J Clin Periodontol 2012; 39: 145156 doi: 10.1111/j.1600-051X.2011.01815.

Clinical performance of access ap surgery in the treatment of the intrabony defect. A systematic review and meta-analysis of randomized clinical trials
Graziani F, Gennai S, Cei S, Cairo F, Baggiani A, Miccoli M, Gabriele M, Tonetti M. Clinical performance of access ap surgery in the treatment of the intrabony defect. A systematic review and meta-analysis of randomized clinical trials. J Clin Periodontol 2012; 39: 145156. doi: 10.1111/j.1600-051X.2011.01815.x. Abstract Aim: To systematically review the literature and to determine the clinical performance of conservative surgery (CS) for the treatment of intrabony defects (ID). Methods: RCTs on ID treatment with 12 months of follow-up were identied through electronic databases and hand-searched journals. Primary outcomes were tooth survival, clinical attachment (CAL) gain, probing depth (PD) reduction and gingival recession increase (REC). Weighted means and forest plots were calculated for each outcome variable 12 months after surgery. Long-term stability was explored with RCTs of at least 24 months of follow-up. Subgroup analysis was performed according to the type of ap. Results: Twenty-seven trials reporting 647 subjects and 734 defects were identied. Twelve months after CS, tooth survival was 98% (IQ: 96.77100), CAL gain 1.65 mm (95% CI: 1.371.94; p < 0.0001), PD reduction 2.80 mm (CI: 2.433.18; p < 0.0001) and REC increase 1.26 mm (CI: 0.941.49; p < 0.0001). Longer follow-up showed similar ndings. CI of CAL gain were 1.443.52 for recently introduced papilla preservation aps and 1.251.89 mm for access aps. Conclusions: The treatment of intrabony defect with CS is associated with high tooth retention and improvement of periodontal clinical parameters. Clinical performance may vary according to the type of surgical ap used.

Filippo Graziani1, Stefano Gennai1, Silvia Cei1, Francesco Cairo2, Angelo Baggiani3, Mario Miccoli3, Mario Gabriele1 and Maurizio Tonetti4
1

Department of Surgery, Unit of Dentistry and Oral Surgery, University of Pisa, Pisa, Italy; 2 Department of Periodontology, University of Florence, Florence, Italy; 3Department of Experimental Pathology, Medical Biotechnologies, Infectious Diseases and Epidemiology, University of Pisa, Pisa, Italy; 4 European Research Group on Periodontology, Genova, Italy

Key words: access ap; intrabony defects; meta-analysis; papilla preservation ap Accepted for publication 13 September 2011

Conict of interest and source of funding statement The authors declare that they have no conict of interests. This study has been self-supported by the authors and their institution.
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Periodontal osseous lesions associated with deep pockets are frequent anatomical sequelae to periodontitis (Papapanou & Tonetti 2000). After successful cause-related therapy, the surgical treatment of persisting pockets is suggested to re-establish a periodontal anatomy able to sustain

periodontal health after treatment (Lang 2000). Surgical cleansing of the defect and the root surface can re-establish periodontal health when proper plaque control is established (Rosling et al. 1976a). However, dierent surgical techniques have been advocated

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Reporting Items for Systematic Review and Meta-Analyses) statement (Liberati et al. 2009, Moher et al. 2009). The systematic review was designed to answer the following focused question: which is the rate of tooth survival and clinical attachment level (CAL) gain probing pocket depth (PPD) reduction and gingival recession (REC) increase of teeth aected by periodontitis-related intrabony defect, 12 months after conservative periodontal surgery as documented in randomized clinical trials comparing it with other surgical options? Only RCTs comparing conservative surgery versus other surgical interventions on periodontal intrabony defects were included. Selected studies showed at least 12 months of follow-up and included at least 10 subjects. No language limitations were applied.
Information sources and search

to conservatively treat intrabony defects. Conservative surgery (CS) consists therefore of a number of different surgical procedures aimed at gaining access to the root surface to accomplish the removal of residual plaque/calculus with no active removal of bone and most often no resection of soft tissues. CS has been used as the control in the vast majority of trials evaluating regenerative techniques in intrabony defects. While the outcomes were generally inferior with respect to the regenerative procedure under study, signicant benecial eects of treatment were noted (Needleman et al. 2005). Nevertheless, the clinical ecacy of CS in treatment of intrabony defects may extensively vary (Tu et al. 2008). Possible reasons to explain this nding may be related to the technique such as ap design (i.e. papilla preservation), incision and suture. Despite the publication of several systematic reviews and meta-analysis evaluating regenerative therapy in the treatment of intrabony defects (Trombelli et al. 2002, Needleman et al. 2005, Esposito et al. 2009), a systematic assessment of the clinical performance of CS is still lacking. This information could be valuable for clinicians as CS is a technique with a favourable costbenet ratio commonly used in clinical practice and, furthermore, regenerative surgery may not be always indicated and/or the rst choice in the treatment of intrabony defects (Cortellini & Tonetti 2000). Therefore, objective of this study was to conduct a systematic review to investigate the clinical performance of conservative surgery in the treatment of intrabony defects caused by periodontal disease. Only control groups from randomized clinical trials (RCT) were included to (i) control the risk of biases, which may derive from case series even perspective, (ii) properly evaluate methodological quality of the information gathered and (iii) possibly explore the clinical performance of dierent ap designs.
Materials and Methods
Protocol development and eligibility criteria

ogy, the Journal of Periodontal Research and the Journal of Clinical Periodontology up to April 2011 and bibliographies of all retrieved papers and review articles.
Study selection and data collection

We conducted a search on electronic databases up to and including April 2011. The search was applied to the Cochrane Oral Health Group specialist trials, MEDLINE and EMBASE. The strategy used was a combination of MeSH terms and free text words:

Intervention: (surgical aps [mesh] OR periodontal pocket surgery [mesh] OR access [txt words] OR open [txt words] OR widman [txt words] OR papilla preservation [txt words] OR modied [txt words] OR simplied [txt words]); AND Disease: (intra bony defect* [txt words] OR intrabony defect* [txt words] OR infra bony defect* [txt words] OR infrabony defect* [txt words] OR infra-bony defect* [txt words] OR intrabony defect* [txt words] OR intra osseous [txt words] OR intraosseous [txt words] OR intraosseous [txt words]); AND Study design: (longitudinal study [mesh] OR randomised controlled study [mesh] OR comparative study [mesh] OR clinical trial [mesh]).

Eligibility assessment was performed through titles and abstract analysis and full text analysis. Titles and abstracts of the search results were initially screened by the two reviewers (S. C. and S.G.), for possible inclusion in the review. Reviewers were calibrated for study screening against another reviewer (F.G.) with experience in conducting systematic reviews. Each round of calibration consisted of a duplicate, independent validity assessment of 20 titles and abstracts from the search. After two rounds of calibration, a consistent level of agreement was found (unweighted k scores from rst to third exercise: 0.9, 1 and 1). To avoid excluding potentially relevant articles, abstracts providing an unclear result were included in the full text analysis. The full text of all studies of possible relevance was then obtained for independent assessment by two reviewers (F. G. and S.C.) against the stated inclusion criteria. Disagreement was checked by an independent reviewer (F.C.) and solved through discussion. The two reviewers conducted all quality assessments independently. Data of the included articles were extrapolated through an ad hoc extraction sheet. The extraction sheet, previously tested on possible included studies, was divided into two sections. In the rst section information such as baseline characteristics of the defect, length of follow-up, type of surgical intervention, tooth survival and surrogate parameters were collected. The second section focused on the quality of the study. Uncertainties on the quality assessment section were solved contacting the authors.
Outcome measures

A detailed protocol was designed according to the PRISMA (Preferred

Hand searching was also performed on Journal of Periodontol-

Primary outcome measures considered were tooth survival, CAL gain, PPD reduction and REC increase. Secondary information on both clinical and radiological bone gain was also collected. Tooth survival was dened as
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Access aps in intrabony defects

the percentage of retained teeth. When percentage was not provided, calculations were performed based on the raw data reported in the paper. CAL gain, PPD reduction and REC increase had to be expressed as the average dierence baseline/follow-up of the treated sites in millimetres. The reviewers did not make any additional calculations on CAL gain, PPD reduction and REC increase. Thus, studies not reporting dierences between baseline and follow-up examinations were excluded unless data of each patient was provided. In the latter case, average dierence was calculated by the authors. Hard tissue measurements were also evaluated as clinical and radiological bone gain. Clinical bone gain was considered as the dierence between baseline and follow-ups of the distance cement enamel junction bottom of the defect (CEJ-BD) when re-entry measurement was performed. Radiographic bone gain was the dierence between baseline and follow-ups of the distance of radiological CEJ-BD.
Risk of bias in individual studies

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Risk of bias was evaluated through quality analysis. Two reviewers (F.G and S.C) evaluated through some methodological criteria. Quality analysis of Randomized Clinical Trial (RCT) was performed according to the Cochrane Reviewers Handbook (Higgins & Green 2009). Briey included articles were evaluated through four methodological RCT aspects: (i) sequence generation, (ii) allocation concealment, (iii) blinding of personnel and outcome assessors and (iv) handling of incomplete outcome data. The four phases of the trial were deemed as adequate, inadequate or unclear (Higgins et al. 2009). Unclear ndings were considered when the included article did not or poorly address the four methodological issues and were solved through direct contact to the authors. To be included in the metaanalysis, articles had to be considered adequate in all four aspects.
Summary measures and synthesis of the results

and radiographic intrabony component were summarized as weighted mean dierences (WMD) and 95% condence interval (CI). Characteristics of the included subjects in terms of full-mouth plaque and bleeding scores (FMPS and FMBS respectively) and percentage of smokers were expressed as median of the percentages and inter-quartile range (IQ). Clinical performance in terms of overall tooth survival was summarized as median of the percentages and IQ. Moreover on CAL gain, PPD reduction, REC increase, radiological and clinical bone gain, a weighted treatment eect (preoperative-postoperative) was calculated and the results were expressed as WMD and 95% CI for continuous outcomes using both xed and random models. Mean dierences and standard errors were entered for each study to combine parallel group and intra-individual (split-mouth) studies (Needleman et al. 2005). CAL gain and PPD reduction were also summarized as percentage changes according to baseline values. These analyses were performed with Comprehensive Meta Analysis V2 software (Biostat, Englewood, NJ, USA). Data were collected in evidence tables and results of the meta-analysis were summarized with Forest plots. Data were considered short-term when follow-up did not extend for more than 12 months, whereas data were considered as medium-term when follow-up was of at least 24 months.
Risk of bias across studies

1974) were grouped together as aps with no clear attempt to anatomically conserve the inter-dental soft tissue. Modied papilla preservation technique (MPPT) (Cortellini et al. 1995b) and simplied papilla preservation ap (SPPF) (Cortellini et al. 1999) were grouped together as both often utilized within the same trials. Other aps considered were papilla preservation ap (PPF) (Takei et al. 1985), microsurgical periostealap variation of papilla preservation aps (PPPF) (Wachtel et al. 2003, Fickl et al. 2009, Stein et al. 2009) and modied minimally invasive surgical technique (M-MIST) (Cortellini & Tonetti 2011).
Results
Study selection

A total of 563 studies were identied for inclusion in the review. The electronic search determined a total of 508 articles. Hand searching identied a further 55 articles for the full text analysis (Fig. 1). Screening of titles and abstracts led to rejection of 456 articles and thus the full text of the remaining 107 articles was then obtained. After full-text analysis and the exclusion of further 35 articles (reasons for exclusion and list of excluded articles are depicted in Appendix S1). The full text of the remaining 72 articles was analysed for methodological quality and availability of data for meta-analysis (Appendix S2 reports excluded articles after methodological appraisal). Lastly, 30 articles met the criteria for inclusion in this meta-analysis.
Study characteristics

Heterogeneity between the studies was tested and evaluated through Q and I2 test. A p value of Q statistic < 0.1 was dened as an indicator of heterogeneity and data were considered heterogeneous for I2 value higher than 40%.
Additional analysis

Baseline defect characteristics in terms of CAL, PPD, REC, CEJ-BD, clinical

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Subgroup analysis, according to the type of ap used, was performed on baseline characteristics of the defects/subjects involved and shortterm WMD of CAL gain, PPD reduction and REC increase. Open ap debridment (OFD) (Kirkland 1931) and modied Widman ap (MWF) (Ramfjord & Nissle

Characteristics of the included studies are depicted in the Table 1. The pool of included material consisted of 30 articles representing 27 clinical trials. Sixteen trials were of parallel group design, the remaining 11 were split mouth. The number of subjects included in the overall analysis was 647 after adjustment for companion papers. Of the included articles, 25 reported 12-month data only, one reported both 12 months and longer follow-up (Francetti et al. 2004) and the remaining four reported followup of at least 36 months (Heijl et al. 1997, Sculean et al. 2005, 2007, 2008).

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Tooth survival At 12 months, there were four teeth lost out of 249 documented teeth (tooth survival 98.92%; IQ 96.77 100%). Reasons for tooth loss did not seem related to recurrence of periodontal disease. One tooth was lost for trauma and another one due to excessive mobility (Tonetti et al. 2004), one for reasons related to treatment plan (Zybutz et al. 2000) and one tooth loss was not specied (Mora et al. 1996). Longer follow-ups of at least 24 months showed one tooth lost on a total of 143 (98.99%; IQ 96.97 100%). Reasons for tooth loss were related to prosthodontic treatment plan (Heijl et al. 1997). CAL gain Forrest plots of the CAL gain after surgical intervention are depicted in Fig. 2. Information on CAL gain was obtained from 24 studies with 12 months of follow-up and four studies with longer follow up. CAL gain at 12 months was 1.65 mm (95% CI:1.36, 1.94; p < 0.0001) and 1.97 mm (95% CI: 1.13, 2.81; p < 0.0001) with follow-up of at least 24 months. Overall, proportion of CAL gain after conservative surgery was 21.95% (QI: 13.98 29.92%).
Results of individual studies and synthesis of results

Fig. 1. Flow of studies during review.

Risk of bias within studies

PPD reduction Forest plots of the PPD reduction after surgical intervention are depicted in Fig. 3. Twenty-two studies contributed to PPD reduction calculation at 12 months and four studies for longer follow up. PPD reduction at 12 months was 2.85 mm (95% CI: 2.47, 3.22; p < 0.0001) and 2.77 mm (95% CI: 1.59, 3.94; p < 0.0001) with longer follow-up. Percentage of PPD reduction after conservative surgery was 41.63%% (QI: 32.9150.33%). Residual PPD was 4.18 mm (95% CI: 3.71, 4.64) after 12 months and 5.06 mm (95% CI: 3.75, 6.36) at longer follow-ups. REC increase Forest plots of the REC increase after surgical intervention are depicted in Fig. 4. Eighteen studies contributed to REC increase at 12 months and two for longer follow-up. REC increase at 12 months was 1.15 mm (95% CI: 0.88, 1.42;
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Adequate methods of sequence generation, allocation concealment, blinding of personnel and outcome assessors and management of incomplete outcome data were reported in nine articles (Heijl et al. 1997, Okuda et al. 2000, Zybutz et al. 2000, Sculean et al. 2001, 2004, 2008, Francetti et al. 2004, Vouros et al. 2004, Kasaj et al. 2008). Unclear methods, solved through author contact, were identied in 21 articles. The reasons and the clarications obtained by the authors are reported in Appendix S3. Inadequate methods of study design were noted in eight articles (Masters et al. 1996, Cortellini et al. 1998, 2001, Tonetti et al. 1998, Silvestri et al. 2000, Minenna et al. 2005, Nickles et al. 2009, Rajesh et al. 2009), two of which were gathered directly from the article (Minenna et al. 2005, Rajesh et al. 2009).

Baseline characteristics of the included defects and subjects Baseline CAL was 8.75 mm (95% CI: 8.11, 9.39) and the average CAL baseline loss of the treated defect was deeper than 7 mm in the 90% of the included articles. PPD was 6.74 mm (95% CI: 6.43, 7.05), REC was 1.12 mm (95% CI: 0.58, 1.65), CEJBD was 10.87 mm (95% CI: 9.99, 11.75), the clinical intrabony component was 4.53 mm (95% CI: 4.03, 5.03) and radiological intrabony depth was 3.78 mm (95%: CI: 3.47, 4.09). At baseline FMPS, FMBS were 12.20% (QI: 9.5014.9%) and 10.55% (QI: 8.4212.67%) respectively. Smoking habits were investigated only in a fraction of the included studies and often no clear or consistent information was reported, thus it was not possible to collect meaningful information on this matter.

Access aps in intrabony defects

Table 1. Characteristics of the included studies Study Cortellini & Tonetti 2011 Methods Parallel group 12 months Control group participants 15 individuals 6 females 15 defects Average CAL 9.6 2 mm 19 individuals 13 females 35 defects Average CAL NR 15 individuals 15 defects Average CAL 7.7 0.9 mm 13 individuals 13 defects Average CAL 8.2 1.2 mm 9 individuals 9 defects Average CAL 10.4 1.3 mm 9 individuals 9 defects Average CAL 10.6 1.4 18 individuals 8 females 18 defects Average CAL 7.28 1.71 mm 70 individuals 87 defects Average CAL 7.98 2.07 mm 16 individuals 16 defects Average CAL 9.6 1.3 mm 12 individuals 12 defects Average CAL 8.29 1.60 mm 10 individuals 10 defects Average CAL 9.7 0.8 mm 62 individuals 62 defects Average CAL 9.9 2.3 mm 12 individuals 12 defects Average CAL 8.52 0.97 mm 14 individuals 14 defects Average CAL 10.5 1.5 mm 11 individuals 8 female 26 defects Average CAL 7.2 1.4 mm Interventions 1. M-MIST 2. EMD 3. EMD + Graft 1. SPPF 2. Emdogain Outcomes PPD, CAL, REC, Rx bone gain Tooth loss 0

149

Site and funding Private practice, self-funded

Fickl et al. 2009

Split-mouth group 12 months

PPD, CAL, REC, Rx bone gain

Private practice, self-funded

Stein et al. 2009

Parallel group 12 months

1. SPPF 2. Biomaterial Graft 3. Bone Graft 1. OFD 2. Biomaterial Graft

PPD, CAL, REC

NR

University, industry funded

Kasaj et al. 2008

Parallel group 12 months

PPD, CAL, REC

NR

University, funding NR

Sculean et al. 2008,*

Parallel group 120 months

Sculean et al. 2007,*

Parallel group 60 months

1. 2. 3. 4. 1. 2.

OFD EMD GTR EMD + GTR OFD GTR + Graft

PPD, CAL, REC

University, self-funded

PPD, CAL, REC

University, funding NR

Aimetti et al. 2005

Split mouth group 12 months

1. MPPF& OFD 2. GTR

PPD, CAL, REC, clinical bone gain

University, funding NR

Francetti et al. 2005

Parallel group 24 months

1. SPPF 2. EMD

PPD, CAL, Rx bone gain

University/Private Practice, funding NR

Sculean et al. 2005

Parallel group 12 months

1. SPTF/MPPF 2. GTR + Graft 1. SPPF 2. EMD

PPD, CAL, REC

University, funding NR

Francetti et al. 2004

Parallel group 24 months

PPD, CAL, Rx bone gain

University, funding NR

Sculean et al. 2004,*

Parallel group 60 months

Tonetti et al. 2004

Parallel group 12 months

1. 2. 3. 4. 1. 2.

OFD EMD GTR EMD + GTR MPPF GTR

PPD, CAL, REC

University, funding NR

PPD, CAL, REC, Rx bone gain

Private practice, self/industry

Vouros et al. 2004

Parallel group 12 months

1. OFD 2. GTR + Graft 3. GTR + Graft 1. OFD 2. GTR + Graft 1. MPPF 2. EMD

PPD, CAL, REC

NR

University, funding NR

Sculean et al. 2003,*

Parallel group 12 months

PPD, CAL, REC

University, funding NR

Wachtel et al. 2003

Split mouth group 12 months

PPD, CAL, REC

NR

University, funding NR

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Table 1. (continued)

Study Tonetti et al. 2002

Methods Parallel group 12 months

Control group participants 83 individuals 83 defects Average CAL 9.1 2.0 mm 30 individuals 30 defects Average CAL 10 1.2 mm 14 individuals 14 defects Average CAL 10.1 1.6 mm 16 individuals 8 females 18 defects Average CAL 6.83 1.2 mm 16 individuals 8 female 21 defects Average CAL 9.3 2.1 mm 29 individuals 16 females 29 defects Average CAL (1) 7.2 2.2 mm Average CAL (2) 7.8 1.9 mm 18 individuals 18 defects Average CAL 10.9 2.4 mm 33 individuals, 34 defects Average CAL 9.3 2.0 mm 22 individuals 12 female 22 defects Average CAL 12.2 2.30 mm 12 individuals 8 female 12 defects Average CAL 10.3 1.9 mm 15 individuals 15 defects Average CAL 9.5 2.7 10 individuals 10 defects 6 females Average CAL of 9.2 3.0 mm 15 individuals 8 females 15 defects Average CAL of 9.5 2.7 mm

Interventions 1. SPPF/MPPF 2. EMD

Outcomes PPD, CAL, REC

Tooth loss NR

Site and funding University/Private practice, private funded University, funding NR

Zucchelli et al. 2002

Parallel group 12 months

1. SPPF 2. EMD 3. GTR 1. 2. 3. 4. 1. 2. OFD EMD GTR GTR + EMD OFD EMD

PPD, CAL

Sculean et al. 2001,*

Parallel group 12 months

PPD, CAL, REC

University, funding NR

Okuda et al. 2000

Splith mouth

PPD, CAL, REC

University, funding NR

Ratka-Kruger et al. 2000

Split mouth & parallel group 12 months

1. OFD 2. GTR

PPD, CAL, REC, RX bone gain

University, funding NR

Zybutz et al. 2000

Split mouth & parallel group 12 months

1. 2. 3. 4.

OFD GTR OFD GTR

PPD, CAL, REC, RX bone gain

University, industry/ public funding NR

Mayeld et al.1998

Parallel group 12 months

1. OFD 2. GTR

PPD, CAL, REC, Clinical bone gain, Rx bone gain CAL, PPD, Rx bone gain

University, self/ industry funded

Heijl et al. 1997

Split mouth 36 months

1. OFD 2. EMD

University, funding NR

Zamet et al. 1997

Split mouth 12 month

1. OFD 2. Graft

PPD, CAL

University, industry funded

Cortellini et al. 1996

Parallel group 12 months

1.OFD 2. GTR 3. GTR

CAL

Private Practice, private/self funded

Tonetti et al. 1996

Parallel group 12 months

1. OFD 2. GTR 3. GTR 1. OFD 2. GTR

PPD, CAL

University, private/ self funded

Mora et al. 1996

Split mouth 12 months

PPD, CAL, REC, Clinical bone gain

University, funding NR

Cortellini et al. 1995a

Parallel group 12 months

1. OFD 2. GTR 3. GTR

CAL

Private Practice, private funded

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Table 1. (continued)

151

Study Mora & Ouhayoun 1995

Methods Split mouth 12 months

Control group participants 10 individuals 10 defects 5 female Average CAL of 7.3 1.5 mm 13 individuals 8 females 42 defects

Interventions 1. PPF 2. Graft 3. Graft

Outcomes PPD, CAL, REC, Clinical bone gain

Tooth loss 0

Site and funding University, funding NR

Yukna et al. 1985

Split-mouth 12 months

1. OFD 2. Graft

PPD, CAL, REC, Rx bone gain

University, funding NR

*Companion papers. CAL, clinical attachment level; PPD, pocket probing depth; REC, recession; NR, not reported; GTR, guided tissue regeneration; EMD, emdogain; SPPF, simplied papilla preservation ap; M-MIST, modied-minimally invasive surgical technique; MPPF, modied papilla preservation ap; PPF, papilla preservation ap; OFD, open ap debridment.

CAL gain WMD was 1.57 mm (95% CI: 1.25, 1.89; p < 0.0001) (Fig. 6), PPD reduction 2.77 mm (95% CI: 2.33, 3.21; p < 0.0001) and REC increase was 1.35 mm (95% CI: 1.01, 1.29; p < 0.0001). Percentage of CAL gain and PPD reduction were 20.00% (QI: 14.5025.49%) and 42.85% (QI: 40.0745.63%) respectively. Residual PPD was 4.40 mm (95% CI: 3.74, 5.05). PPF
(a)

Papilla preservation ap was used in one trial only (Mora & Ouhayoun 1995). Baseline defect and subjects characteristics indicated a CAL of 9.5 mm (SD 2.7), PPD 7.3 mm (SD 1.5). CAL gain was 1.3 mm (1.5 SD), PPD reduction 2.0 mm (1.3 SD) and REC 0.7 mm (0.7 SD). Residual PPD was 4.25 mm (DS 1.3). MPPT and SPPF Defects treated with MPPT and SPPF showed a baseline CAL of 9.40 mm (95% CI: 7.81, 10.98) and a PPD of 8.02 mm (95% CI: 6.83, 9.21). Baseline FMPS score was 12.2% (QI: 11.912.5%) and FMBS was 11.33% (QI: 9.9312.73%). CAL gain was 2.48 mm (95% CI: 1.44, 3.52; p < 0.0001). PPD reduction WMD was 3.59 mm (95% CI: 2.33, 4.85; p < 0.0001) and REC increase was 1.31 mm (95% CI: 0.20, 2.43; p < 0.0001). Percentage of CAL gain and PPD reduction were 26.73% (QI: 25.0328%) and 37.57% (QI:33.4541.70%) respectively. Residual PPD was 4.35 mm (95% CI: 2.91, 5.79).

(b)

Fig. 2. Forest plot from xed eects of meta-analysis evaluating the dierence in CAL gain (in mm) 12 months (a) and longer term (b) after conservative surgical treatment (weight mean dierence, 95% CI). NR, not reported; SD, standard deviation.

p < 0.0001) and 1.78 mm (95% CI: 1.00, 2.55; p < 0.0001) with longer follow-up. Radiological and clinical bone gain Forest plots of the clinical and radiological bone gain after surgical intervention are depicted in Fig. 5. Clinical and radiological bone gains were gathered from 4 to 7 studies respectively. Clinical bone gain at 12 months was 1.04 mm (95% CI: 0.64, 2.16; p < 0.001). Radiological bone gain at 12 months was 0.95 mm (95% CI: 0.62, 1.28; p = 0.066).
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Risk of bias across studies

Data presented did not show a signicant level of heterogeneity (I2 = 0.0%; p > 0.5).
Additional analysis

OFD and MWF At baseline, defects treated with OFD and MWF showed a CAL of 8.91 mm (95% CI: 8.03, 9.80), a PPD of 6.56 mm (CI 95%: 6.22, 6.91). FMPS and FMBS were 13.75% (QI: 11.9515.55%) and 12.2% (QI: 10.913.5%) respectively.

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was provided. In total, (Fickl et al. 2009, Stein et al. 2009) CAL gain was 1.62 mm (95% CI: 0.41, 2.83) PPD reduction was 2.69 mm (95% CI: 1.35, 4.03) and REC increase was 1.03 mm (95% CI: 0.07, 2.00). The proportions of CAL gain and PPD reduction were 20.77% and 39.43% respectively. Residual PPD was 4.3 mm (DS 0.8). M-MIST M-MIST was used in one trial only (Cortellini & Tonetti 2011). Baseline defects characteristics indicated a CAL of 9.6 mm (SD 2.0), PPD 7.5 mm (SD 1.6) and REC 2.1 (SD 1.4). FMPS and FMBS were 13.6% (SD 4.9) and 10.3% (SD 4.4) respectively. CAL gain was 4.1 mm (SD 1.4), PPD reduction 4.4 mm (SD 1.6) and a slight decrease of recession of 0.3 mm (SD0.6) were noted postoperatively. The proportions of CAL gain and PPD reduction were 42.70% and 58.66% respectively. Residual PPD was 3.1 mm (DS 0.6).
Discussion

(a)

(b)

Fig. 3. Forest plot from xed eects of meta-analysis evaluating the dierence in PPD reduction (in mm) 12 months (a) and longer term (b) after conservative surgical treatment (weight mean dierence, 95% CI). NR, not reported; SD, standard deviation.

(a)

(b)

Fig. 4. Forest plot from xed eects of meta-analysis evaluating the dierence in REC increase (in mm) 12 months (a) and longer term (b) after conservative surgical treatment (weight mean dierence, 95% CI). NR, not reported; SD, standard deviation.

PPPF Baseline values for PPPF group were available only for one study (Stein

et al. 2009). CAL was 7.7 mm (SD 0.9), PPD 7.1 mm (SD 0.8), no information on FMPS and FMBS

This systematic review was designed to evaluate the clinical performance, in terms of both tooth survival and clinical periodontal surrogate outcomes, of conservative surgical treatment of periodontal intrabony defect. Defects were characterized by an average intrabony component of 4.53 mm, 8.75 mm of CAL and 6.74 mm of pocketing. Overall, the evidence gathered suggests that, in these defects, conservative surgical treatment is associated with high levels of short-term (12 month) tooth retention. Evidence for longer term follow-up is limited to a restricted number of studies. Surrogate outcomes clinical attachment level and pocket depth improved. The magnitude of the improvements, however, was limited. A sub-analysis, assessing surrogate outcomes as a function of ap design, revealed that better outcomes seemed to be associated with papilla-preservation aps. In our meta-analysis, only intrabony defects treated conservatively in randomized clinical trials were included. However, as it is not objective of this review to compare conservative surgical treatment versus other treatments such as regenerative, other type of study design
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(a)

(b)

Fig. 5. Forest plot from xed eects of meta-analysis evaluating the dierence in clinical bone gain (a) and radiological bone gain (b)(in mm) 12 months after conservative surgical treatment (weight mean dierence, 95% CI). NR, not reported; SD, standard deviation.

(a)

(b)

(c)

Fig. 6. Forest plot from xed eects of meta-analysis evaluating the dierence in CAL gain (in mm) 12 months after conservative surgical treatment with OFD (a), papilla preservation ap (b), periosteal papilla preservation ap (c) (weight mean dierence, 95% CI). NR, not reported; SD, standard deviation.
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might have been included. Therefore, possible information gathered through cohort studies and non-randomized clinical trials might have been added. Nevertheless, to reduce the possible impact of biases, the authors decided to include only RCT which may ultimately be more easily controlled and checked in every study phase (Moher et al. 2010, Schulz et al. 2010). Moreover, some articles were not included in the nal selection as authors could not be contacted or did not provide or provided only partially data regarding the quality evaluation. These results are signicant in three directions: (i) the application of conservative surgery for the management and maintainability of deep intrabony defects; (ii) the biology of wound healing and the evidence supporting the choice of a specic ap design; and (iii) the design of future trials for the treatment of intrabony defects. The use of access ap surgery is a recognized standard to manage residual pockets after cause-related therapy. Recent systematic reviews have shown that it results in shallower pockets and a modest increase in clinical attachment levels (Trombelli et al. 2002, Needleman et al. 2005, Esposito et al. 2009). In exploratory analyses, benets seem to increase as residual pocket depths increase. As deeper residual pockets are frequently associated with intrabony defects, this systematic review assesses the applicability of access ap approaches to these challenging defects. Indeed, the included defect population represents areas with deep intrabony defects and deep residual pockets. In this context, the improvements in surrogate outcomes are signicant, as they are observed in studies at low risk of bias and thus at low risk of overestimation of the treatment eect, and in challenging defects where the application of osseous resective approaches is limited by the compromise of the support of adjacent teeth. Indeed, the only clinical alternative is represented by regenerative surgery. Nevertheless, the costs of regenerative surgery are signicant. Moreover, in some highrisk groups, such as smokers or subjects with incomplete control of the local etiological factors, the adjunctive benet of periodontal regeneration may be limited (Tonetti

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obtained after papilla preservation aps, greater amounts of clinical attachment level gains and lower amounts of recession of the gingival margin are observed. With the caveat that no study has directly compared the two surgical approaches, these healing patterns are interesting, as they suggest that healing of a ap that provides primary intention healing and greater wound stability may result in better outcomes. Several lines of preclinical research support this hypothesis. Indirect support comes from the ndings of a systematic review assessing the temporal trend of healing of surgical aps used for intrabony defects where a consistent increase of access ap performance was noted over a 15-year period (Tu et al. 2008). This temporal trend can in fact be interpreted as the result of the more widespread usage of papilla preservation aps in more recent years. Most probably, the faster recovery of vascular stability of the ap within the papillary area ensured by preservation aps (Retzepi et al. 2007) determines a higher stability of the blood clot in the inter-proximal area and therefore a more favourable healing of the intrabony defect. Interestingly, recent evidence suggests that new type of papilla preservation aps alone, in defects limited to the inter-proximal area, determines as much clinical and radiographic healing as regenerative treatment (Trombelli et al. 2010, Cortellini & Tonetti 2011). This further testies the potentialities of this particular technique. Randomized controlled trials comparing these two modalities are urgently required to determine if the standard of conservative surgery requires the adoption of a papilla preservation design. With respect to the design of future trials for the (regenerative) management of intrabony defects, the results of this systematic review and meta-analysis raise the doubt that even in the absence of direct comparisons the control (vehicle) arm of RCT needs to incorporate a papilla preservation ap as the standard surgical approach. The rationale is manifold: (i) for a regenerative material to be eective, its containment under the ap is paramount. As this can only be predictably achieved with a papilla preservation design (Takei et al. 1985), the same surgical design needs to be applied to the controls. (ii) Preclinical studies have indicated that wound and clot stability are key to successful regenerative treatment (Wikesjo et al. 1991), wound failure has been associated with incomplete clinical outcomes (Tonetti et al. 1993, Falk et al. 1997, Sanz et al. 2004) and papilla preservation aps have been associated with low rates of wound failure during the initial, critical weeks of healing (Cortellini & Tonetti 2001, 2007, 2009). Furthermore, (iii) the additional analyses of this systematic review suggest better outcomes with papilla preservation aps. It can be argued that, even in the absence of direct evidence, and given the lack of adverse events reported with papilla preservation aps, they may represent the best available technique to gain surgical access to the defects. In conclusion, treatment of intrabony defect with CS appears to be associated with improvement of periodontal clinical parameters and high tooth retention. The clinical performance may vary signicantly according to the type of surgical ap adopted. In terms of clinical research, long-term studies evaluating tooth retention and clinical trials comparing dierent surgical techniques are advocated. Furthermore, on the basis of our ndings, the use of papilla preservation ap as the standard surgical approach in RCT is strongly encouraged. Lastly, clinicians should bear in mind that in intrabony defects, conservative surgery may represent a viable therapeutic option when regenerative treatment is not feasible.
References
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et al. 1995, Heitz-Mayeld et al. 2006) and therefore the control treatment, i.e. conservative surgery, may present an excellent costbenet ratio (Listl et al. 2010). On the other hand, the limited information available (Renvert et al. 1985) indicates that conservative surgery provides an additional benet compared with closed ap root debridement alone, despite the potential benets of scaling and root-planing alone highlighted in a recent retrospective report (Nibali et al. 2011). This benet in surrogate outcomes of conservative surgery is conrmed by high rates of 12-month tooth retention. Longer term, however, the available evidence is modest both in terms of number of subjects and in terms of length of follow-up. Indeed, as it is expected that in a substantial proportion of cases the residual pocket depth at the 12-month followup exceeded the 45 mm range, it is possible that, as suggested by Matuliene et al. (2008), recurrence of periodontitis and eventually tooth loss may happen in an undetermined proportion of cases after an adequate follow-up period. High-quality studies with long-term follow-up are needed to better understand the performance of conservative surgery in intrabony defects. Cigarette smoking (Mayeld et al. 1998) has been indicated as a negative prognostic factor of conservative surgical treatment; nevertheless, smoking habits were investigated only in a limited fraction of the included studies and the inconsistent denition of smokers and the great variability of inclusion/exclusion criteria on this matter nullied a possible sub-group analysis. A second aspect worthy of attention is the healing mode associated with the clinical outcomes: with conventional conservative surgical approaches (i.e. access aps without preservation of the inter-dental tissues), lack of primary wound closure and the consequent lack of clot stability has been associated with a histological healing characterized by repair. From a clinical standpoint, the clinical improvement is the result of a less apical penetration of the probe tip combined with a recession of the gingival margin. Interestingly, when the results of access ap surgery are compared with those

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Supporting Information

Additional Supporting Information may be found in the online version of this article: Appendix S1. Characteristics of the excluded articles after full text analysis. Appendix S2. Characteristics of the excluded full text after methodological appraisal. Appendix S3. Methodological issues claried after author contacting. Please note: Wiley-Blackwell are not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article.
Address: F. Graziani Department of Surgery, Unit of Dentistry and Oral Surgery University of Pisa Pisa, Italy E-mail: lippo.graziani@med.unipi.it

Clinical relevance

Scientic rationale for the study: To investigate and assess the clinical performance of conservative surgical aps in the treatment of intrabony defect.

Principal ndings: Conservative surgery is associated with high tooth survival 12 months after surgery and medium-term data reports stable outcomes. Papilla preservation aps seem to be associated with better clinical outcomes.

Practical implications: Clinicians should bear in mind that when regenerative treatment is not feasible, conservative surgical treatment especially with papilla preservation aps may be a valid therapeutic alternative.
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