Supplementary Online Appendix:
This online appendix included: a detailed description of literature search strategy, the assessment of
risk of bias, supplementary tables and figures.
Literature search strategy
PubMed search
#1 ("bone transplantation"[MeSH Terms] OR ("bone"[All Fields] AND "transplantation"[All
Fields]) OR "bone transplantation"[All Fields]) OR ("bone transplantation"[MeSH Terms] OR
("bone"[All Fields] AND "transplantation"[All Fields]) OR "bone transplantation"[All Fields] OR
("bone"[All Fields] AND "graft"[All Fields]) OR "bone graft"[All Fields]) OR ("bone
substitutes"[MeSH Terms] OR ("bone"[All Fields] AND "substitutes"[All Fields]) OR "bone
substitutes"[All Fields])
#2 (("dental enamel"[MeSH Terms] OR ("dental"[All Fields] AND "enamel"[All Fields]) OR
"dental enamel"[All Fields] OR "enamel"[All Fields]) AND ("proteins"[MeSH Terms] OR
"proteins"[All Fields])) OR (("dental enamel"[MeSH Terms] OR ("dental"[All Fields] AND
"enamel"[All Fields]) OR "dental enamel"[All Fields] OR "enamel"[All Fields]) AND
derivative[All Fields] AND ("proteins"[MeSH Terms] OR "proteins"[All Fields]))
#3 (Flap[All Fields] AND ("surgical procedures, operative"[MeSH Terms] OR ("surgical"[All
Fields] AND "procedures"[All Fields] AND "operative"[All Fields]) OR "operative surgical
procedures"[All Fields] OR "operation"[All Fields])) OR (open[All Fields] AND ("surgical
flaps"[MeSH Terms] OR ("surgical"[All Fields] AND "flaps"[All Fields]) OR "surgical flaps"[All
Fields] OR "flap"[All Fields]) AND ("debridement"[MeSH Terms] OR "debridement"[All Fields]))
OR (periodontal[All Fields] AND ("surgical flaps"[MeSH Terms] OR ("surgical"[All Fields] AND
"flaps"[All Fields]) OR "surgical flaps"[All Fields] OR "flap"[All Fields])) OR (Widman[All
Fields] AND ("surgical flaps"[MeSH Terms] OR ("surgical"[All Fields] AND "flaps"[All Fields])
1
OR "surgical flaps"[All Fields] OR "flap"[All Fields])) OR (modified[All Fields] AND
Widman[All Fields] AND ("surgical flaps"[MeSH Terms] OR ("surgical"[All Fields] AND
"flaps"[All Fields]) OR "surgical flaps"[All Fields] OR "flap"[All Fields]))
#4 "intercellular signaling peptides and proteins"[MeSH Terms] OR ("intercellular"[All Fields]
AND "signaling"[All Fields] AND "peptides"[All Fields] AND "proteins"[All Fields]) OR
"intercellular signaling peptides and proteins"[All Fields] OR ("growth"[All Fields] AND
"factors"[All Fields]) OR "growth factors"[All Fields]
#5 ("guided tissue regeneration"[MeSH Terms] OR ("guided"[All Fields] AND "tissue"[All Fields]
AND "regeneration"[All Fields]) OR "guided tissue regeneration"[All Fields]) OR GTR[All Fields]
#6 ((((#1) OR #2) OR #3) OR #4) OR #5
#7 "alveolar bone loss"[MeSH Terms] OR ("alveolar"[All Fields] AND "bone"[All Fields] AND
"loss"[All Fields]) OR "alveolar bone loss"[All Fields]
#8 (Intra[All Fields] AND bony[All Fields] AND defect[All Fields]) OR (Intrabony[All Fields]
AND defect[All Fields]) OR (Infrabony[All Fields] AND defect[All Fields]) OR (infra-bony[All
Fields] AND ("abnormalities"[Subheading] OR "abnormalities"[All Fields] OR "defects"[All
Fields]))
#9 (#7) OR #8
#10 "bone regeneration"[MeSH Terms] OR ("bone"[All Fields] AND "regeneration"[All Fields])
OR "bone regeneration"[All Fields]
#11 (Periodontal[All Fields] AND ("regeneration"[MeSH Terms] OR "regeneration"[All Fields]))
OR periodontal-regeneration[All Fields]
#12 (#10) OR #11
#13 Randomized Controlled Trials AND humans
#14 (#6) OR #9
#15 (#12) AND #14
#16 (#13) AND #15
2
EMBASE search
#1 bone transplantation OR bone graft OR bone substitutes
#2 enamel derivative protein OR enamel matrix derivative OR Endogain
#3 surgical flaps OR surgical procedures OR operative surgical procedures OR open flap
debridement OR periodontal surgical flaps OR Widman flap OR modified Widman flap
#4 growth factors OR intercellular signaling peptides and proteins
#5 guided tissue regeneration OR GTR
#6 ((((#1) OR #2) OR #3) OR #4) OR #5
#7 alveolar bone loss
#8 intrabony defect OR infrabony defect OR infra-bony
#9 (#7) OR #8
#10 bone regeneration
#11 periodontal regeneration
#12 (#10) OR #11
#13 randomized controlled trials AND humans
#14 (#6) OR #9
#15 (#12) AND #14
#16 (#13) AND #15
Assessment of risk of bias
The risk of bias of the studies was assessed by focusing on the points described at the Cochrane
Collaboration’s tool for assessing risk of bias (Higgins & Green 2008). Six main domains were
assessed to determine the risk of bias of included studies: adequate sequence generation, allocation
concealment, blinding, incomplete outcome data addressed, and free of selective reporting. Each
domain included a specific entry that was described in a “risk of bias” table. Then, we assigned a
3
judgement relating to the risk of bias for each entry, by answering a pre-specified question about the
adequacy of the study in relation to the entry (Higgins & Green 2008). Answer YES (criterion was
met) indicates low risk of bias, NO (criterion was not met) indicates high risk of bias, and
UNCLEAR (insufficient information to permit judgement, for example the topic in question was
partially or not reported) indicates unclear or unknown risk of bias. In the overall study assessment,
the risk of bias was determined using the following criteria: (a) low risk of bias – if all entries were
answered YES; (b) unclear risk of bias – if one or more entries were answered UNCLEAR; and (c)
high risk of bias - if one or more entries were answered NO.
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SUPPLEMENTARY TABLES
Supplementary Table 1: Quality Assessment of included RCTs for network meta-analysis
Study
Blumenthal 1990
Bokan 2006
Chambrone 2010
Christau 2006
Chung 1990
Cortellini 1995
Cortellini 1996
Cortellini 1998
Cortellini 2001
Cortellini &
Tonetti 2011
DiBattista 1995
Crea 2008
Dori 2007 JCP
Dori 2007 JOP
Dori 2008 JCP
Dori 2008 JOP
Fickl 2009
Francetti 2004
Francetti 2005
Froum 2001
Grusovin 2009
Guida 2007
Heijl 1997
Linares 2006Җ
Loos 2002
Mayfield 1998
Mellado 1995
Meyle 2011
Minabe 2002
Mora 1996
Okuda 2000
Paolantonio 2008
Pontoriero 1999
Pritlove-Carson
1995
Rakga-Kruger
2000
Rosing 2005
Sanz 2004
Sculean 2001
Sculean 2003
Sculean 2005
GTR
Sculean 2005
EMD
Siciliano 2011
Silvestri 2000
Silvestri 2003
Sipos 2005
Adequate
sequence
generation?
Unclear
Yes
Yes
Yes
Unclear
Yes
Yes
Yes
Yes
Yes
Allocation
concealment?
Blinding?
Unclear
Yes
Yes
Yes
Unclear
Yes
Yes
Unclear
Unclear
Unclear
Incomplete
outcome data
addressed?
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Free of
selective
reporting?
Yes
Yes¶
Yes
Yes
Yes@
Yes
Yes
Yes
Yes
Yes
Unclear
Unclear
No
Yes
Unclear
Unclear
Unclear
Unclear*
Yes
Yes
Unclear
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Unclear
Yes
Unclear
Yes
Unclear
Yes
Yes
Unclear
Unclear
Yes
Yes
Unclear
Yes
Risk of
bias
Unclear
Unclear
High
Low
Unclear
Unclear
Unclear
Unclear
Unclear
Unclear
Unclear
Unclear*
Unclear
Unclear
Unclear
Unclear
No
Unclear
Yes
Unclear
Yes
Unclear
Unclear*
Unclear
Unclear*
Unclear
Unclear
Unclear*
Unclear
Unclear
No§
Unclear
Unclear
No
Unclear
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
Unclear
Yes
Yes
Unclear
Yes
Yes&
Unclear
Unclear
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Unclear¤
Yes
Yes
Yes=
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes#
Yes
Yes
Yes=
Yes
Yes
Yes
Yes
Yes%
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Unclear
Unclear
Unclear
Unclear
Unclear
Unclear
High
Unclear
Low
Unclear
Low
High
Unclear
Unclear
Unclear
Unclear
Unclear
Unclear
Unclear
Unclear
High
Unclear
Unclear
High
Unclear
Unclear
Unclear
Yes
Yes
Unclear
Yes
Yes
Yes
Unclear
Yes
No
Unclear
No
Unclear
Unclear
Yes
No
Yes
Unclearµ
Yes
Yes
Unclear°
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
High
High
High
Unclear
Unclear
Yes
Unclear
Unclearµ
Yes
Yes
Unclear
Unclear
Unclear
Yes
Yes
Unclear
Unclear
Unclear
Unclear
Yes
Unclear
Unclear
Yes
Yes
Yes
Yes=
Yes^
Yes
Yes
Yes
Yes
Unclear
Unclear
Unclear
Unclear
5
Stavropoulos
2003
Tonetti 1998
Tonetti 2002
Tonetti 2004
Trejo 2000
Yilmaz 2010
Zucchelli 2002
Zucchelli 2003
Yes
Unclear*
Yes
Yes=
Yes
Unclear
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Unclear*
Yes
Yes
Unclear*
No
Unclear
Unclear
Unclear
No
No
Yes
Yes
Yes
Unclear
Yes=
Yes
Yes=
Yes=
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes#
Unclear
High
High
Unclear
High
Unclear
Unclear
*: authors reported sealed envelopes without reporting whether they were opaque; $: outcome measures are not clearly
reported in the material and methods section; ¤: it is not clear reported in the results section whether there was drop
outs; #: Full mouth plaque score (FMPS) and full mouth bleeding score (FMBS) were not reported in the results, but it
is unlikely that the lack of these outcomes will generate selective reporting; ¶: Full mouth plaque score (FMPS) was not
reported in the results, but it is unlikely that the lack of this outcome will generate selective reporting; %: bleeding on
probing (BOP) reported in the methods, but no in results, but it´s unlikely that the lack of this outcome will generate
selective reporting; @: bleeding index (BI) reported in the methods, but no in results, but it´s unlikely that the lack of
this outcome will generate selective reporting; §: other explicitly unconcealed procedure; &: only examination of defect
bone level was not blinded; “: only radiographical measurements were blinded; °: authors did not report the reasons for
drop out of 5 patients; µ: authors reported that the examiner and operator were not the same, without reporting whether
the examiners were blinded; =: authors reported reasons for drop out and the drop outs were less than 5% of the sample;
^: reasons for drop out explained (14 % of the sample left the study); Җ: This paper reports radiographic data and it
shares the same cohort of patients with other study (Tonetti 2004) that reports clinical data.
6