Volume 86 • Number 2 (Suppl.

Periodontal Regeneration – Furcation

Defects: A Systematic Review From
the AAP Regeneration Workshop
Gustavo Avila-Ortiz,* Juan G. De Buitrago,* and Michael S. Reddy†

Background: The aim of this review is to present the available evidence regarding the effectiveness of
different regenerative approaches for the treatment of furcation defects in specific clinical scenarios com-
pared with conventional surgical therapy to provide clinical guidelines for the therapeutic management of
furcation defects and to identify priorities for future research that may advance the understanding of peri-
odontal regenerative medicine.
Methods: A comprehensive search based on predetermined eligibility criteria was conducted to iden-
tify human original studies and systematic reviews on the topic of periodontal regeneration of furcation
defects. Two reviewers independently screened the title and abstract of the entries yielded from the initial
search. Subsequently, both reviewers read the full-text version of potentially eligible studies, made a final
article selection, and extracted the data of the selected studies considering specific clinical scenarios. The
clinical scenarios contemplated in this review included the following: 1) facial and interproximal Class I
defects in maxillary molars; 2) facial and lingual Class I defects in mandibular molars; 3) facial and in-
terproximal Class II furcation defects in maxillary molars; 4) facial and lingual Class II furcation defects
in mandibular molars; 5) Class III furcation defects in maxillary molars; 6) Class III furcation defects in
mandibular molars; and 7) Class I, II, or III furcation defects in maxillary premolars. Endpoints of interest
included different clinical, radiographic, microbiologic, histologic, and patient-reported outcomes.
Results: The initial search yielded a total of 1,500 entries. The final selection consisted of 150 articles,
of which six were systematic reviews, 109 were clinical trials, 27 were case series, and eight were case
reports. A summary of the main findings of previously published systematic reviews and the available ev-
idence relative to the indication of regenerative approaches for the treatment of furcation defects com-
pared with conventional surgical therapy are presented. Given the marked methodologic heterogeneity
and the wide variety of materials and techniques applied in the selected clinical trials, the conduction
of a meta-analysis was not viable.
Conclusions: On the basis of the reviewed evidence, the following conclusions can be drawn. 1) Peri-
odontal regeneration has been demonstrated histologically and clinically for the treatment of maxillary
facial or interproximal and mandibular facial or lingual Class II furcation defects. 2) Although periodontal re-
generation has been demonstrated histologically for the treatment of mandibular Class III defects, the evidence
is limited to one case report. 3) Evidence supporting regenerative therapy in maxillary Class III furcation de-
fects in maxillary molars is limited to clinical case reports. 4) In Class I furcation defects, regenerative therapy
may be beneficial in certain clinical scenarios, although most Class I furcation defects may be successfully
treated with non-regenerative therapy. 5) Future research efforts should be primarily directed toward the con-
duction of clinical trials to test novel regenerative approaches that place emphasis primarily on patient-
reported outcomes and also on histologic demonstration of periodontal regeneration. Investigators should
also focus on understanding the influence that local, systemic, and technical factors may have on the out-
comes of regenerative therapy in furcation defects. J Periodontol 2015;86(Suppl.):S108-S130.
KEY WORDS
Evidence-based dentistry; furcation defects; periodontal diseases; reconstructive surgical procedures;
regeneration.

* Department of Periodontics, University of Iowa, Iowa City, IA.

† Department of Periodontology, School of Dentistry, University of Alabama at Birmingham, Birmingham, AL.

See related practical applications paper in Clinical Advances in Periodontics (February 2015, Vol. 5, No. 1) at www.clinicalperio.org.

doi: 10.1902/jop.2015.130677

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J Periodontol • February 2015 (Suppl.)
T
he furca can be defined as the anatomic area of
a multirooted tooth in which the roots diverge.
Furcation invasion or involvement is the result
of ‘‘pathologic resorption of the supporting alveolar
bone within a furcation,’’ typically derived from the
progression of chronic or aggressive periodontitis.1
Although teeth presenting furcation involvement can
be maintained for years under the appropriate con-
ditions of care,2 the treatment of furcation defects
represents a clinical challenge given their intricate
anatomy and variable morphology,3-7 which com-
plicates the access for proper hygiene, debridement,8
and maintenance.9,10 The degree of furcation in-
volvement is commonly used as a clinical indicator to
qualify the severity of existing periodontal breakdown
and to determine the likelihood of future attachment
and tooth loss in multirooted teeth.11,12 In a classic
landmark study, Hirschfeld and Wasserman13 ob-
served that teeth with furcation involvement exhibited
a higher rate of tooth loss (31%) compared with teeth
that did not present furcation defects (7%) over a pe-
riod of ‡15 years. Furthermore, several studies have
demonstrated that, in multirooted teeth, sites pre-
senting furcation defects respond less favorably to
non-surgical therapy compared with sites that do not
have furcation involvement.14,15 The presence of
proximal deep furcation defects may not only ad-
versely affect the response to therapy of an affected
tooth but also the prognosis of adjacent teeth.16
WHAT IS THE SIGNIFICANCE OF THIS TOPIC?
A common dilemma faced by clinicians in daily clinical
practice is whether to recommend the treatment of
a furcation defect, with the ultimate goal of preserving
the affected tooth, or to indicate tooth extraction and its
replacement with a prosthetic option (e.g., removable,
tooth supported, or implant supported). Interestingly,
according to Huynh-Ba et al.,2 therapeutic approaches
for the conservation of teeth presenting furcation de-
fects (i.e., open flap debridement [OFD], tunneling, root
amputation, hemisection, and regeneration) are asso-
ciated with high survival rate ranges, with guided tissue
regeneration (GTR), a regenerative approach, being the
highest one with a survival rate range of 83.3% to 100%
after 5 to 12 years. These survival rates do not differ
much from implant survival rates in periodontal patients
for the same time period.17,18 Hence, understanding
when regenerative therapies are indicated for the
treatment of furcation defects in the context of a treat-
ment plan is essential to maximize predictability, cost
effectiveness, and patient satisfaction.
AIM
The aim of this review is to present and discuss the
available evidence regarding the effectiveness of dif-
ferent regenerative approaches for the treatment of
Avila-Ortiz, De Buitrago, Reddy
furcation defects in specific clinical scenarios com-
pared with conventional surgical therapy to provide
clinical guidelines for the treatment and effective
maintenance of furcation defects and to identify
priorities for future research that may aid critical
advancements in periodontal regenerative medicine.
CLINICAL SCENARIOS AND CONSIDERATION
OF TREATMENT OPTIONS
A number of classifications have been proposed to
categorize furcation involvement (summarized in
Table 1).19-26 All of them present limitations, be-
cause the marked anatomic variability of furcation
lesions makes it difficult to cover all possible clinical
scenarios in a comprehensive, but also concise,
manner. Nevertheless, the classification by Hamp
et al.19 is probably the most universal one. This is
likely attributable to its simplicity and the correlation
between the proposed degrees of severity and
commonly found clinical scenarios, which facilitates
interprofessional communication for therapeutic
purposes. Additionally, it is the most commonly used
classification in periodontal research. For these
reasons, the classification by Hamp et al.19 will be
used in this review (Fig. 1): 1) Degree/Class I: hor-
izontal loss of periodontal tissue support <3 mm; 1)
Degree/Class II: horizontal loss of periodontal tissue
support >3 mm but not through-and-through defect;
and 3) Degree/Class III: through-and-through defect.
Hence, in this review the clinical scenarios of in-
terest are as follows: 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.
MATERIALS AND METHODS
This systematic review follows the guidelines of the
PRISMA (Preferred Reporting of Systematic Reviews
and Meta-Analyses) statement.27,28
PICO (Population, Intervention, Comparison, and
Outcomes) Question
In human adults with periodontal furcation involvement
(Class I, Class II, and/or Class III according to the
classification by Hamp et al.19), are clinical, radio-
graphic, histologic, microbiologic, and patient-reported
outcomes improved with regenerative therapy com-
pared with non-regenerative surgical treatment?
Outcomes of Interest
A variety of outcomes of interest can be consid-
ered to assess the effectiveness of regenerative
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Periodontal Regeneration: Furcation Defects Volume 86 • Number 2 (Suppl.)

Table 1.
Classifications for Furcation Involvement

Publication Year and Author(s) Classification

1958 Glickman20 Grade I: soft tissue lesion extending to the entrance of the furcation but no furcal bone loss
Grade II: loss of furcal bone to varying degrees but not through and through
Grade III: through and through but not clinically visible (presence of granulomatous tissue)
Grade IV: through and through visible clinically (tunnel)

1958 Goldman21 Grade I: incipient

Grade II: cul-de-sac (pouch)
Grade III: through and through

1969 Staffileno22 Grade I: soft tissue lesion extending to the entrance of the furcation with minor degree of bone loss
Grade II: loss of furcal bone but not through and through
Grade III: through and through

1969 Easley and Drennan23
1975 Hamp et al.19
1979 Ramfjord24
1984 Tarnow and Fletcher25
Class I: incipient involvement, entrance of the furcation detectable with no horizontal bone loss
Class II, Type 1: horizontal bone loss but no vertical component
Class II, Type 2: horizontal bone loss and vertical bone loss
Class III, Type 1: through-and-through bone loss with no vertical component
Class III, Type 2: through-and-through bone loss with vertical component
Degree/Class I: horizontal loss of periodontal tissue support <3 mm
Degree/Class II: horizontal loss of periodontal tissue support >3 mm but not through and through
Degree/Class III: through-and-through defect
Degree 1: horizontal penetration <2 mm
Degree 2: horizontal penetration >2 mm but not through and through
Degree 3: through and through
Uses Grades I, II, III proposed previously by Glickman20 with an additional subclassification based on
vertical invasion from the furcation fornix:
A: VPD, 1 to 3 mm
B: VPD, 4 to 6 mm
C: VPD, >7 mm

1998 Hou et al.26 Three classes (Class I, II, and III):

Classes are the same as grades in the classification by Hamp et al.19
Two subclasses (Subclass a and b):
a: for suprabony defects
b: for infrabony defects
Three types (A, B, and C):
A: root trunk represents the cervical one-third of the root complex
B: root trunk represents half of the root complex
C: root trunk represents the cervical two-thirds of the root complex

therapies in furcation defects: 1) clinical: closed
measurements (vertical probing depth [VPD]/
horizontal probing depth [HPD] reduction and
vertical attachment level [VAL]/horizontal at-
tachment level [HAL] gain) and open measure-
ments (furcation defect fill/volume reduction,
furcation closure rate on re-entry, and long-term
tooth survival rate); 2) radiographic: furcation fill
and changes in density; 3) histologic: evidence of
periodontal regeneration and characteristics of
different tissue compartments; 4) microbiologic:
reduction of specific bacterial species; 5) patient-
reported: rate of complications, perceived benefit,
and changes in quality of life.
It must be mentioned that human histology is the
ultimate proof to demonstrate evidence of peri-
odontal regeneration, which can be defined as the
restoration of lost periodontium, evidenced by the
formation of new alveolar bone, new cementum, and
a functional periodontal ligament (PDL) on a pre-
viously diseased root surface.1,29
Literature Search Protocol
Four electronic databases were searched for publi-
cations of interest within the scope of this focused

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J Periodontol • February 2015 (Suppl.)
Figure 1.
Drawings depicting the 1975 Hamp et al.19 classification on clinical scenarios for furcation defects. versions of the studies that
literature review: 1) National Library of Medicine
(MEDLINE/PubMed); 2) Scopus; 3) Web of Knowl-
edge; and 4) the Cochrane Central Register of
Controlled Trials (CENTRAL). The search was con-
ducted from August 1, 2013 to September 1, 2013.
The search was limited to human studies published in
English. No limitation regarding study type, publi-
cation date, or publication status was set. The search
strategy used per database is displayed in Table 2.
The electronic database search was complemented
by manually searching all issues of Journal of Peri-
odontology, Journal of Clinical Periodontology, and
International Journal of Periodontics & Restorative
Dentistry from January 1990 to September 2013.
Article Eligibility Criteria
Articles reporting original studies (including, in
a non-restrictive manner, human patient clinical tri-
als, cohort studies, case series, and case reports) and
systematic reviews on the topic of periodontal re-
generative therapy in furcation defects were eligible.
Descriptive reviews and editorials were not included.
To be eligible, studies must have recruited patients
aged >18 years who had at least one furcation defect
treated with regenerative therapy. Studies that used
the same population reported in other selected
studies were not excluded, but only the study with the
longest follow-up was considered for the discussion
of the outcomes of interest. Additionally, included
studies must report at least one outcome of interest.
Given the nature of this review, which is based on
specific clinical scenarios, those clinical trials that did
not report the data separately and clearly for any of
the aforementioned scenarios were categorized as
‘‘non-classifiable,’’ and their data were not ab-
stracted. Specific for clinical trials, studies must have
Avila-Ortiz, De Buitrago, Reddy
at least one surgical control
group and one surgical exper-
imental group that involved the
application of a regenerative
approach. Finally, those arti-
cles for which full-text versions
could not be found by the ser-
vices of the University of Iowa
Library were excluded.
Article Selection and Data
Extraction
Two reviewers (GA-O and JGD)
independently read the title and
abstract of the entries yielded
from the initial electronic data-
base and hand searches. After
this initial filter, both reviewers
read separately the full-text
could be potentially included
in this review and established a final selection of
articles after applying the eligibility criteria. Any
disagreement in the final selection was resolved by
open discussion. One reviewer (GA-O) extracted the
data of the selected studies using standardized ab-
straction tables. Information extracted from each
study included the following: 1) year of publication
and first author; 2) objective; 3) study design; 4)
number of patients included; 5) intervention(s); 6)
parameters recorded; 7) duration of the study; and
8) the main findings in function of the outcomes of
interest.
RESULTS
Results of Literature Selection Process
The initial search yielded the following results: 379
entries were found in PubMed, 64 in Scopus, 856 in
Web of Knowledge, and 200 in the Cochrane Library.
The hand search did not yield any additional entries,
likely because of the specificity of the terms ‘‘furcation’’
and ‘‘furca.’’ Excluding all duplicate studies, the total
number of articles selected after reviewing the titles and
abstracts was 183. Thirty-four articles were excluded
after full-text review (Table 3).10-12,16,30-59 A final se-
lection of 150 articles was made, of which six were
systematic reviews,2,60-64 109 were clinical trials,53,65-172
27 were case series,173-199 and eight were case re-
ports.200-207 No cohort studies were identified. A total
of 24 clinical trials149-172 and 13 case series185-197
were non-classifiable, as defined in Materials and
Methods (Tables 4 and 5). Of the 85 remaining clinical
trials,53,65-148 eight reported outcomes after applying
regenerative therapy on maxillary facial/interproximal
Class II furcation defects,76,87,92,100,105,140,148,208
68 on mandibular facial/lingual Class II furcation
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Periodontal Regeneration: Furcation Defects
Table 2.
Search Strategy per Database
Database Search Strategy
PubMed TITLE-ABS-KEY [periodontal
regeneration] AND [furca*]
Filters: Human; English; no limit set for
date of publication
Scopus TITLE-ABS-KEY (‘‘furcation defect’’ OR
‘‘furcation involvement’’ AND
‘‘periodontal regeneration’’) AND
(LIMIT-TO (EXACTKEYWORD,
‘‘Human’’) OR LIMIT-TO
(EXACTKEYWORD, ‘‘Humans’’))
AND (LIMIT-TO (LANGUAGE,
‘‘English’’))
Web of Knowledge Topic = (‘‘furcation defect’’ OR ‘‘furcation
involvement’’ AND ‘‘periodontal
regeneration’’)
Refined by: Document types =
(ARTICLE OR CLINICAL TRIAL OR
CASE REPORT OR REVIEW OR
ABSTRACT) AND Languages =
(ENGLISH) AND Topic = (human)
Cochrane Library TITLE-ABS-KEY ‘‘furcation defect’’ OR
‘‘furcation involvement’’ AND
‘‘periodontal regeneration’’
defects,65-68,70-72,75,77,78,80-85,87-90,93-99,101-104,106,107,
110-112,114-122,124-139,141-147 one on maxillary Class III
furcation defects,91 nine on mandibular Class III fur-
cation defects,69,73,74,77,86,108,109,113,123 and one on
maxillary premolars presenting Class I and Class II
furcation defects.79 Of the 14 selected case series,
two reported on the treatment of maxillary facial/
interproximal Class II furcation defects,177,180 11 on
mandibular facial/lingual Class II furcation defects,173-
176,178-184 and two on mandibular Class III furcation
defects.198,199 Of the eight case reports, two described
the use of regenerative therapies on maxillary facial/
interproximal Class II furcation defects,204,206 six on
mandibular facial/lingual Class II furcation de-
fects,200,201,203-205,207 and one on mandibular Class III
furcation defects.202 None of the identified original
articles reported on the application of regenerative
approaches in maxillary or mandibular Class I fur-
cation defects in molars. This process of literature
selection and article allocation is depicted in Figure 2.
In the final selection, two clinical trials,77,87 one case
report,204 and one case series180 reported the out-
comes of regenerative therapy in different clinical
scenarios separately but in the same article, which
explains the apparent discrepancy in the numbers
displayed in Figure 2 (marked with an asterisk).
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Volume 86 • Number 2 (Suppl.)
Summary of Previous Systematic Reviews
Main findings in previously published systematic
reviews2,60-63 on this topic are consistent in the
conclusion that regenerative therapies are more ef-
fective than non-regenerative surgical approaches in
the treatment of furcation defects.
Jepsen et al.60 conducted a systematic review
published in 2002 that aimed at assessing the effi-
cacy of GTR in the treatment of furcation defects
compared with conventional surgical approaches,
such as OFD. The primary outcome was horizontal
furcation defect fill on re-entry. A total of 14 studies
reporting different clinical scenarios (i.e., Class II and
III defects) were selected. Meta-analyses were con-
ducted. It was observed that GTR was superior to
OFD in the treatment of mandibular Class II furca-
tions (mean difference: 1.51 mm) and maxillary
Class II furcations (mean difference: 1.05 mm). The
same trend was observed for other secondary out-
comes assessed, such as VPD reduction, HPD re-
duction, and VAL gain. Regarding Class III defects,
the authors concluded that there are limited data on
the effectiveness of regenerative therapy.
In 2003, Murphy and Gunsolley 61 published
a systematic review with the objective of assessing
the efficacy of GTR procedures in patients with
periodontal osseous defects (i.e., intrabony and
furcations) compared with surgical controls on
clinical, radiographic, adverse, and patient-reported
outcomes. For furcations, the primary outcomes
were VAL gain, VPD reduction, recession (REC)
changes, vertical defect fill, and horizontal defect fill
(open attachment gains). Meta-analyses were con-
ducted to determine the differences between both
treatment modalities for all these outcomes. It was
found that GTR yields significantly superior results in
terms of VAL gain (0.86 mm), VPD reduction (0.8
mm), and horizontal defect fill (1.06 mm). In-
terestingly, it was also observed that the addition of
a bone graft substitute to the use of a barrier mem-
brane enhanced the clinical outcomes for furcation
defects but not in intrabony defects. Other outcomes,
such as long-term tooth survival, radiographic
changes, or furcation closure, could not be analyzed
in a pooled quantitative manner because of limited
data available.
In the same year, Reynolds et al.62 presented
a systematic review aimed at assessing the efficacy
of bone replacement grafts in the treatment of os-
seous defects (i.e., intrabony and furcations) rela-
tive to OFD and other non-regenerative surgical
therapies. The effect of different grafting materials
(i.e., alloplastic bone substitutes, allografts, and
autografts) on clinical (VPD reduction, VAL gain,
REC changes, and furcation defect fill), radio-
graphic, histologic, and patient-reported outcomes
J Periodontol • February 2015 (Suppl.) Avila-Ortiz, De Buitrago, Reddy

Table 3.
Articles Excluded Based on Full-Text Review and Reason for Exclusion

Publication Year and Author(s) Reason for Exclusion

10
1980 Ross and Thompson Regeneration outcomes were not assessed
30
1991 Machtei Descriptive review

1992 Lu31 In vitro study

32
1993 Caffesse et al. Animal study

1994 Machtei et al.33 No surgical control group

1994 Wang et al.11 Retrospective study

34
1995 Anderegg et al. Regeneration outcomes were not assessed

1995 Carnevale et al.35 Descriptive review

36
1995 Froum and Tarnow Technique report: regeneration outcomes were not assessed
12
1995 Müller et al. Retrospective study

1996 Evans et al.58 Descriptive review

59
1997 Müller and Eger Retrospective study
37
1997 Wang et al. No surgical control group

1998 Giannobile et al.38 Animal study

39
1998 Kim Descriptive review

1999 Karring and Cortellini40 Descriptive review

2000 Ling et al.41 Full text not in English

42
2000 McClain and Schallhorn Descriptive review

2000 Sanz and Giovannoli43 Descriptive review

2000 Yan et al.44 No parameters of interest were reported

16
2001 Ehnevid and Jansson Retrospective study

2001 Fowler and Breault45 Not a regenerative approach

46
2001 Mengel et al. Full text not in English
47
2002 Chung et al. Descriptive review

2003 Machtei et al.48 No surgical control group

49
2003 Trombelli et al. No regenerative approach was applied
50
2005 Novaes et al. Descriptive review

2006 Hovey et al.51 Animal study

52
2006 Tsao et al. Secondary outcomes from the same population included in another selected study

2009 Casarin et al.53 Secondary outcomes from the same population included in another selected study

2011 Verma et al.54 No regenerative approach was compared with a control

55
2012 Gkranias et al. Animal study

2013 de Miranda et al.56 No regenerative approach was applied

2013 Pradeep et al.57 No regenerative approach was applied

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Periodontal Regeneration: Furcation Defects Volume 86 • Number 2 (Suppl.)

Table 4.
Non-Classifiable Clinical Trials on the Effect of Regenerative Therapy for the Treatment
of Furcation Defects in Different Anatomic Locations

Publication Year and Author(s) Reason for Not Being Classifiable

1991 Anderegg et al.149 Pooled the results of maxillary and mandibular facial Class II and III furcation defects
150
1991 Flanary et al. Pooled the results of maxillary and mandibular facial Class II furcation defects
1992 Twohey et al.151 Pooled the results of maxillary and mandibular facial and lingual Class II furcation
defects
1993 van Swol et al.152 38 patients with at least one Class II furcation defect but not clear whether the
defects were maxillary or mandibular nor whether they were facial, lingual, or
interproximal

1994 Black et al.153 13 patients with 13 pairs of Class II furcation defects but not clear whether the
defects were maxillary or mandibular nor whether they were facial, lingual, or
interproximal

1994 Caton et al.154 Pooled the results of maxillary and mandibular facial and lingual Class II furcation
defects
1995 Christgau et al.155 Pooled the results of Class I and III furcation defects

1995 Hugoson et al.156 Pooled the results of maxillary and mandibular facial and lingual Class II furcation
defects
1996 Yukna and Yukna157 Pooled the results of maxillary and mandibular facial and lingual Class II furcation
defects
1997 Eickholz et al.159 Patients presenting maxillary and mandibular Class II and III furcation defects were
enrolled, but data were not stratified by location (e.g., mandibular or maxillary) for
the final analysis

1997 Eickholz and Hausmann158 Patients presenting maxillary and mandibular Class II and III furcation defects were
enrolled, but data were not stratified by location (e.g., mandibular or maxillary) for
the final analysis

1997 Garrett et al.160 Pooled the results of maxillary and mandibular Class II furcation defects
1997 Howell et al.161 Patients presenting Class II furcation defects were enrolled, but the location (e.g.,
mandibular or maxillary) was not specified

1998 Eickholz and Kim162 Patients presenting maxillary and mandibular Class II and III furcation defects were
Note: 24-month follow-up of the enrolled, but data were not stratified by location (e.g., mandibular or maxillary) for
1997 study158 the final analysis

1998 Vernino et al.163 Pooled the results of maxillary and mandibular Class II furcation defects
164
1999 Eickholz and Hausmann Patients presenting maxillary and mandibular Class II and III furcation defects were
Note: 24-month follow-up of the enrolled, but data were not stratified by location (e.g., mandibular or maxillary) for
1997 study158 the final analysis

1999 Vest et al.165 Pooled the results of maxillary and mandibular Class II furcation defects
2000 Eickholz et al.166 Patients presenting maxillary and mandibular Class II furcation defects were enrolled,
but data were not stratified by location (e.g., mandibular or maxillary) for the final
analysis
2001 Eickholz et al.167 Patients presenting maxillary and mandibular Class II furcation defects were enrolled,
Note: 5-year follow-up of the 1997 study,158 but data were not stratified by location (e.g., mandibular or maxillary) for the final
including a subpopulation of the original study analysis

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Table 4. (continued )
Non-Classifiable Clinical Trials on the Effect of Regenerative Therapy for the Treatment
of Furcation Defects in Different Anatomic Locations

Publication Year and Author(s) Reason for Not Being Classifiable

2001 Lamb et al.168 Although most defects were mandibular, the outcomes after the treatment of
maxillary and mandibular Class II furcation defects were pooled in the final data
analysis
2002 Eickholz and Hausmann169 Pooled the results of intrabony and furcation defects

2003 Palioto et al.170 Patients presenting Class III furcation defects were enrolled, but the location (e.g.,
mandibular or maxillary) was not specified
2004 Horwitz et al.171 Pooled the results of maxillary and mandibular Class II furcation defects
172
2006 Eickholz et al. Patients presenting maxillary and mandibular Class II furcation defects were enrolled,
Note: 10-year follow-up of the 1997 study,158 but data were not stratified by location (e.g., mandibular or maxillary) for the final
including a subpopulation of the original study analysis

was considered. Although no meta-analyses

Table 5.
Non-Classifiable Case Series on the Effect of
Regenerative Therapy for the Treatment of
Furcation Defects in Different Anatomic Locations
Publication Year and Author(s)
1976 Mellonig et al.185
1978 Sepe et al.186
1983 Sanders et al. 187
1992 Han188
1995 Polson et al.189
1995 Yamanouchi et al.190
1996 Becker et al.191
1997 Yukna and Yukna192
1999 Rosen and Reynolds193
1999 Vernino et al.194
2000 Camelo et al.195
2003 Nevins et al.196
197
2012 Nevins et al.
Reason for Not Being Classifiable
The clinical scenario was not specified
The clinical scenario was not specified
The clinical scenario was not specified
Pooled the results of maxillary and
mandibular Class II furcation defects
Pooled the results of maxillary and
mandibular Class II furcation defects
Pooled the results of different clinical
scenarios
Pooled the results of maxillary and
mandibular Class II furcation defects
Pooled the results of maxillary and
mandibular Class II furcation defects
Pooled the results of different clinical
scenarios
Pooled the results of maxillary and
mandibular Class II furcation defects
Pooled the results of different clinical
scenarios
The clinical scenario was not specified
Pooled the results of different types of
periodontal defects
were conducted because of heterogeneity
and insufficient data available, it was gen-
erally observed that superior clinical out-
comes were attained when bone grafts were
used compared with non-regenerative ap-
proaches.
Huynh-Ba et al.2 published a systematic
review in 2009 with the objective of de-
termining the survival rate and incidence of
complications of multirooted teeth presenting
furcation defects after a mean observation
period of ‡5 years after completion of active
periodontal therapy. A total of 22 articles
were included. Because of heterogeneity
among all the selected studies in this sys-
tematic review, no meta-analysis was per-
formed. However, it was found that, among
a variety of treatment modalities, including
OFD, tunneling, root amputation, hemisection,
and GTR, long-term survival rate range asso-
ciated with GTR was high (i.e., 83% to 100%
after 5 to 12 years when considering four
different studies169,172,192,209).
In 2011, Kinaia et al.63 published a sys-
tematic review aimed at assessing the effec-
tiveness of various methods for the treatment
of Class II furcation defects based on surgical
re-entry outcomes, specifically VPD reduction,
VAL gain, horizontal defect fill, and vertical
defect fill. A total of 13 articles were selected.
Five of these articles compared the effective-
ness of non-absorbable membranes with OFD,
three articles compared absorbable mem-
branes with OFD, and five articles compared
non-absorbable with absorbable membranes.

S115
Periodontal Regeneration: Furcation Defects
Figure 2.
Flowchart displaying the search process and article selection. *Indicates more than one clinical scenario presented in a single article, accounting for the
apparent discrepancy in numbers.
Meta-analyses were conducted to assess the differ-
ences among groups in these three categories for all
the outcomes of interest. It was found that GTR using
a non-absorbable membrane was significantly superior
to OFD in terms of VPD reduction (0.75 mm), VAL gain
(1.41 mm), horizontal defect fill (1.16 mm), and vertical
defect fill (0.58 mm). Conversely, GTR using an
absorbable membrane was significantly superior to
OFD in terms of VPD reduction (0.73 mm), VAL gain
(0.88 mm), horizontal defect fill (0.98 mm), and
vertical defect fill (0.78 mm). Finally, GTR using an
absorbable membrane was slightly superior to GTR
using a non-absorbable membrane in terms of VPD
reduction (0.25 mm), VAL gain (0.39 mm), horizontal
defect fill (0.29 mm), and vertical defect fill (0.33 mm),
although these differences were not significant.
In 2013, Chen et al.64 published a systematic re-
view aimed at assessing the evidence on the efficacy
of GTR with or without osseous grafting for the
treatment of Class II furcation defects. A total of 20
studies were selected, of which 13 studies were ran-
domized clinical trials (RCTs) comparing OFD with
GTR, four studies were RCTs comparing OFD with
GTR plus bone graft, and six studies were RCTs
comparing GTR with GTR plus bone graft. The out-
comes of interest were furcation closure rate, HAL,
VAL, horizontal bone fill (HBF), and vertical bone fill
S116
Volume 86 • Number 2 (Suppl.)
(VBF). A meta-analysis was conducted for all the
outcomes, except for furcation closure and HAL gain
in maxillary Class II defects. Regarding furcation
closure in mandibular defects, the results indicated
that GTR + bone graft was the most effective thera-
peutic approach. Regarding HAL gain in mandibular
molars, the weighted mean difference between GTR
and OFD was 1.15 mm (in favor of GTR), between
GTR + bone graft and OFD was 1.76 mm (in favor
of GTR + bone graft), and between GTR + bone graft
and GTR was 0.66 mm (in favor of GTR + bone graft).
Regarding VAL gain in maxillary molars, the weighted
mean difference between GTR and OFD was 1.02 mm
(in favor of GTR), but there was not sufficient data to
compare the rest of the therapeutic modalities.
Regarding VAL gain in mandibular molars, the
weighted mean difference between GTR and OFD
was 1.53 mm, between GTR + bone graft and OFD
was 1.53 mm (in favor of GTR + bone graft), and
between GTR + bone graft and GTR was 0.47 mm (in
favor of GTR + bone graft). In terms of HBF in max-
illary furcation defects, the weighted mean difference
between GTR and OFD was 0.72 mm (in favor of
GTR), and there was not sufficient information to
analyze the difference between the other therapeutic
modalities. Regarding HBF in mandibular molars, the
weighted mean difference between GTR and OFD was
J Periodontol • February 2015 (Suppl.)
1.55 mm, between GTR + bone graft and OFD was
1.34 mm (in favor of GTR + bone graft), and between
GTR + bone graft and GTR was 0.86 mm (in favor of
GTR + bone graft). In terms of VBF in maxillary Class II
furcation defects, the weighted mean difference be-
tween GTR and OFD was 0.71 mm (in favor of GTR),
but there was not sufficient data to compare the rest of
the therapeutic modalities. Finally, regarding VBF in
mandibular molars, the weighted mean difference
between GTR and OFD was 1.46 mm, between GTR +
bone graft and OFD was 1.77 mm (in favor of GTR +
bone graft), and between GTR + bone graft and GTR
was 0.87 mm (in favor of GTR + bone graft). The
results of this study illustrate the overall superiority of
GTR in combination with a bone graft compared with
both OFD and GTR alone.
Available Evidence on Specific Clinical Scenarios
Maxillary (facial or interproximal) Class II furcation
defects. A total of eight articles reporting clinical
trials aimed at assessing the effectiveness of re-
generative therapies in the treatment of maxillary
facial or interproximal Class II furcation defects were
identified (see supplementary Table 1 in online
Journal of Periodontology).76,87,92,100,105,140,148,208
Three studies included both facial and proximal de-
fects,76,87,92 one study included facial defects exclu-
sively,105 and four studies only included proximal
defects.100,140,148,208 One study compared two dif-
ferent regenerative approaches.148 The rest compared
a regenerative approach (test) with at least one non-
regenerative surgical intervention consisting of OFD or
coronally positioned flap (CPF).76,87,92,100,105,140,208
Six of the studies had a split-mouth design, and two
studies followed a parallel-groups protocol.105 No
study reported a sample size calculation. Five
studies reported outcomes after a follow-up period
of 6 months,76,87,92,148,208 one study had a duration
of 9 months,100 one study ran for 12 months,105 and
one article presented results after a 24-month
follow-up period.140 Two articles included the same
patient population, so only the outcomes reported
in the study with the longest follow-up will be
discussed. 140
All the clinical trials reported clinical outcomes. Of
the six selected studies that compared the effective-
ness of regenerative therapy with non-regenerative
approaches, five included the use of a membrane in
the test group.76,87,92,100,105 In all these studies, the
membrane used was non-resorbable (expanded pol-
ytetrafluoroethylene [ePTFE]), and only in one study
was a bone grafting material (hydroxyapatite [HA]
particles) used in combination with the membrane.105
The majority of the GTR-only studies reported superior
outcomes in the test group in terms of probing depth
(PD) reduction, attachment gain, and furcation defect
Avila-Ortiz, De Buitrago, Reddy
fill, but the differences were not significant, generally
in the range of 0.5 to 1 mm.76,87,92 Only Avera
et al.100 reported a significant improvement in VAL
gain of 1.5 mm in favor of the test group. This study
included only mesial defects. Interestingly, among the
three studies that included facial and proximal defects,
only one study reported the results in these two an-
atomic locations separately, indicating that a benefi-
cial effect of both therapies was only seen on facial
defects.92
The study that assessed the efficacy of GTR in
combination with HA particles in the treatment of
maxillary facial Class II furcation defects compared
this therapy with two control groups (OFD and
CPF).105 The three therapeutic modalities led to
improvements after 12 months from baseline, but it
was found that the average VPD reduction was 1.53,
1.4, and 2.43 mm, the average VAL gain was 0.63,
1.17, and 1.57 mm, and the HAL gain was 1.03, 1.40,
and 2.13 mm for the OFD group, the CPF group, and
the test group, respectively. The findings in this study
illustrate the superiority of regenerative therapy via
GTR and a bone graft for this particular scenario
compared with proximal sites. Whether this beneficial
effect is mainly dependent on the use of a bone graft
or on the location of the furcation defects (only facial)
cannot be assessed properly because other studies of
similar characteristics in the treatment of proximal
sites could not be identified. In this context, it is
important to consider that, among the plethora of
factors that may affect outcomes in the treatment of
proximal Class II furcation defects, difficulties in
barrier membrane adaptation and limited access
may play an important role in the observed outcomes
compared with facial sites.177
Only one study assessed radiographic outcomes
(radiographic bone fill [BF] in mesial defects), re-
porting minimal differences between groups after a
9-month healing period.100 None of the selected ar-
ticles reported on microbiologic, histologic, or patient-
reported outcomes.
Two case series on the application of regenerative
therapies in the treatment of maxillary facial or in-
terproximal Class II furcation defects were identified
(see supplementary Table 2 in online Journal of
Periodontology).177,180 The earliest case series re-
ported the treatment of a total of 15 interproximal
Class II defects with different combinations of dem-
ineralized freeze-dried bone allograft (DFDBA), cal-
cium sulfate, and ePTFE membrane.176 Significant
clinical improvements in PD and clinical attachment
level (CAL) were reported, and the furcation defect
closure was observed in 11 of the 15 cases. In this
study, the follow-up time varies from 6 to 45 months.
The other case series included one patient presenting
a Class II furcation defect on the mesio-palatal aspect
S117
Periodontal Regeneration: Furcation Defects
of a maxillary first molar.180 The applied therapy
consisted of an OFD approach along with the ap-
plication of DFDBA in combination with recombinant
human platelet-derived growth factor-BB (rhPDGF-
BB; 1.0 mg/mL). At 9 months postoperatively, a gain in
attachment of 4 mm was observed, with no concomitant
REC, whereas VPD and HPD were both 2 mm. Histologic
evidence of the formation of new attachment, including
cementum, alveolar bone, and PDL, was shown. No
radiographic, microbiologic, or patient-reported out-
comes were reported.
Two case reports illustrating the use of regenerative
therapies in the treatment of maxillary facial or
interproximal Class II furcation defects were iden-
tified (see supplementary Table 3 in online Journal
of Periodontology).204,207 Both case reports pre-
sented one facial maxillary Class II defect
each.204,207 In both reports, clinical improvements
after regenerative therapy were observed, demon-
strated by PD reduction and CAL gain. Interestingly,
histologic evidence of complete periodontal re-
generation of the furcation defect was demonstrated
in one of the case reports.204 None of the selected
articles reported on microbiologic, radiographic, or
patient-reported outcomes.
Mandibular facial/lingual Class II furcation
defects. A total of 68 articles reporting clinical
trials aimed at assessing the effectiveness of re-
generative therapies in the treatment of mandibular
facial or lingual Class II furcation defects were
identified (see supplementary Table 4 in online
Journal of Periodontology).65-68,70-72,75,77,78,79-
85,87-90,93-99,101-104,106,107,110-112,114-122,124-139,141-147
Thirty-seven studies compared a non-regenerative
surgical intervention consisting of OFD or CPF
(control) with at least one regenerative approach
(test).65-68,70,71,75,77,78,83,85,87,89,93,94,102,103,107,112,118,
120-122,126,128,129,132-134,137,138,141-143,145-147 Of these
37 studies, 17 included at least one test group
consisting of OFD or CPF plus a barrier membrane
alone,67,68,70,71,78,85,87,89,93,94,107,118,120,122,129,142,145
eight had at least one test group consisting of OFD or
CPF + bone graft alone,65,66,77,103,126,132,133,147 six
included at least one test group consisting of OFD or
CPF + bone graft in combination with a mem-
brane,112,129,132,138,143,147 four included at least one
test group consisting of OFD or CPF in combina-
tion with a bioactive agent alone,133,135,141,146 and
six had at least one test group consisting of OFD or
CPF + other regenerative therapies encompassing
a variety of grafting materials and chemothera-
peutics.75,94,102,121,128,129 It is important to men-
tion that some studies had more than one test
group.94,129,132,146,147 Within these 37 selected
studies, 13 were performed only in facial furcation
defects, 65,68,75,83,85,102,103,121,128,137,141,142,146
S118
Volume 86 • Number 2 (Suppl.)
whereas 24 included both facial and lingual loca-
tions.66,67,70,71,77,78,87,89,93,94,107,112,118,120,122,126,129,132-
134,138,143,145,147 None of the selected studies was
conducted on lingual defects exclusively. Finally, it is
important to remark that all of the 37 selected studies
reported on clinical outcomes and nine included ra-
diographic outcomes, 85,93,94,120,129,134,137,141,146
whereas only one study reported microbiologic out-
comes,94 and none of them did so on histologic or
patient-reported outcomes.
Of the 17 clinical trials that included at least
one test group consisting of OFD or CPF + barrier
membrane alone, nine used a non-absorbable
membrane. 67,68,7,85,87,93,94,107,118 All of these
studies reported clinical outcomes of interest that
were assessed at baseline and at different time points,
with a maximum follow-up length of 24 months in
only one study.93 It was generally observed that both
the control and test therapies lead to improvements
from baseline in all parameters analyzed, but GTR
therapy was associated with significantly superior
results (typically >1 mm) compared with the control
in terms of VPD reduction, VAL/HAL gains, and BF.
Two studies reported radiographic outcomes.85,94 No
significant differences in terms of radiographic bone
density changes were observed between groups in
both studies. Only one study reported microbiologic
outcomes.94 Interestingly, it was found that sites
treated with an ePTFE barrier ‘‘tended to be positive
for target microorganisms more often than the sites
that were treated without a membrane,’’ independently
of the administration of a systemic antibiotic (i.e.,
ornidazole). These findings contrast with those re-
ported by other investigators, who observed that the
placement of an absorbable collagen membrane in
the treatment of mandibular Class II furcation defects
does not affect the characteristics of the subgingival
microflora.37
Of the 17 clinical trials that included at least one
test group consisting of OFD or CPF + barrier
membrane alone, eight used an absorbable mem-
brane.71,78,89,120,122,129,142,145 All these clinical trials
reported clinical outcomes. The maximum follow-up
was 24 months.120 The findings were not as con-
sistent among studies as those reported for non-
absorbable barrier membranes. Six studies observed
superior clinical outcomes in the test group for the
majority of parameters analyzed,78,120,122,129,142,145
whereas one study showed comparable results be-
tween both groups, except for significantly higher BF
on re-entry in the test group,89 and another one re-
ported superior results in the control group, partic-
ularly for furcation defect fill (70% versus 38%).71 It is
worth noting that, similar to the observations reported
in studies focused on non-absorbable membranes,
the magnitude of the difference between groups in
J Periodontol • February 2015 (Suppl.)
studies that found significantly better results in the
sites treated with an absorbable membrane was
typically >1 mm. Radiographic outcomes were re-
ported in three articles. Two studies revealed better
results in the test group in terms of radiographic
furcation defect fill and density,120,129 whereas in the
remaining study, the radiographic outcomes could
not be analyzed because of the inadequacy of the
obtained images.142
Eight clinical trials included at least one test
group consisting of OFD or CPF + bone graft
alone.65,66,77,103,126,132,134,147 Three of these studies
applied an allograft,65,132,147 three used an allo-
plastic material,66,77,103 and two involved the use of
a xenograft.126,134 All these studies reported clinical
outcomes but no other parameters of interest (i.e.,
radiographic, histologic, microbiologic, and patient-
reported). Five of the studies (three using an allo-
plastic material,66,77,103 one evaluating the efficacy
of an allograft,132 and one using a xenograft126)
demonstrated that both therapies were associated
with a beneficial effect, because the test group
showed significantly superior results in terms of VPD
reduction, VAL gain, and furcation defect fill on
surgical re-entry. The other three studies showed that
both therapies lead to an improvement from baseline,
but the use of a bone grafting material per se did not
provide an additional benefit to the control ther-
apy.65,134,147 However, it is important to note that the
sites treated with flap advancement and root condi-
tioning (citric acid) with or without DFDBA in the
study by Gantes et al.65 were reassessed again after 5
years.210 It was found that the majority of sites (12 of
16) that were closed at the 6-month evaluation were
not closed anymore. In other words, the furcation
defects recurred, which raises questions about the
long-term stability of regenerative results obtained
with CPFs. None of these eight studies reported on
microbiologic, radiographic, histologic, or patient-
reported outcomes.
Six clinical trials had at least one test group
consisting of OFD or CPF + bone graft in combination
with a barrier membrane.112,129,132,138,143,147 All
these studies reported clinical outcomes, but only one
presented radiographic outcomes. 129 Both absorb-
able and non-absorbable membranes were used.
Grafting materials applied included alloplastic ma-
terials, allografts, and xenografts. None of the
different biomaterial combinations was repeated.
Therefore, the establishment of a comparison be-
tween these studies is not reasonable. However, it
must be mentioned that all the studies consistently
showed that the regenerative intervention was sig-
nificantly superior to the control therapy (i.e., OFD
in all of them) in the majority of the parameters
analyzed.
Avila-Ortiz, De Buitrago, Reddy
Four clinical trials included at least one test group
consisting of OFD or CPF in combination with a bi-
ologic agent alone.132,137,141,146 One of them com-
pared OFD with OFD in combination with an enamel
matrix derivative (EMD) gel. The application of EMD
was found to be beneficial in all parameters analyzed
with slightly superior results (<1 mm) for VPD re-
duction, VAL gain, and vertical defect fill and more
robust improvements (>1 mm) on HAL and hori-
zontal defect fill. The other three studies, which in-
terestingly were published by the same group of
investigators, aimed at evaluating the efficacy of
OFD in combination with autologous blood-derived
products (i.e., platelet-rich plasma [PRP] or plasma-
rich fibrin [PRF]) using OFD alone as a con-
trol.137,141,146 These studies, which reported both
clinical and radiographic outcomes, found that the
application of PRP and PRF indistinctively leads to
superior, generally significant, results compared with
the control in all the parameters analyzed.
A total of 11 case series on the application of
regenerative therapies in the treatment of mandibular
facial or lingual Class II furcation defects were
identified (see supplementary Table 5 in online
Journal of Periodontology).173-176,178-184 Of these
11 studies, six reported the use of OFD/CPF in
combination with a membrane alone.173-176,178,182
Each one of the five remaining studies applied
a different regenerative approach: one combined
a non-absorbable membrane with an allograft
(DFDBA),179 one reported the use of DFDBA in
conjunction with rhPDGF-BB,180 another one only
applied EMD,181 one study described the use of EMD
in combination with autologous bone,183 and another
study tested the effect of applying porous titanium
granules (PTGs) as a defect filler.184 Of the six studies
that applied OFD/CPF and a membrane alone, four
used an absorbable membrane,173,175,178,182 and
two used a non-absorbable membrane.174,176 The
duration of the selected case series ranged from 6 to
48 months.
All the selected case series reported on clinical
outcomes. Only two studies reported radiographic
outcomes, one study reported microbiologic out-
comes, and another one did so for histologic out-
comes. None of the selected articles reported on
patient-reported outcomes. In all the case series, it
was consistently observed that clinical parameters
significantly improved from baseline, except in one
study that reported no significant improvements in all
the parameters analyzed (vertical furcation depth
[VFD], horizontal furcation depth [HFD], CAL gain,
and REC) with the exception of PD reduction.184
Radiographic outcomes reported in two studies in-
dicated that the applied regenerative therapy was
effective in increasing the bone density and vertical
S119
Periodontal Regeneration: Furcation Defects
furcation fill.183,184 The only study that reported
microbiologic outcomes found that counts of Ag-
gregatibacter actinomycetemcomitans and Porphyr-
omonas gingivalis showed a continuous decline over
a period of 48 months, whereas Prevotella inter-
media–infected and Tannerella forsythia–infected
sites remained almost unchanged in terms of path-
ogens load.176 Interestingly, histologic evidence of
complete periodontal regeneration in a mandibular
Class II defect was demonstrated in the case series
that described the use of DFDBA in combination with
a biologic agent, in this case rhPDGF-BB.180
A total of six case reports illustrating the use of
regenerative therapies in the treatment of maxillary
facial or interproximal Class II furcation defects were
identified (see supplementary Table 6 in online
Journal of Periodontology). 200,201,203-207 Of
these six articles, one reported the use of OFD/CPF
and a bioabsorbable membrane alone, 203 one
combined a bioabsorbable membrane with an allo-
graft (DFDBA),201 and another one used a combi-
nation of a bioabsorbable membrane with an allograft
(DFDBA) and an alloplastic material (HA).204 Of the
three remaining case reports, one described a tech-
nique that consisted of using a mucoperiosteal ro-
tated flap as a membrane,200 another one used EMD
in combination with autologous bone,205 and the
most recent study used autologous bone covered
with a buccal fat pad.207 The duration of the case
reports selected for this clinical scenario ranged from
6 to 25 months.
All the selected studies reported on clinical out-
comes.200,201,203-205,207 In all the cases presented,
significant improvements in the clinical parameters
evaluated were observed (see supplementary Table
6 in online Journal of Periodontology). One study
assessed radiographic outcomes, observing almost
complete closure of the furcation defect at 12
months after intervention.207 Of the three studies
that reported histologic outcomes,201,203,204 only in
one was evidence of complete periodontal re-
generation shown in a mandibular Class II furcation
defect.203 In the other two studies,201,204 conducted
by the same author, partial periodontal regeneration
was observed, but the most extended pattern of
healing was repair. None of the selected articles
reported on microbiologic or patient-reported out-
comes.
Maxillary Class III furcation defects. Only one
clinical trial91 in the context of the application of
regenerative therapies for the treatment of maxillary
Class III furcation defects was identified (see sup-
plementary Table 7 in online Journal of Periodon-
tology). This classic study aimed at assessing the
effectiveness of GTR therapy (OFD + ePTFE
membrane) in the treatment of mesial-to-distal
S120
Volume 86 • Number 2 (Suppl.)
Class III furcation defects compared with a control
(OFD alone). After a split-mouth design, a total of 11
patients, who contributed a pair of comparable de-
fects each, were recruited. Only clinical outcomes
were reported. Both groups showed similar results
in all parameters analyzed, including a modest VPD
reduction (1.7 to 2 mm) and an anecdotal VAL gain
range (0.5 to 0.1 mm). A significant increase in REC
was observed in both groups. Re-entry surgeries at 6
months revealed that the distance between the ce-
mento-enamel junction (CEJ) and the base of the defect
(BD) decreased by 1 mm in five sites of the control
group and in only one site of test group.
Mandibular Class III furcation defects. A total of
nine articles reporting clinical trials aimed at as-
sessing the effectiveness of regenerative therapies in
the treatment of mandibular Class III furcation defects
were identified (see supplementary Table 8 in online
Journal of Periodontology).69,73,74,77,86,108,109,113,123 Six
studies compared a regenerative approach (test) with
one non-regenerative surgical intervention consisting
of OFD or CPF (control).69,73,74,77,108,113 The other
three studies compared at least two different re-
generative approaches with each other.86,109,123 Five
studies had a split-mouth design, 69,73,77,108,109
whereas the rest followed a parallel-groups protocol. No
study reported a sample size calculation. The follow-
up period ranged from 16 to 60 weeks.73,86
All of the six selected studies that compared the
effectiveness of regenerative therapy with non-
regenerative approaches reported on clinical out-
comes. 69,73,74,77,108,113 Interestingly, only one study
included the use of a membrane in the test group.69 In
this study, which aimed at assessing the efficacy of
OFD plus an ePTFE barrier compared with OFD
alone, it was observed that both therapies were
associated with a positive response to therapy.
However, the test group showed significantly su-
perior results in terms of average HAL gain, as il-
lustrated by an average difference between groups
of 2 mm at both the facial and lingual sites. Also,
the number of resolved defects in the test group (18
of 21) was significantly higher than in the control
group (10 of 21). In four of the other five clinical
trials, some type of bone grafting material was used
in the test group.74,78,108,113 The results in these
studies are conflicting, because two of them re-
ported significantly superior outcomes in the test
group,77,108 whereas the other two clinical trials
showed no benefit associated with the use of a bone
graft.74,113 In the remaining clinical trial, OFD was
compared with OFD in combination with citric acid
for root conditioning and autologous fibronectin.73
Both groups were associated with a moderately
positive response, with no differences among
groups. It is important to remark that only four
J Periodontol • February 2015 (Suppl.)
patients were enrolled and the follow-up period was
16 weeks, which places this study in a lower level of
evidence.
One study included the assessment of radio-
graphic outcomes, particularly on changes of the
furcation defect area measured on non-standardized
periapical radiographs, as part of the methodol-
ogy.108 However, the data for this outcome are not
reported clearly in Results. None of the clinical trials
comparing regenerative with non-regenerative ther-
apies for the treatment of mandibular Class III fur-
cation defects reported on microbiologic, histologic,
or patient-reported outcomes.
Unlike the very limited evidence available to
support the indication of regenerative therapy in the
management of maxillary Class III furcation defects,
it appears that the treatment of mandibular Class III
furcation defects by means of regenerative ap-
proaches is substantiated by the selected literature.
Nevertheless, questions, such as whether the positive
clinical results observed in some of these clinical
trials are predictable, were they influenced by the
type of biomaterial applied, or whether it would be
beneficial to combine a barrier membrane with
a bone graft, could not be answered given the limited
number of well-conducted clinical trials available for
this clinical scenario and the marked heterogeneity
among the existing ones.
Two case series on the application of regenerative
therapies in the treatment of mandibular Class III
furcation defects were found (see supplementary
Table 9 in online Journal of Periodontology).198,199 In
one of these studies,198 a total of seven defects were
treated with a regenerative approach that consisted
of OFD, followed by root conditioning with tetracy-
cline and a combination of DFDBA particles and an
ePTFE membrane. The follow-up period was 12
months. Clinical and radiographic outcomes were
reported. Clinically, a general improvement evi-
denced by mean PD reductions (facial side, 3.5 mm;
lingual side, 4 mm) and CAL gains (facial side, 0 to 5
mm; lingual side, 2 to 7 mm) was observed. A modest
increase in radiopacity and BF in the defects was
observed radiographically. The most recent case
series described the treatment of four mandibular
molars presenting a Class III furcation defect.199 The
regenerative therapy used consisted of a CPF ap-
proach in combination with b-tricalcium phosphate
particles and rhPDGF-BB (1.0 mg/mL), covered
facially and lingually with an absorbable collagen
membrane. Clinical and histologic outcomes were
reported. At 6 months postoperatively, an increase in
REC was observed in all cases. Three of the four
defects remained as Class III, and only one defect
showed a positive response demonstrated by a con-
version to a Class II. Histologic evidence of partial
Avila-Ortiz, De Buitrago, Reddy
regeneration in all four sites was shown, but no
complete regeneration to the fornix of the furcation
was observed in any of the cases. No radiographic,
microbiologic, or patient-reported outcomes are re-
ported in this study.
Only one case report on the application of re-
generative therapies in the treatment of mandibular
Class III furcation defects was identified (see sup-
plementary Table 10 in online Journal of Peri-
odontology).202 This case report described the
treatment of a Class III furcation defect associated
with a pulpal lesion.202 The therapy consisted of
endodontic treatment, followed by an OFD and
grafting of the defect with a non-absorbable bio-
glass. The primary clinical outcome was the ab-
sence of suppuration on re-evaluation, whereas the
radiographic outcome of interest was changes in
bone levels (BLs). At the 6-month evaluation, ad-
equate healing in the absence of symptoms and
gain in radiographic BLs were observed. No mi-
crobiologic, histologic, or patient-reported outcomes
are reported in this report. This information can be
considered to be anecdotal.
Maxillary premolars presenting Class I, Class II,
or Class III furcation defects. Only one clinical trial
assessing the effectiveness of regenerative therapies
in the treatment of Class I or II furcation defects in
maxillary premolars was identified (see supplemen-
tary Table 11 in online Journal of Periodontology).79
In this study, nine patients presenting a total of 10
maxillary premolars with proximal Class I or Class II
defects were recruited. Four premolars were included
in the control group (OFD), and six were allocated
in the test group (OFD + ePTFE membrane). Three
premolars with Class II defects were included in the
test group, whereas only one premolar with this
characteristic was included in the control group.
Clinical (e.g., VPD and VAL) and radiographic (i.e.,
subtraction radiography analyses) outcomes were
reported. Very limited improvement was observed in
both groups for all the parameters analyzed. Among
the teeth treated in this study, only one premolar in
the test group showed signs of improvement. Fur-
thermore, in three experimental sites, there was more
bone loss at 6 months than at baseline.
FACTORS THAT MAY AFFECT REGENERATIVE
OUTCOMES IN FURCATION DEFECTS
It is extremely important to highlight that each clin-
ical scenario should be approached individually,
recognizing local and systemic variables that may
affect treatment planning and long-term success
after the indication of a particular therapy. Accu-
rate diagnosis, prognosis, and risk assessment of
periodontal pathologic conditions are fundamen-
tal aspects of periodontal therapy. Likewise, the
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Periodontal Regeneration: Furcation Defects
identification and understanding of factors that may
affect the course of treatment is of paramount im-
portance to achieve successful and predictable out-
comes. As illustrated by the selected literature,
periodontal regeneration in furcation defects is fea-
sible in certain clinical scenarios, particularly max-
illary facial and mandibular Class II defects. This has
also been histologically evidenced in several re-
ports.180,199,201,203,204 However, what are the factors
that may determine the success of a regenerative
technique in furcation defects? These factors can be
divided into two major groups: 1) systemic; and 2)
local anatomic.
Interestingly, among the different systemic factors
that may adversely affect regenerative therapy, such
as uncontrolled diabetes mellitus and conditions
affecting the immune system, only smoking has
been directly associated with detrimental effects in
the treatment of furcation defects by means of re-
generative therapy.48,98,130,165,211
Multiple local anatomic factors, such as location of
the affected site, features of the furcation entrance,
root trunk length, and local developmental abnor-
malities, may potentially affect the therapeutic op-
tions and also the success of the treatment.50 The
root complex of a multirooted tooth can be divided
in two sections: 1) the root trunk; and 2) the root
cone (s). The shorter the root trunk, the more sus-
ceptible a multirooted tooth is to develop a furcation
defect associated with the progression of periodontal
disease.212 Root trunk concavities are anatomic
features that may not only predispose the estab-
lishment and progression of periodontal disease but
may also detrimentally affect the outcomes of re-
generative therapy in mandibular Class II furcation
defects.31,127 Also, convergent root cones are more
difficult to regenerate, and, once the furcation is affected,
disease progression is favored.213 Root proximity is
also potentially detrimental for the outcomes of re-
generative therapy because it limits the access to the
defect preventing proper debridement, particularly in
mandibular molars.6,179 The predictive value of the
furcation entrance width and depth have also been
investigated. In mandibular Class II furcation defects,
the baseline HFD was positively correlated with VPD
reduction and gain in terms of VAL and HAL.138 Initial
vertical defect depth has been also indicated as
a predictor of regenerative outcomes in the treatment
of mandibular Class III furcation defects. In a study by
Mehlbauer et al.,109 it was observed that 74% of the
defects with a baseline vertical defect depth £4 mm
were closed at re-entry, whereas only 11% of those
with vertical openings >4 mm were closed. Also,
initial PD has been strongly correlated with VAL and
HAL gain, meaning that deeper PDs can be used as
predictors of positive outcomes.84 The position of the
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Volume 86 • Number 2 (Suppl.)
interproximal bone relative to the entrance of the
furcation is another factor that may play an important
role in the success of regenerative therapy. More
favorable outcomes are expected in sites in which the
interproximal bone height is coronal to the entrance
of the furcation defect compared with those in which
the interproximal bone is located at the same level or
even more apical.80,171 A thicker periodontal bio-
type over Class II furcation defects, defined as
a bucco-lingual gingival thickness >1 mm, has been
associated positively with minimized REC after GTR
therapy compared with sites presenting a thinner
biotype.34 Previous endodontic therapy and the
presence of cervical enamel projections on the af-
fected tooth, as well as non-absorbable membrane
exposure, do not seem to influence the outcomes of
regenerative therapy in mandibular Class II furcation
defects.52,174
CONCLUSIONS
After the analysis of the literature selected in this
review and considering the findings of previous
systematic reviews on this topic, it can be concluded
that the indication of regenerative approaches for the
treatment of furcation defects is predictable in certain
clinical scenarios, particularly in maxillary facial or
interproximal and mandibular facial or lingual Class II
furcation defects. The clinical evidence supporting
the indication of periodontal regenerative therapy in
the treatment of mandibular Class III defects is limited
to case reports. Regenerative therapy in maxillary
molars presenting Class III furcation defects and in
maxillary premolars affected by Class II or III furca-
tion defects is not predictable based on current
available evidence. Given the marked methodologic
heterogeneity and the wide variety of materials and
techniques applied in the selected studies, specific
guidelines for the development of clinical protocols
that may lead to successful and predictable out-
comes after the performance of periodontal re-
generative therapy for the treatment of different types
of furcation defects cannot be established. For the
same reasons, the conduction of a meta-analysis was
not viable. It is important to remark that, when in-
terpreting the results presented in the selected liter-
ature (see supplementary Tables 1-11 in online
Journal of Periodontology), readers should consider
the relatively low sample size in some of the studies
and make a careful distinction between clinical and
statistical significance.214,215
Considering the gaps of knowledge identified in
this review, future research efforts should be di-
rected primarily toward the conduction of clinical
trials that compare non-regenerative surgical in-
terventions with novel regenerative approaches that
may overcome the limitations of previously applied
J Periodontol • February 2015 (Suppl.)
therapies for the treatment of clinical scenarios his-
torically associated with unpredictable outcomes (i.e.,
proximal Class II defects and Class III defects). These
novel approaches should include, but are not neces-
sarily limited to, the use of tissue engineering-based
approaches consisting of the application of biologic
agents, growth factors, scaffolds, pluripotential cells or
a combination of them, and laser therapy. To date,
there is only one study on the application of laser-
assisted regenerative therapy for the treatment of
furcation defects, which reported promising clinical
outcomes.197 Investigators should also focus on the
understanding of the influence that insufficiently
studied local, technical, and systemic factors, such
as metabolic disorders, have on the outcomes of
regenerative therapy. These future studies should
also have long-term follow-ups, ideally >5 years
after baseline, and should place more emphasis on
histologic and patient-reported outcomes. These
methodologic additions are expected to provide the
scientific community with critical information to
better understand the influence that periodontal re-
generative therapies have on the quality of life of
patients receiving regenerative therapies, which will
be of great value to develop cost-effective and pre-
dictable clinical protocols.
ACKNOWLEDGMENTS
The authors thank Ms. Patricia Conrad, Educational
Media Unit at the University of Iowa College of Den-
tistry, Iowa City, Iowa, for her assistance in the creation
of the original artwork. Dr. Avila-Ortiz thanks the Amer-
ican Academy of Periodontology Foundation for the
support provided to pursue an academic career in peri-
odontics. Dr. Avila-Ortiz has received research funding
from Osteogenics Biomedical (Lubbock, Texas), Geist-
lich Pharma (Wolhusen, Switzerland), DENTSPLY
(York, Pennsylvania), and BioHorizons (Birmingham,
Alabama) and lecture honoraria from Laboratorios IN-
IBSA (Barcelona, Spain). Dr. Reddy has received grant
support and other funding through his institution, the
University of Alabama at Birmingham; from BioD-
Logics (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 Insti-
tutes 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, Colgate-Palmolive, and the
Osteology Foundation.
Avila-Ortiz, De Buitrago, Reddy
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Correspondence: Dr. Gustavo Avila-Ortiz, Department
of Periodontics, University of Iowa, 801 Newton Rd.,
Iowa City, IA 52242. E-mail: gustavo-avila@uiowa.edu.
Submitted November 14, 2013; accepted for publication
April 20, 2014.