Regenerative Approaches in the Treatment of Furcation Lesions are Predictable in Class II Maxillary Facial or Interproximal and Mandibular Facial or Lingual Class II Furcation Defects

REVIEW ANALYSIS & EVALUATION ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION Periodontal regeneration – furcation defects: a systematic review from the AAP regeneration workshop. Avila-Ortiz G, De Buitrago JG, Reddy MS. J Periodontol. 2015;86(2 Suppl):S108-30.

Regenerative Approaches in the Treatment of Furcation Lesions are Predictable in Class II Maxillary Facial or Interproximal and Mandibular Facial or Lingual Class II Furcation Defects

REVIEWERS Fernanda Vieira Ribeiro, DDS, MS, PhD, Professor, Marcio Zaffalon Casati, DDS, MS, PhD, Professor

PURPOSE/QUESTION The authors conducted a systematic review of clinical studies on the effectiveness of various regenerative approaches for the treatment of furcation defects in specific clinical scenarios compared with conventional surgical therapy.

SOURCE OF FUNDING As described by the authors, Dr. Avila-Ortiz has received research funding from Osteogenics Biomedical (Lubbock, Texas), Geistlich Pharma (Wolhusen, Switzerland), DENTSPLY (York, Pennsylvania), and BioHorizons (Birmingham, Alabama) and lecture honoraria from Laboratorios INIBSA (Barcelona, Spain). Dr. Reddy has received grant support and other funding through his institution, the University of Alabama at Birmingham; from BioDLogics (Memphis, Tennessee), Biomet 3i (Palm Beach Gardens, Florida), Procter & Gamble (Cincinnati, Ohio), Institute Straumann (Basel, Switzerland), Sunstar Americas (Chicago, Illinois), Zimmer Dental (Carlsbad, California), BioHorizons, National Institutes of Health, and National Institute of Dental and Craniofacial Research. Dr. De Buitrago reports no conflicts of interest related to this review. The 2014 Regeneration Workshop was hosted by the American Academy of Periodontology (AAP) and supported in part by the AAP Foundation, Geistlich Pharma North America, ColgatePalmolive, and the Osteology Foundation.

TYPE OF STUDY/DESIGN Systematic review

LEVEL OF EVIDENCE Level 2: Limited quality, patient-oriented evidence

STRENGTH OF RECOMMENDATION GRADE Grade B: Inconsistent or limited quality patientoriented evidence

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SUMMARY Selection Criteria This study comprises a systematic review of studies evaluating the effect of various well-recognized regenerative techniques for the management of furcation lesions in specific clinical scenarios compared with nonregenerative surgical therapy. The following clinical scenarios were evaluated: (1) maxillary molars with facial/interproximal Class I furcation defects; (2) mandibular molars with facial/lingual Class I furcation defects; (3) maxillary molars with facial/interproximal Class II furcation defects; (4) mandibular molars with facial/lingual Class II furcation defects; (5) maxillary molars with Class III furcation defects; (6) mandibular molars with Class III furcation defects; and (7) maxillary premolars with Class I, II, or III furcation defects. Two investigators reviewed four databases (MED LINE/PubMed, Scopus, Web of Knowledge, and the Cochrane Central Register of Controlled Trials) for human studies published in English, matching specific inclusion criteria (see below in Key Study Factor section). Initially 1500 entries were identified. The total number of articles selected after reviewing the titles and abstracts was 183, of which 150 were eligible after full-text review. A total of 24 clinical trials and 13 case series did not report clearly the clinical scenarios for the furcation defects. A total of 113 manuscripts were included in the systematic review (6 systematic reviews, 85 clinical trials, 14 case series, and 8 case reports).

Key Study Factor Articles reporting original studies (including, in a non-restrictive manner, human patient clinical trials, cohort studies, case series, and case reports) and systematic reviews on the topic of periodontal regenerative treatment in furcation defects were eligible. To be included, studies must have recruited patients aged >18 years who had at least one furcation defect treated with regenerative therapy. Indeed, eligible studies must report at least one outcome of interest (see below in Main Outcome Measure section). Studies that did not report the data separately and clearly for any of the previously mentioned clinical scenarios categorizing the furcation involvement were considered as ‘‘non-classifiable’’ and their data were not abstracted.

Main Outcome Measure The authors considered a variety of outcome measures, and not a main measure, to determine the effectiveness of regenerative approaches in furcation defects: (1) clinical parameters: closed measurements (vertical probing depth [VPD]/horizontal probing depth [HPD] reduction and vertical attachment level [VAL]/horizontal attachment level [HAL] gain) and open measurements (furcation defect fill/volume reduction, furcation closure rate on re-entry, and long-term tooth survival rate); (2)

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radiographic outcomes: furcation fill and changes in density; (3) histologic evaluation: evidence of periodontal regeneration and characteristics of different tissue compartments; (4) microbiologic analysis: reduction of specific bacterial species; and (5) patient-related outcomes: rate of complications, perceived benefit, and changes in quality of life.

Main Results Given the methodologic heterogeneity and the wide diversity of techniques and materials assessed in the selected studies, the conduction of a meta-analysis was not viable. A summary of the main data from previous systematic reviews and information related to the indication of regenerative therapeutic alternatives for the treatment of furcation lesions compared with non-regenerative surgical therapy was presented. In brief, the authors reported that the main findings from the six previously published systematic reviews were consistent in the conclusion that regenerative approaches are more effective than conventional surgical therapies in the treatment of furcation defects. When describing the available evidence from clinical studies, specific clinical scenarios were considered. Of the 85 clinical trials, 8 revealed outcomes after applying regenerative therapy on maxillary facial/interproximal Class II furcation, 68 on mandibular facial/lingual Class II furcation, 1 on maxillary Class III furcation, 9 on mandibular Class III furcation, and 1 on maxillary premolars presenting Class I and Class II furcation defects. Of the 14 selected case series, 2 described the treatment of maxillary facial/interproximal Class II furcation, 11 mandibular facial/lingual Class II furcation, and 2 mandibular Class III furcation involvement. Of the 8 case reports, 2 reported the use of regenerative therapies on maxillary facial/interproximal Class II furcation, 6 on mandibular facial/lingual Class II furcation, and 1 on mandibular Class III furcation lesions. None of the studies reported on the application of regenerative therapies in maxillary or mandibular Class I furcation defects in molars. In general, the selected literature pointed out that periodontal regeneration in furcation involvements is possible in specific clinical scenarios, mainly maxillary and mandibular Class II lesions.

Conclusions The authors concluded that the indication of regenerative therapeutic approaches for the management of furcation lesions is predictable in specific clinical scenarios, especially in maxillary facial or interproximal and mandibular facial or lingual Class II furcation defects.

COMMENTARY AND ANALYSIS Furcation involvements are commonly detected in individuals presenting with periodontitis, and longitudinal clin106

ical trials have shown that teeth with furcation lesions respond least favorably to periodontal therapy, being more susceptible to additional attachment loss.1,2 Regeneration is defined as the reconstitution of lost tissues, re-establishing the original architecture and function of the destroyed structures. The chief objective of regenerative periodontal therapeutic strategies is to reconstruct the anatomy and function of the periodontium damaged by periodontitis, including alveolar bone, root cementum, and functionally oriented periodontal ligament, especially in teeth with furcation involvements that are considered to be at greater risk of extraction compared with periodontal defects surrounding single-rooted teeth. The authors of this review sought to explore the available evidence regarding the effectiveness of regenerative procedures in treating furcation defects in specific clinical scenarios compared with conventional surgical therapy. Based on the available evidence, the authors of this systematic review pointed out, among other conclusions, that ‘‘Periodontal regeneration has been demonstrated histologically and clinically for the treatment of maxillary facial or interproximal and mandibular facial or lingual Class II furcation defects,’’ which is a plausible finding considering the presence of many studies showing mainly promising clinical, and less frequently histological outcomes, of regenerative strategies in this type of furcation defect, although conduction of a meta-analysis was not viable in the current review. In addition, the author’s conclusion also reported that ‘‘the clinical evidence supporting the indication of periodontal regenerative therapy in the treatment of mandibular Class III defects is limited to case reports’’ and that ‘‘regenerative therapy in maxillary molars presenting Class III defects and in maxillary premolars affected by Class II or III defects is not predictable based on current available evidence.’’ The authors also emphasized that ‘‘in Class I defects, regenerative therapy may be beneficial in certain clinical scenarios, although most of these defects may be successfully treated with non-regenerative therapy.’’ Some aspects should be addressed concerning this systematic review. First, as mentioned by the authors, the studies included in this systematic analysis presented noticeable methodologic heterogeneity (different study designs and varied outcome measurements). Indeed, the selected literature exhibited extensive diversity and combinations of techniques and of biomaterials applied. In addition, some of the studies analyzed in the systematic review presented relatively low sample size or they did not report a sample size calculation. All these aspects need to be rigorously observed when interpreting the results shown, as clearly highlighted in the study. A second point to be considered, especially when taking into account the effects of regenerative procedures, is that the only reliable method of determining periodontal regeneration is histology,3 although clinical and radiographic parameters are indispensable. September 2015

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Importantly, the success of periodontal therapeutic approaches has usually been validated with clinical parameters such as probing depth reduction, clinical attachment level gain, and radiographic bone fill. Nevertheless, the employment of these traditional outcome indicators does not reflect the real patient-reported outcomes, such as the consequences of periodontal treatment on patients’ daily routine. Thus, improvements in patientoriented outcomes, i.e., patients’ psychological wellbeing during and after the procedures, morbidity, satisfaction, and aesthetics perceptions, and impact on the quality of life after therapies are important aspects for consideration in clinical trials, since they are critical in fully evaluating the effectiveness of different therapies. Although the author’s efforts to conduct recommendations based on patient-oriented measures are evident, scarce information is available describing the effects of regenerative approaches in the patient centeredoutcomes, as reported in the review. Surrogate end points are the most used parameters evaluated in the existing literature on the topic of periodontal regeneration of furcation defects. Some limitations of knowledge were identified in the systematic review, as recognized by the authors, suggesting that the focus of additional research should be the conduction of randomized controlled clinical trials that compare conventional surgical interventions with innovative regenerative approaches that may surpass the limitations of techniques already known for the management of clinical conditions related to unpredictable results, such as Class III furcation defects. Taking into account all these factors, it was not possible to indicate definite and precise guidelines appropriate for clinical decision making related to the management of furcation defects, given their complex anatomy and variable morphology and location.

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In conclusion, considering that regenerative approaches for the maintenance of teeth presenting furcation involvements could improve their survival rate after a longer follow-up period, the findings of this systematic review confirm the need for expanding efforts to improve the knowledge in making good clinical decisions about regenerative interventions to the treatment of furcation defects, focusing especially on the patient-reported outcomes essential to clinical recommendations of evidence-based therapies and focusing attention to the development of new therapeutic approaches able to promote periodontal regeneration in furcations with challenging morphology.

REFERENCES 1. Tomasi C, Leyland AH, Wennstr€ om JL. Factors influencing the outcome of non-surgical periodontal treatment: a multilevel approach. J Clin Periodontol 2007;34(8):682-90. 2. Ekuni D, Yamamoto T, Takeuchi N. Retrospective study of teeth with a poor prognosis following non-surgical periodontal treatment. J Clin Periodontol 2009;36(4):343-8. 3. Reddy MS, Jeffcoat MK. Methods of assessing periodontal regeneration. Periodontol 2000 1999;19:87-103.

REVIEWERS Fernanda Vieira Ribeiro Dental Research Division, School of Dentistry, Paulista University, Av. Dr. Bacelar, 1212, 4o andar, Vila Clementino, S~ a o Paulo, S~ a o Paulo, Brazil, Tel./fax: þ55 (11) 5586 4000 [email protected] Marcio Zaffalon Casati Dental Research Division, School of Dentistry, Paulista University, Av. Dr. Bacelar, 1212, 4o andar, Vila Clementino, S~ a o Paulo, S~ a o Paulo, Brazil Department of Prosthodontics and Periodontics, School of Dentistry at Piracicaba, University of Campinas (UNICAMP), Piracicaba, S~ a o Paulo, Brazil

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