral Health Group) were screened to include only those human studies written in the English language investigating the therapeutic use of a soft tissue surgical procedure in the treatment of gingival recession. Search Strategy Database searches were conducted to identify studies with or as the connector between the following terms: gingival recession, gingival augmentation, mucogingival defect, mucogingival surgery, gingival graft, root coverage, and connective tissue graft. Publication cutoff date was April Inclusion criteria: Inclusion of articles was based on a careful review of the study title and abstract as to meeting the following eligibility criteria: human study, English language, and therapeutic study including the use of a gingival surgical procedure to treat gingival recession. 304

3 Ann Periodontol Oates, Robinson, Gunsolley Exclusion criteria: Reports clearly not meeting inclusion criteria were excluded, otherwise articles were considered in a secondary review. Screening Procedures Preliminary screening of identified studies included an independent assessment by the primary reviewer (TWO). Review of these references was based on title and abstract information. Secondary review of all identified references, conducted in an independent manner by the primary (TWO) and secondary (MR) reviewers, involved the review of full text versions of the studies identified in the initial screening. Each reviewer independently assessed studies for qualitative characteristics using a standardized assessment form (Fig. 1). All studies excluded by both reviewers were excluded from further consideration. Disagreements between examiners were resolved following joint review and discussion by the examiners. Only studies determined to be randomized controlled clinical trials (RCTs) were considered in the final analysis. I. Study Design: Randomized controlled clinical trial (RCT) Case-control (observational with control group) Case series (observational-no control group) II. Study Criteria: (need both of these: check if yes or not sure ) Human Therapeutic for gingival recession/root coverage III. If steps I and II above are met, proceed below: 1. What was test treatment? 2. What was control treatment? 3. Was it randomized? Yes no unsure 4. Method of randomization listed? Yes no unsure 5. Patients masked? Yes no unsure 6. Therapists masked? Yes no unsure 7. Examiners masked? Yes no unsure 8. Method of masking adequate? Yes no unsure 9. Prospective assessment? Yes no unsure 10. Retrospective assessment? Yes no unsure 11. Sequential cases? Yes no unsure 12. All cases accounted for? Yes no unsure 13. Outcome Measures Included: Defect types: Change in keratinized tissue Number of subjects Number of sites Follow-up period Number of teeth/patient Pretreatment defect dimensions Change in defect dimension Changes in root coverage Residual CAL/PD Changes in CAL/PD: Changes in gingival margin Subject assessments of: esthetics sensitivity other Figure 1. Form used for full article screening. Study participants: Studies included subjects having identified gingival recession defects of the soft tissue margin exposing the root surface of a tooth. Interventions. Surgical therapy interventions included all surgical therapies aimed at treating gingival recession defects and specifically included the use of autogenous and allogeneic soft tissue grafts and guided tissue regeneration procedures. Outcomes: Primary outcome measures included patient attitude toward defect, procedures, and results, including changes in esthetics, root surface sensitivity, and therapeutic morbidity. Additionally, surrogate measures included percentage of sites with complete root coverage, changes in gingival recession, probing depth (PD), clinical attachment levels (CAL), and amount of keratinized tissue. Data Collection and Analysis Quality appraisal. Studies were evaluated for randomization, masking, inclusion of control comparisons, and follow-up of subjects. Analysis. Study summary statistics included therapeutic modality, follow-up period, number of patients/ teeth, pretreatment defect dimensions, changes in defect dimensions and/or root coverage, residual PD, changes in CAL and gingival margin positions, and subject assessments of changes in esthetics or tooth sensitivity. Study groupings were based on therapeutic modalities investigated, outcomes measured, and quality of studies. Identification of 3 or more randomized controlled clinical studies comparing the same therapeutic modalities were considered for meta-analysis based on common outcome measures and levels of study quality. The only study information that was appropriate for metaanalysis was a comparison of the efficacy of connective tissue (CT) grafts with guided tissue regeneration procedures (GTR). The outcome variables assessed were amount of root coverage gained and keratinized tissue. Heterogeneity of results between studies was also assessed. The data were analyzed using a standardized 305

4 Surgical Treatment of Gingival Recession Volume 8 Number 1 December 2003 difference as described by Fleiss. 2 The results were checked with both a fixed effects model and a random effects model and the results were consistent. To test for heterogeneity both Cohens d (unadjusted) and Hedges s g (adjusted) were used. 3,4 Both tests had to be nonsignificant to support the lack of heterogeneity. RESULTS Initial application of described search strategies resulted in the identification of 1,434 reports that were eligible for screening. Initial screening by the primary reviewer identified 139 articles appropriate for full review by both reviewers Of these 139 articles, 32 were selected based on the criteria above for inclusion in this systematic review, with all but 2 articles included without discussion between reviewers to reach agreement. Of the 32 articles under review, 11 10,33,36,41,62,63,70,76,78,86,110 evaluated autogenous soft tissue grafting procedures, including coronally advanced flap procedures with or without free tissue augmentation, free gingival grafts, and connective tissue grafts using several technical approaches (Table 1). These studies were so inconsistent on the basis of interventions for both the experimental group and the control group that there were virtually no 2 studies alike. For that reason there was no quantitative analysis of the data. Eighteen 12,13,20,21,24,25,28,32,34,44,46,49,52,53,68,72,74,87 of the 32 articles evaluated GTR procedures aimed at soft tissue augmentation. These studies evaluated both bioabsorbable and non-resorbable materials (Table 2, page 308). The 3 remaining studies 9,14,18 evaluated the use of allogeneic soft tissue grafting materials (Table 3, page 310). The studies evaluated the effects of these various therapies from 3 months postsurgically to as long as 6 years. As may be expected, those studies with the longest follow-up period also had the greatest ranges in evaluation periods. The most consistent comparison among the studies was a control group of a connective tissue graft compared to a therapeutic group of GTR (9 studies 9,12,13,14,34,44,49,52,53 evaluated). A meta-analysis of this comparison was done (Fig 2, page 312.) Quality Assessment of Studies Overall, evaluation of the quality of the studies was very difficult due to the failure of many reports to provide sufficient information allowing for accurate assessment. Eleven of the 32 studies reported masked examiners and 5 studies clearly utilized sequentially enrolled subjects (see Tables 1, 2, and 3). Only randomized studies were included for this analysis. Methods of randomization for these studies varied from no mention of methods of randomization (but were Table 1. Autogenous Grafting Procedures* Intervention N N Examiner Sequential Reference Defect Type Subjects Defects Blinded? Cases Test Controls Borghetti & Louise Miller I-III N N CTG/double papillae None Bouchard et al Miller I-II N N CTG/CPF + TET CTG/CPF + CA Kennedy et al Mean rec = N N FGG None Mean rec = 1.0 Jahnke et al Miller I-II N N CGT/envelope FGG (thick) Trombelli et al N Y CPF-TET + fibrin glue CPF/TET; no fibrin glue Paolantonio et al Miller I-II N N CTG/CPF FGG Cordioli et al Miller I-II N Y CTG-envelope CTG/CPF Pini Prato et al Miller I-II >2m N N CPF + root polishing CPF + root planing Caffesse et al Miller I-II N N CTG/CPF + citric acid CTG/CPF; no CA Pini Prato et al Miller I >2m Y N CPF + tension CPF; no tension Bouchard et al Miller I-II N N CTG/CPF No CA + EPI collar CA; no EPI collar CTG/CPF * Only RCTs are included in this review; therefore, in accordance with previously reported classifications, all studies are ranked 1 (highest). 144 Yes (Y) or no or unsure (N). Abbreviations: CA = citric acid; CPF = coronally positioned flap; CTG = connective tissue graft; EPI = epithelial; FGG = free gingival graft; TET = tetracycline. 306

5 Ann Periodontol Oates, Robinson, Gunsolley included as a randomized study as long as suggestion of randomization was made in article) to complete randomization methodology descriptions. Of the 32 studies considered here, 17 failed to report some mechanism of randomization, and only 9 presented appropriate randomization mechanisms ,24,33,41,49,72,86 Subjective Evaluation of Therapies Seven of the 32 articles considered a subjective evaluation of the results regarding esthetics, root sensitivity, or patient preferences for individual procedures (Table 4, page 313) ,28,72,78,87 There was no standardization in the format of the results or in the methodology of these assessments. The findings ranged from general preference queries to the patients in split-mouth studies, to masked examiner assessments of procedures using a 4-point categorical assessment tool. The variability of the methods of assessment for these patient-oriented outcomes precluded our formal analysis of the results. However, evaluating the reported outcomes for each of these reports, there appeared to be consistent improvement of symptoms and esthetic concerns following root coverage procedures. Objective Evaluation of Therapies The only therapeutic comparisons providing information appropriate for meta-analysis were efficacy studies comparing autogenous connective tissue grafting with GTR or allogeneic graft procedures for the coverage of recession defects (Fig. 2). This comparison lent it self to meta-analysis since there were a sufficient number of studies (9) and the studies had 2 consistent outcome measures, change in keratinized tissue and change in recession. In evaluating the gain in root coverage between connective tissue (CT) grafts with GTR or allogeneic grafts, CT grafts had significantly (P = 0.012) greater gains in root coverage than did these other procedures. CT grafts had a mean (±SD) gain of 2.90 mm (±1.10) compared with a mean (±SD) gain of root coverage of 2.56 mm (±1.09) for the GTR with bioabsorbable membranes. A comparison of 2 studies using non-resorbable membranes found a similar relationship, with CT grafts providing a greater gain in root coverage than the GTR procedures. 52,53 In these studies, CT grafts produced 4.20 mm (±0.90) gain in root coverage, compared with a mean gain of 3.80 mm (±0.75) for GTR. The metaanalyses of these data are difficult to interpret. For the combined group of studies with bioabsorbable membranes and allogeneic grafts, there was a statistically significant (P = 0.041) difference between the 2 treatment groups. For the non-resorbable studies, the difference was not statistically significant (P = 0.309), but since there were only 2 studies with small sample sizes, there was not sufficient statistical power to find a difference. The test for heterogeneity was also significant, thus the results of these studies were inconsistent and it can be argued that they should not have been combined. However, 5 of these studies do show a trend favoring CT grafts, with 2 studies having a neutral effect, and only one using allogeneic grafts 9 favoring the alternative treatment. In evaluating the gain in width of keratinized tissue comparing connective tissue (CT) grafts with GTR or allogeneic grafts, 7 of the previously mentioned studies had data which could be evaluated (Fig. 3, page 313). 9,12,14,44,49,52,53 CT grafts had significantly greater (P = 0.002) gains in keratinized tissue than did these other procedures. This difference is evident in the metaanalysis as all the studies considered favored CT grafts regarding gains in KT. CT grafts had a mean gain of 1.33 mm (±1.19) compared to a mean gain of keratinized tissue of 0.48 mm (±1.03) for the GTR using bioabsorbable membranes. A similar comparison with 2 studies using non-resorbable membranes found a similar relationship with CT grafts providing a greater gain in keratinized tissue than the GTR procedures. 52,53 In these studies, CT grafts produced 2.30 mm (±0.90) gain in KT, compared with a mean gain of 0.50 mm (±1.01) for GTR. However, this difference was not statistically significant (P = 0.158) due to the heterogeneity and small number of studies under consideration. The analysis of the data was similar to the previous analysis with a significant (P <0.05) difference for the bioabsorbable membranes or allogeneic grafts providing less keratinized tissue than the connective tissue groups. The test for heterogeneity was again statistically significant. However, in this case the reason for the inconsistence was that the gains for the connective tissue grafts varied in the degree by which the connective tissue grafts outperformed the GTR approach. Since all of the 7 studies favored the connective tissue grafts, the studies were combined and the subsequent metaanalysis supported the superiority of the connective tissue graft. GTR Procedures Overall, this review identified 18 studies in which GTR procedures were assessed for treatment of gingival recession defects. The GTR procedures in these studies utilized either bioabsorbable or non-resorbable materials. The comparative treatments in these studies included either autogenous tissue grafting procedures or alternative GTR membranes. In addition to metaanalysis, observations were made regarding clinical attachment levels and probing depths for all studies presenting appropriate data. Evaluation of mean root coverage for 17 of these 18 studies utilizing GTR procedures found 76.4 (±11.3)% root coverage, with 100% root coverage at 33.1 (±20.4)% of the sites. These findings compare with various autogenous grafting procedures which served as controls with mean root cov- 307

6 Surgical Treatment of Gingival Recession Volume 8 Number 1 December 2003 Table 2. GTR Procedures* Examiner Reference Defect Type N Subjects N Defects Masked? Sequential Cases? Tatakis & Trombelli Miller I, II; 2mm Y Y Amarante et al Miller I, II; 3mm Y N Borghetti et al Miller I; 2mm N N Romagna-Genon Miller I, II N Y Dodge et al Miller I, II; 3mm Y N Ito et al Miller I, II; 4mm 6 8 N N Pini Prato et al Miller I, II; 3mm N N Jepsen et al MIller I, II N N Zucchelli et al Miller I, II; 5mm Y Y Trombelli et al Miller I, II N N Trombelli et al Miller I, II; 4mm 8 16 Y N Rosetti et al Miller I, II; (3-5 mm) Y N Pini Prato et al mm N N Wang et al Miller I, II; 3mm Y N Duval et al Miller I, II; 3mm N N Modica et al Miller I, II Y N 308

7 Ann Periodontol Oates, Robinson, Gunsolley Table 2. (continued) GTR Procedures* Mean Results Study Root Root Interventions Duration Coverage Coverage Test Controls (months) mm % 100% CAL PD KT GTR/Bioab (PLA) CTG/CPF GTR/Bioab (PLA) CPF (no membrane) GTR/Bioab (PLA) CTG/CPF GTR/Bioab (Por coll) CTG/CPF GTR/Bioab (PLA) PLA910 + DFDBA GTR/Bioab (PLA) GTR/Non-res (eptfe) FGG GTR/Non-res (eptfe) FGG + CPF (2-step) GTR/Non-res (TR-ePTFE) + TET CTG/envelope + TET GTR/Bioab (Por coll) GTR/Non-res (eptfe) CTG/CPF GTR/Bioab (PLA/PGA) CTG/CPF GTR/Non-res (eptfe) TET/FN/FBN GTR/Non-res (eptfe) GTR/Bioab (coll) DFDBA CTG/CPF GTR/non-res (eptfe) FGG + CPF (2-step) GTR/Bioab (coll) CTG/CPF GTR/Bioab (PLA) DFDBA GTR/Bioab (PLA) CPF + EMD CPF (continued) 309

8 Surgical Treatment of Gingival Recession Volume 8 Number 1 December 2003 Table 2. (continued) GTR Procedures* Examiner Reference Defect Type N Subjects N Defects Masked? Sequential Cases? Roccuzzo et al Miller I, II; 4mm N N Matarasso et al Miller I, II; >3mm N N * Only RCTs are included in this review; therefore, in accordance with previously reported classifications, all studies are ranked 1 (highest). 144 Yes (Y) or no or unsure (N). Abbreviations: Biob = bioabsorbable membrane; Coll = collagen; CPF = coronally positioned flap; CTG = connective tissue graft; DFDBA = demineralized freeze-dried bone allograft; DPF = double pedicle flap; EMD = enamel matrix derivative; eptfe = expanded polytetrafluoroetheylene; FGG = free gingival graft; FBN = fibronectin; FN = fibrin; Non-res = non-resorbable membrane; PLA = polylactic acid; PLA/PGA = polylactic/polygycolic acid- PLA 910 = polyglactin 910- Por coll = porcine collagen; TET = tetracycline; TR = titanium-reinforced. Table 3. Allogeneic Soft Tissue Grafts* Interventions Defect N N Examiner Sequential Reference Type Subjects Defects Masked? Cases? Test Controls Novaes et al Miller I, II 9 30 N N Allogeneic graft Aichelmann-Reidy et al. 14 Miller I, II Y N Allogeneic graft mm CTG CTG against tooth Henderson et al Miller I, II Y N Allogeneic graft + 3mm CPF/basement membrane against tooth * Only RCTs are included in this review; therefore, in accordance with previously reported classifications, all studies are ranked 1 (highest). 144 Yes (Y) or no or unsure (N). Abbreviations: CPF = coronally positioned flap; CT = connective tissue; CTG = connective tissue graft. Allogeneic graft + CPF/ CT side against tooth erage of 81.9 (±9.8)%, with 42.2 (±23.6)% of the sites having 100% root coverage. Using GTR procedures, mean (±SD) gains in clinical attachment levels were 3.20 (±1.14) mm based on 16 of the 18 studies. Changes in probing depths were minimal for all 18 studies (mean: 0.53 ± 0.41 mm) and may be reflective of the shallow probing depth identified at baseline (mean: 1.54 mm). Autogenous Tissue Grafts In comparing the studies meeting the criteria set forth in this analysis, 11 studies were identified in which autogenous tissue grafting procedures were assessed (Table 1). 10,33,35,41,62,63,70,76,78,86,110 These procedures included connective tissue grafting using various techniques (e.g., coronally positioned, double papillae, or envelope flap) and adjunctive materials (e.g., fibrin glue, citric acid, or tetracycline). They also assessed the levels of tension on the flap and the need for root planing versus root polishing. None of these studies allowed for consideration using meta-analysis. However, observations were made regarding reduction in recession, clinical attachment levels, probing depths, and gains in keratinized tissues. Reductions in recession 310

9 Ann Periodontol Oates, Robinson, Gunsolley Table 2. (continued) GTR Procedures* Mean Results: Study Root Root Interventions Duration Coverage Coverage Test Controls (months) mm % 100% CAL PD KT GTR/Bioab eptfe GTR/Bioab (PLA) GRT/Bioab (PLA) DPF CPF Table 3. (continued) Allogeneic Soft Tissue Grafts* Results Study Root Coverage Duration (months) mm % 100% CAL PD KT defects showed a mean gain of 2.46 (±0.61) mm. When excluding the one and only study 110 using free gingival grafts as a test intervention, with a mean reduction of 0.3 mm, the mean gain in root coverage for the remaining 10 studies was 2.68 (±0.45) mm. The mean percentage of root coverage for these 10 studies was 77.9 (±10.0)% root coverage, with 100% root coverage 37.4 (±19.4)% for procedures utilizing connective tissue grafting and/or coronally positioned flaps. These findings appear favorable compared with free gingival grafts in 2 studies. 63,86 The mean root coverage was 48.1 (±7.2)%, with 9.3 (±1.0)% of sites having 100% root coverage. The mean gain in CAL level was 2.33 (±0.80) mm when considering all 11 studies and 2.62 (±0.68) mm when excluding the free gingival graft data. Changes in mean PD were minimal for all studies, 0.11 (±0.32) mm, and may be reflective of the shallow probing depth identified at baseline, 1.33 (±0.23) mm. Evaluating the mean gain in keratinized tissue showed an increase of 1.85 (±1.05) mm, with the free gingival grafting study 110 having the greatest increase (4.9 mm). Excluding this study, the mean gain in keratinized tissue was 1.52 (±0.96) mm. Allogeneic Tissue Grafts In comparing the studies meeting the criteria set forth in this systematic review, 3 studies 9,14,18 were identified in which allogeneic tissue grafting procedures were assessed (see Table 3). The grafts utilized in each of these studies were allogeneic dermal connective tissue matrix grafts. These studies did not allow for consideration using meta-analysis. However, certain observations were made using the 2 studies in which autogenous CT grafting was compared, 9,14 including reduction in recession, clinical attachment levels, and probing depths, and gains in keratinized tissue. Reductions in recession defects using allogeneic grafts showed a mean gain of 1.90 (±0.28) mm and mean changes in clinical attachment levels of 1.15 (±0.49) mm. This change equaled 65.5 (±0.71)% root coverage. This compared with autogenous connective tissue grafting, in which reductions in recession defects showed a mean gain of 2.05 (±0.18) mm, or 67.3 (±6.11)% root coverage, and a mean change in clinical attachment level of 1.34 (±0.36) mm. 9,14 Changes in probing depths were minimal for all studies, mean increase of 0.19 (±0.31) mm, and may be reflective of the shallow mean probing depth identified at baseline, 1.20 (±0.13) mm. Evaluating the mean gain in keratinized tissue showed an increase of 0.92 (±0.40) mm with allogeneic tissue 311

10 Surgical Treatment of Gingival Recession Volume 8 Number 1 December 2003 Figure 2. Comprehensive meta-analysis of recession comparing autogenous connective tissue grafting with GTR procedures. Abbreviations: Coll = collagen; eptfe = expanded polytetrafluoroethylene; PLA = polylactic acid; PLA/PGA = polylactic/polyglycolic acid; Por coll = porcine collagen. grafting compared with 1.35 (±0.22) mm in autogenous connective tissue grafting. 9,14 DISCUSSION The results of the meta-analyses in this review identified statistically greater reductions in gingival recession and gains in keratinized tissue utilizing autogenous connective tissue grafts compared with guided tissue regeneration procedures. This result is interesting in that the identified differences found in this meta-analysis were based on a series of individual studies in which a significant difference was not detected. Unfortunately, inconsistencies between studies did not permit similar analyses of study comparisons between various aspects of autogenous soft tissue grafting procedures nor between procedures using allogeneic grafting procedures. An additional shortcoming with the majority of the reviewed studies was a general insufficiency in presenting study parameters. In evaluating the studies meeting our inclusion criteria, there was a minority of reports that had identified methods of randomization that were viewed as adequate, such as randomization lists or coin toss. The majority of the reports did not identify the method of randomization, but merely noted that randomization was performed as part of the study design. Three studies listed as randomized utilized alternating patterns for randomization. These studies, and those without any specific description of method of randomization, were included in these analyses. Similarly, only 11 studies 12,14,18,21,24,28,32,34,36,53,74 reported that the examiners were masked as to the treatment provided. None of the studies reported any masking of the patient or the individual providing the therapies. These deficiencies may be viewed as a limitation of this current analysis of the literature. The evaluated studies included 2 investigations comparing autogenous tissue grafting to no treatment. 44,110 These 2 studies were consistent in demonstrating the potential for either free gingival grafting or connective tissue grafting to successfully augment keratinized tissue; however the control conditions demonstrated little change over extended evaluations as long as 12 to 72 months. These findings do support the potential for stability with recession defects having little keratinized tissues. Soft tissue augmentation procedures have multiple indications including esthetics, prevention of the progression of the recession defect, hypersensitivity, and anatomic deficiencies that may affect tissue health. Treatment based on these indications may be addressed with the goals of obtaining an increased zone of keratinized tissue and root coverage. It is clear that these studies demonstrate a wide range of root coverage success. The mean levels of root coverage obtained were between 73 to 80% for the 3 general treatment groupings, but the ranges reported from individual studies varied from 48 to 91%, thus raising some question as to the predictability of these procedures. One of the most utilized methods in the reviewed studies to quantify this predictability was by measuring the 312

11 Ann Periodontol Oates, Robinson, Gunsolley Table 4. Patient Centered Outcomes Intervention Reference Test Control Results Romagna-Genon 13 GTR/Bioab CTG/CPF Width of recession defect was reduced more in control than 2001 (Por coll) test defects, all control patients complained of soreness at donor site Rosetti et al GTR/Bioab CTG/CPF Patients satisfied with result ( good ) for CT graft (80%) and (coll) + DFDBA GTR (82%) Wang et al GTR/Bioab (coll) CTG/CPF Examiner: 15/16 excellent color for GTR; 16/16 excellent or good color for CT graft Patient: 14/16 exellcent or good for both treatments Roccuzzo et al. 72 GTR/Bioab eptfe Postoperative pain, swelling, esthetics similar between groups 1996 GTR/bioab preferred due to 1 sx-(no statistics shown) Aichelmann- Allogeneic CTG Both patient and clinician evaluations: significantly greater fre- Reidy et al quency of excellent appearance scores with allogeneic graft Pini Prato et al. 87 GTR/non-res FGG + CPF 4/25 patients in test group with baseline root hypersensitivity; 1992 (eptfe) (2 step) 0/25 postoperatively 0/25 patients in control group with root hypersensitivity at baseline and postoperatively Bouchard et al. 78 CTG/CPF No CA + EPI Examiner: 20/30 had good esthetic result and 10/ collar moderate esthetic result CA; no EPI collar CTG/CPF 5/30 patients with baseline root hypersensitivity; 0/30 postoperatively Abbreviations: Bioab = bioabsorbable membrane; Coll = collagen; CPF = coronally positioned flap; CTG = connective tissue graft; DFDBA = demineralized freeze-dried bone allograft; EPI = epithelial; eptfe = expanded polytetrafluoroetheylene; FGG = free gingival graft; Non-res = non-resorbable membrane. Figure 3. Comprehensive meta-analysis of gains in keratinized tissue comparing autogenous connective tissue grafting with GTR procedures. Abbreviations: Coll = collagen; eptfe = expanded polytetrafluoroethylene; PLA = polylactic acid; PLA/PGA = polylactic/polyglycolic acid; Por coll = porcine collagen. 313

12 Surgical Treatment of Gingival Recession Volume 8 Number 1 December 2003 incidence of achieving 100% root coverage following the tested treatment. The results for percentage of sites with 100% root coverage varied widely for the 3 treatment groups, from 33 to 52%. The mean ranges reported within the individual studies varied from 8 to 70%. These ranges suggest there are numerous factors that may influence treatment success using procedures directed at root coverage. Many of the technical and therapeutic factors have been evaluated through the efforts of individual investigations. However, there is no single factor or group of factors that have been identified to explain this variance. Based on the limited assessments of the 7 reviewed studies in which patient-oriented outcomes were assessed, 12-14,28,72,78,87 each of these surgical options appears to have positive effects. Three studies addressed esthetic results 12,14,28 and showed definite improvements with treatment. One study 72 found that there was difference in postoperative morbidities and esthetics between bioabsorbable and non-resorbable membranes. The findings of 2 additional studies support the use of these procedures to reduce root hypersensitivity. 78,87 Although postoperative discomfort was demonstrable in study surveys, at least in association with palatal connective tissue donor sites, the level of discomfort appears minimal. 13,14 The evaluation of these reports in the present analysis was based on the assessment of soft tissue augmentation procedures aimed at root coverage. These procedures were classified as using autogenous or allogeneic tissue graft materials with any of several manipulative approaches or the use of GTR procedures. The use of GTR represents an interesting shift in the treatment paradigm for GTR procedures typically associated with intrabony defects rather than soft tissue defects. From our investigation it is clear that considerable research effort has gone into investigating the efficacy of this treatment approach. It is therefore significant that the present study found the GTR approach did not provide the same levels of root coverage and gains in keratinized tissues that are associated with the more traditional soft tissue augmentation approaches. It is also of interest to note that this analysis included a single study utilizing a non-barrier technique in the GTR group. 24 This classification was based on the proposed effects of the enamel matrix protein extract to stimulate specific patterns of cellular proliferation and differentiation. This non-barrier GTR study compared coronally positioned flap surgery with or without enamel matrix extract treatment and failed to find a significant difference in percentages of root coverage obtained, although mean values for percentage of root coverage were greater with the addition of the extract. 24 This finding is consistent with a recent report that compared the use of the enamel protein extract application or connective tissue grafts in conjunction with coronally positioned flap procedures. 145 This study showed that there was no difference in the amounts of root coverage obtained between treatment approaches. In addition, there was less keratinized tissue resulting from this nonbarrier GTR procedure, consistent with our meta-analysis for GTR procedures using barrier techniques compared with connective tissue grafting procedures. In summary, the overall goal of this study to assess both clinical and patient-oriented outcomes using a prospectively designed systematic analysis was only partially achieved. Wide variations in results obtained and in techniques utilized impacted on our ability to accomplish this goal. However, this in itself may be a significant finding regarding our current state of knowledge and the high level of difficulty in effectively synthesizing reports into clinical decisions. Hopefully, analyses of the literature such as this will provide guidance for future studies directed at the evidence-based assessment of therapy. REVIEWERS CONCLUSIONS 1. The systematic review of the data demonstrates there are several surgical procedures that successfully cover exposed root surfaces. There is evidence that these surgical procedures result in improved patientoriented outcomes including decreased root sensitivity and enhanced soft tissue esthetics. 2. Meta-analysis identified statistically significant advantages for autogenous connective tissue grafts when compared with GTR using bioabsorbable barriers in terms of root coverage and width of keratinized tissue. 3. A limited number of recent randomized controlled studies support the efficacy of coronally positioned flaps with allogeneic soft tissue grafts for root coverage. 4. The studies identified in this systematic review concerning patient-oriented outcomes lacked standardization of measures, precluding quantitative analysis. FUTURE DIRECTIONS FOR PRACTICE AND RESEARCH 1. Future studies designed primarily to investigate patient-oriented outcomes such as esthetics, hypersensitivity, morbidities, and overall satisfaction are needed. 2. Most of the literature dealing with root coverage procedures consists of case series and non-randomized studies. Future well-designed investigations are needed to further clarify the relative efficacy of different treatment options. 3. Based on the number of studies using autogenous connective tissue grafts in conjunction with coronally positioned flap surgery, it is surprising there are no comparative randomized controlled clinical trials for this treatment and coronally positioned flap surgery alone. Future studies are needed to assess the effi- 314

13 Ann Periodontol Oates, Robinson, Gunsolley cacy of coronally positioned flap procedures in the presence or absence of connective tissue grafting. ACKNOWLEDGMENTS The authors extend their appreciation to Ms. Madgeline Cluck for her untiring assistance throughout the development of this report. REFERENCES 1. Wennström JL. Mucogingival therapy. Ann Periodontol 1996;1: Fleiss JL. The statistical basis of meta-analysis. Stat Methods Med Res 1993;2(2): Katerndahl DA, Cohen PA. Quantitatively reviewing the literature: The application of meta-analysis. Fam Pract Res J 1987;6(3): Heges L, Olkin I. Statistical Methods of Meta-Analysis. Orlando: Academic Press; Hägewald S, Spahr A, Rompola E, Haller B, Heijl L, Bernimoulin J-P. Comparative study of Emdogain and coronally advanced flap technique in the treatment of human gingival recessions. A prospective controlled clinical study. J Clin Periodontol 2002;29: Müller H-P, Stahl M, Eger T. Failure of root coverage of shallow gingival recessions employing GTR and a bioresorbable membrane. Int J Periodontics Restorative Dent 2001;21: Tinti C, Manfrini F, Parma-Benfenati S. A bioresorbable barrier in the treatment of gingival recession: Description of a new resorbable dome device. Int J Periodontics Restorative Dent 2001;21: Hirsch A, Attal U, Chai E, Goultschin J, Boyan BD, Schwartz Z. Root coverage and pocket reduction as combined surgical procedures. J Periodontol 2001;72: Novaes AB Jr, Grisi DC, Molina GO, Souza SLS, Taba M Jr, Grisi MFM. Comparative 6-month clinical study of a subepithelial connective tissue graft and acellular dermal matrix graft for the treatment of gingival recession. J Periodontol 2001;72: Cordioli G, Mortarino C, Chierico A, Grusovin MG, Majzoub Z. Comparison of 2 techniques of subepithelial connective tissue graft in the treatment of gingival recessions. J Periodontol 2001;72: Nelson SW. Subperiosteal and intraosseous connective tissue grafts for pocket reduction: A 9- to 13-year retrospective case series report. J Periodontol 2001;72: Wang H-L, Bunyaratavej P, Labadie M, Shyr Y, MacNeil RL. Comparison of 2 clinical techniques for treatment of gingival recession. J Periodontol 2001;72: Romagna-Genon C. Comparative clinical study of guided tissue regeneration with a bioabsorbable bilayer collagen membrane and subepithelial connective tissue graft. J Periodontol 2001;72: Aichelmann-Reidy ME, Yukna RA, Evans GH, Nasr HF, Mayer ET. Clinical evaluation of acellular allograft dermis for the treatment of human gingival recession. J Periodontol 2001;72: Harris RJ. Clinical evaluation of 3 techniques to augment keratinized tissue without root coverage. J Periodontol 2001;72: Harris RJ. Histologic evaluation of root coverage obtained with GTR in humans: A case report. Int J Periodontics Restorative Dent 2001;21: Saletta D, Pini Prato G. Pagliaro U. Baldi C. Mauri M. Nieri M. Coronally advanced flap procedure: Is the interdental papilla a prognostic factor for root coverage? J Periodontol 2001;72: Henderson RD, Greenwell H, Drisko C, et al. Predictable multiple site root coverage using an acellular dermal matrix allograft. J Periodontol 2001;72: Jorgic-Srdjak K, Bosnjak A, Plancak D, Maricevic T. Ten-year evaluation of conservative and surgical treatment of gingival recession. A case series study. Coll Antropol 2000;24: Ito K, Oshio K, Shiomi N, Murai S. A preliminary comparative study of the guided tissue regeneration and free gingival graft procedures for adjacent facial root coverage. Quintessence Int 2000;31: Dodge JR, Greenwell H, Drisko C, Wittwer JW, Yancey J, Rebitski G. Improved bone regeneration and root coverage using a resorbable membrane with physically assisted cell migration and DFDBA. Int J Periodontics Restorative Dent 2000;20: Harris RJ. A comparative study of root coverage obtained with an acellular dermal matrix versus a connective tissue graft: Results of 107 recession defects in 50 consecutively treated patients. Int J Periodontics Restorative Dent 2000;20: Maurer S, Hayes C, Leone C. Width of keratinized tissue after gingivoplasty of healed subepithelial connective tissue grafts. J Periodontol 2000;71: Modica F, Del Pizzo M, Roccuzzo M, Romagnoli R. Coronally advanced flap for the treatment of buccal gingival recessions with and without enamel matrix derivative. A split-mouth study. J Periodontol 2000;71: Duval BT, Maynard JG, Gunsolley JC, Waldrop TC. Treatment of human mucogingival defects utilizing a bioabsorbable membrane with and without a demineralized freeze-dried bone allograft. J Periodontol 2000;71: Boltchi FE. Allen EP. Hallmon WW. The use of a bioabsorbable barrier for regenerative management of marginal tissue recession. I. Report of 100 consecutively treated teeth. J Periodontol 2000;71: Zucchelli G, De Sanctis M. Treatment of multiple recession-type defects in patients with esthetic demands. J Periodontol 2000;71: Rosetti EP, Marcantonio RAC, Rossa C Jr, Chaves ES, Goissis G, Marcantonio E Jr. Treatment of gingival recession: Comparative study between subepithelial connective tissue graft and guided tissue regeneration. J Periodontol 2000;71: Jepsen S, Heinz B, Kermanie MA, Jepsen K. Evaluation of a new bioabsorbable barrier for recession therapy: A feasibility study. J Periodontol 2000;71: Greenwell H, Bissada NF, Henderson RD, Dodge JR. The deceptive nature of root coverage results. J Periodontol 2000;71: Wei P-C, Laurell L, Geivelis M, Lingen MW, Maddalozzo D. Acellular dermal matrix allografts to achieve increased attached gingiva. Part 1. A clinical study. J Periodontol 2000;71: Amarante ES, Leknes KN, Skavland J, Lie T. Coronally positioned flap procedures with or without a bioabsorbable membrane in the treatment of human gingival recession. J Periodontol 2000;71: Caffesse RG, De La Rosa M, Garza M, Munne-Travers A, Mondragon JC, Weltman R. Citric acid demineralization and subepithelial connective tissue grafts. J Periodontol 2000;71:

14 Surgical Treatment of Gingival Recession Volume 8 Number 1 December Tatakis DN, Trombelli L. Gingival recession treatment: Guided tissue regeneration with bioabsorbable membrane versus connective tissue graft. J Periodontol 2000; 71: Pini Prato G, Pagliaro U, Baldi C, et al. Coronally advanced flap procedure for root coverage. Flap with tension versus flap without tension: A randomized controlled clinical study. J Periodontol 2000;71: Pini Prato G, Baccetti T, Magnani C, Agudio G, Cortellini P. Mucogingival interceptive surgery of buccally-erupted premolars in patients scheduled for orthodontic treatment. I. A 7-year longitudinal study. J Periodontol 2000; 71: Müller H-P, Stahl M, Eger T. Dynamics of mucosal dimensions after root coverage with a bioresorbable membrane. J Clin Periodontol 2000;27: Zabalegui I, Sicilia A, Cambra J, Gil J, Sanz M. Treatment of multiple adjacent gingival recessions with the tunnel subepithelial connective tissue graft: A clinical report. Int J Periodontics Restorative Dent 1999;19: Carnio J, Miller PD Jr. Increasing the amount of attached gingiva using a modified apically repositioned flap. J Periodontol 1999;70: Baldi C, Pini-Prato G, Pagliaro U, et al. Coronally advanced flap procedure for root coverage. Is flap thickness a relevant predictor to achieve root coverage? A 19-case series. J Periodontol 1999;70: Pini-Prato G, Baldi C, Pagliaro U, et al. Coronally advanced flap procedure for root coverage. Treatment of root surface: Root planing versus polishing. J Periodontol 1999;70: Müller H-P, Stahl M, Eger T. Root coverage employing an envelope technique or guided tissue regeneration with a bioabsorbable membrane. J Periodontol 1999;70: Tatakis DN. Trombelli L. Adverse effects associated with a bioabsorbable guided tissue regeneration device in the treatment of human gingival recession defects. A clinicopathologic case report. J Periodontol 1999;70: Borghetti A, Glise J-M, Monnet-Corti V, Dejou J. Comparative clinical study of a bioabsorbable membrane and subepithelial connective tissue graft in the treatment of human gingival recession. J Periodontol 1999;70: Milano F. A combined flap for root coverage. Int J Periodontics Restorative Dent 1998;18: Matarasso S, Cafiero C, Coraggio F, Vaia E, de Paoli S. Guided tissue regeneration versus coronally repositioned flap in the treatment of recession with double papillae. Int J Periodontics Restorative Dent 1998;18: Harris RJ. A comparison of 2 root coverage techniques: Guided tissue regeneration with a bioabsorbable matrix style membrane versus a connective tissue graft combined with a coronally positioned pedicle graft without vertical incisions. Results of a series of consecutive cases. J Periodontol 1998;69: Scabbia A, Trombelli L. Long-term stability of the mucogingival complex following guided tissue regeneration in gingival recession defects. J Clin Periodontol 1998;25: Trombelli L, Scabbia A, Tatakis DN, Calura G. Subpedicle connective tissue graft versus guided tissue regeneration with bioabsorbable membrane in the treatment of human gingival recession defects. J Periodontol 1998;69: Zahedi S, Bozon C, Brunel G. A 2-year clinical evaluation of a diphenylphosphorylazide-cross-linked collagen membrane for the treatment of buccal gingival recession. J Periodontol 1998;69: Müller H-P, Eger T, Schorb A. Gingival dimensions after root coverage with free connective tissue grafts. J Clin Periodontol 1998;25: Jepsen K, Heinz B, Halben JH, Jepsen S. Treatment of gingival recession with titanium reinforced barrier membranes versus connective tissue grafts. J Periodontol 1998;69: Zucchelli G, Clauser C, De Sanctis M, Calandriello M. Mucogingival versus guided tissue regeneration procedures in the treatment of deep recession type defects. J Periodontol 1998;69: Mendes DN, Novaes AB Jr, Novaes AB. Root coverage of large localized gingival recession: A biometric study. Braz Dent J 1997;8: Ozcan G, Kurtis B, Balos K. Combined use of root conditioning, fibrin-fibronectin system and a collagen membrane to treat a localized gingival recession: A 10-case report. J Marmara Univ Dent Fac 1997;2: Trombelli L, Tatakis DN, Scabbia A, Zimmerman GJ. Comparison of mucogingival changes following treatment with coronally positioned flap and guided tissue regeneration procedures. Int J Periodontics Restorative Dent 1997;17: Waterman CA. Guided tissue regeneration using a bioabsorbable membrane in the treatment of human buccal recession. A re-entry study. J Periodontol 1997;68: Harris RJ. Creeping attachment associated with the connective tissue with partial-thickness double pedicle graft. J Periodontol 1997;68: Harris RJ. A comparative study of root coverage obtained with guided tissue regeneration utilizing a bioabsorbable membrane versus the connective tissue with partial-thickness double pedicle graft. J Periodontol 1997;68: Shieh A-T, Wang H-L, O Neal R, Glickman GN, MacNeil RL. Development and clinical evaluation of a root coverage procedure using a collagen barrier membrane. J Periodontol 1997;68: Trombelli L, Scabbia A. Healing response of gingival recession defects following guided tissue regeneration procedures in smokers and non-smokers. J Clin Periodontol 1997;24: Bouchard P, Nilvéus R, Etienne D. Clinical evaluation of tetracycline HCl conditioning in the treatment of gingival recessions. A comparative study. J Periodontol 1997;68: Paolantonio M, di Murro C, Cattabriga A, Cattabriga M. Subpedicle connective tissue graft versus free gingival graft in the coverage of exposed root surfaces. A 5-year clinical study. J Clin Periodontol 1997;24: Ricci G, Silvestri M, Rasperini G, Cattaneo V. Root coverage: A clinical/statistical comparison between subpedicle connective tissue graft and laterally positioned full thickness flaps. J Esthetic Dent 1996;8: Ricci G, Silvestri M, Tinti C, Rasperini G. A clinical/ statistical comparison between the subpedicle connective tissue graft method and the guided tissue regeneration technique in root coverage. Int J Periodontics Restorative Dent 1996;16: De Sanctis M, Zucchelli G. Guided tissue regeneration with a resorbable barrier membrane (Vicryl) for the management of buccal recession: A case report. Int J Periodontics Restorative Dent 1996;16: Wang H-L, MacNeil RL, Shieh A-T, O Neal R. Utilization 316

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