J Clin Periodontol 2012; 39 (Suppl. 12): 202206 doi: 10.1111/j.1600-051X.2011.01837.

Clinical research on peri-implant Mariano Sanz1,*, Iain L. Chapple2

and on behalf of Working Group 4 of
the VIII European Workshop on

diseases: consensus report of Periodontology*

1
University Complutense of Madrid
Periodontology, Madrid, Spain; 2Periodontal

Working Group 4 Research Group, The University of

Birmingham, Birmingham, United Kingdom

Sanz M, Chapple IL, on behalf of Working Group 4 of the VIII European

Workshop on Periodontology. Clinical research on peri-implant diseases: consensus
report of Working Group 4. J Clin Periodontol 2012; 39 (Suppl. 12): 202206. doi:
10.1111/j.1600-051X.2011.01837.x.

Abstract:
Background: Two systematic reviews have evaluated the quality of research and
reporting of observational studies investigating the prevalence of, the incidence of
and the risk factors for peri-implant diseases and of experimental clinical studies
evaluating the ecacy of preventive and therapeutic interventions.
Materials and Methods: For the improvement of the quality of reporting for both
observational and experimental studies, the STROBE and the Modied
CONSORT recommendations were encouraged.
Results: To improve the quality of research in peri-implant diseases, the following Key words: incidence; intervention;
were recommended: the use of unequivocal case denitions; the expression of out- peri-implant diseases; peri-implant health;
peri-implant mucositis; peri-implantitis;
comes at the subject rather than the implant level; the implementation of study
prevalence; prevention; risk factors
validation tools; the reporting of potential sources of bias; and the use of appro-
priate statistical methods. Accepted for publication 26 November 2011

Conflict of interest and source of funding statement

The authors declare that they have no conict of interests. This workshop was
nancially supported by the European Federation of Periodontology and by unrest-
ricted grants from Astra, Nobel Biocare and Straumann.

Working Group 4:
Mariano Sanz,
Iain Chapple,
Jan Derks,
E. Figuero,
Filippo Grazianni,
Lisa Heitz-Mayeld,
David Herrera,
Ann-Marie Jansaker,
Soren Jepsen,
Bjorn Klinge,
Bruno Loos,
Andrea Mombelli,
Panos Papapanou,
Ioannis Polyzois,
Stefan Renvert,
Giovanni Salvi,

Industry representation:
Pascal Kunz,
Anna-Karin Lundgren,
Rene Willi.

202 2012 John Wiley & Sons A/S

 Clinical research in peri-implant diseases 203

Conclusions: In observational studies, case denitions for peri-implantitis were

agreed. For risk factor determination, the progressive use of cross-sectional and
casecontrol studies (univariate analyses), to prospective cohorts (multilevel mod-
elling for confounding), and ultimately to intervention studies were recommended.
For preventive and interventional studies of peri-implant disease management,
parallel arm RCTs of at least 6-months were encouraged. For studies of non-
surgical and surgical management of peri-implantitis, the use of a composite
therapeutic end point was advocated. The development of standard control
therapies was deemed essential.

The selected studies investigating the level of crestal bone, presence of

Introduction
The remit of this working group was
to provide answers to key aspects of
clinical research into peri-implant
diseases focusing on aspects of study
design, reporting and outcome mea-
surements.
Two reviews had evaluated the
quality of research and the quality
of reporting of observational studies
investigating the prevalence of, the
incidence of and the risk factors for
peri-implant diseases (Tomasi &
Derks 2012), as well as those experi-
mental clinical studies evaluating the
ecacy of preventive and therapeutic
interventions (Graziani et al. 2012)
in a systematic manner.
Quality of Reporting, Case
Definitions and Methods to Study
Incidence of, Prevalence of and Risk
Factors for Peri-Implant Diseases
The systematic review evaluating the
quality of reporting of the observa-
tional studies investigating the inci-
dence of, prevalence of and risk
factors for peri-implant diseases
(Tomasi & Derks 2012) highlighted
that many studies have solely
reported implant-based data analysis
or have not provided a clear deni-
tion of the peri-implant diseases
being studied.
Another important issue empha-
sized in the review was the dierent
criteria used for dening a case in
studies investigating the prevalence
of peri-implant diseases. Whilst stud-
ies performed since the previous
European Workshops have used the
denitions developed in those con-
sensus meetings (Lang & Berglundh
2011), there are still dierences in
the thresholds employed for radio-
graphic bone loss used to dene
peri-implantitis and the reference
time point from which this bone loss
has occurred.
2012 John Wiley & Sons A/S
the prevalence of peri-implant dis-
eases have used cross-sectional study
designs and convenience samples,
mostly of limited size, with clinical
and radiological outcomes as the
basis for dening health, versus peri-
implant mucositis and peri-implanti-
tis. These convenience samples may
not be representative of the target
population.
When analysing the quality of
reporting in the selected studies, the
STROBE recommendations (Van-
denbroucke et al. 2007a, b, c) have
been utilized. Although most of the
studies lack reporting of the possible
sources of bias and few have evalu-
ated aspects of internal validity,
approximately 6070% of the recom-
mendations were fullled.
From the outset, the group
agreed and acknowledged the strat-
egy of the authors to focus on inves-
tigations assessing prevalence of
those peri-implant diseases based at
the subject level. The group consid-
ered that the impact of peri-implant
diseases upon individuals was the
outcome of interest, rather than the
impact upon individual implants.
When discussing the dierent case
denitions employed in the studies
evaluating prevalence and incidence
of peri-implant diseases, the group
agreed that the denitions estab-
lished in the previous EWP consen-
sus workshops published in 2008
(Lindhe & Meyle 2008) and 2011
(Lang & Berglundh 2011) should be
adopted. This consensus attempts to
further clarify some key aspects that
are relevant to the conduct of obser-
vational studies to improve the
methodological quality and reporting
standards of clinical research in peri-
implant diseases.
For dening a case as peri-implan-
titis, it was agreed that the compo-
nents described in previous consensus
reports must be present: changes in
bleeding on probing and/or suppura-
tion; with or without concomitant
deepening of peri-implant pockets
(Lang & Berglundh 2011). It was
strongly recommended that for inves-
tigations assessing the prevalence and
incidence of peri-implant diseases, all
studies must be underpinned by basic
quality assurance procedures includ-
ing internal validation of examiner
reproducibility and the use of mea-
surement instruments aimed at reduc-
ing their inherent variability. It is
recommended that long-cone parallel
radiographic projection techniques
were utilized to assess the crestal bone
changes. Details of the probing proto-
col utilized should also be described.
In this context, the group agreed
that dierent approaches should be
used when dealing with studies of
disease prevalence and incidence.
Studies on disease prevalence
For disease prevalence, it was
accepted that individuals presenting
with peri-implant diseases might not
have baseline clinical or radiological
measures available to benchmark
current ndings, and therefore more
pragmatic case denitions should be
developed to serve as the basis for
diagnosis of peri-implantitis and on
clinical decision making for thera-
peutic purposes . Here, the focus is
specicity of diagnosis rather than
sensitivity, accepting the possibility
of false negative diagnoses. In the
absence of previous radiographic
records, a threshold vertical dis-
tance of 2 mm from the expected
marginal bone level following
remodelling post-implant placement
is recommended, provided peri-
implant inammation is evident. If
previous radiographs are available,
a more sensitive threshold for mea-
surable bone loss can be used
depending on the reproducibility of
204 Sanz et al.
the radiological assessment method
employed.
Studies on peri-implantitis incidence
For prospective studies evaluating
the incidence and or progression/
recurrence of peri-implantitis, base-
line clinical measures and radio-
graphs are essential. Since these
studies must be planned thoroughly
and ethical approval must be
obtained, baseline clinical and radio-
logical data should be established
once the remodelling phase post-
implant placement has occurred. In
this manner, in the presence of
inammation, any detectable bone
loss beyond the inherent variability
of the radiological measurement
error, should be considered as loss
of supporting bone and hence, used
in the case denition. Such reference
data permits more sensitive case de-
nitions to be developed, accounting
for measurement errors, but provid-
ing higher sensitivity and accepting
the potential for some false positive
assignments of peri-implant disease.
For these incidence studies, a thresh-
old of detectable bone loss of 23
times the SD of the measurement
error is recommended (1.01.5 mm).
Studies on risk factors for peri-implant
diseases
Studies addressing risk factors in
peri-implant diseases are in their
infancy. Traditionally, risk factors
are identied on the basis of a multi-
step process including:
Identication of putative risk fac-
tors using cross-sectional or case-
control studies and univariate
analyses, followed by multi-variate
analyses aimed at identifying
potential confounding factors
Studies validating these putative
factors, which employ a prospec-
tive cohort design, ideally con-
rmed in dierent populations
In the case of modiable true risk
factors, intervention studies dem-
onstrating lower incidence of dis-
ease following targeted control of
the respective factors
The currently available literature
primarily consists of cross-sectional
and casecontrol studies, which are
limited in their generalizability.
Based upon the approach taken in
this systematic review (Tomasi &
Derks 2012), four prospective cohort
studies exist with limited sample
sizes, and based upon convenience,
samples rather than broader sam-
pling of the population exist . There
is heterogeneity in the risk indicators
investigated across the broad catego-
ries of host-derived, lifestyle, envi-
ronmental and local factors. Given
the limited sample sizes investigated
so far, it is not possible to assess
with precision the interactions
between the dierent exposures of
interest.
Recommendations for future research
Based upon the available evidence,
the group recommends that addi-
tional and adequately powered
research should be conducted to val-
idate the most plausible putative risk
factors for the onset and progression
of peri-implant diseases, including:
History of treated and/or current
periodontitis
Oral hygiene
Smoking and other subject-related
factors
Local factors such as malposition-
ing of implants (within the basal
bone, inter-implant, implant-
tooth), lack of cleansability of the
reconstruction, excess cement and
implant surface characteristics
To establish valid and reliable sta-
tistics on the prevalence and incidence
of peri-implant diseases, it is recom-
mended that national/regional data-
bases of patients receiving implant
therapy be established. These should
include both baseline and annual fol-
low-up assessments of implant status
and potential exposures.
These registries will facilitate the
conduct of future studies of risk fac-
tor assessment that are:
Adequately powered and
adjusted
Representative of the population
at large
Of sucient duration
Inclusive of dierent settings
(University, Specialist Practice,
General Practice)
In the absence of such databases,
it is recommended that multicentre
studies be conducted to enhance the
generalizability (size, power) of study
outcomes.
Study quality will be improved
by:
Establishing unequivocal case de-
nitions
Involving calibrated examiners
Careful assessment and reporting
of exposures (e.g. oral hygiene sta-
tus, periodontal status and smok-
ing history)
Selection of unbiased samples of
sucient size
Provisions to account for loss to
follow-up
Appropriate statistical analyses
Employing validated tools such
as the STROBE guidelines will
attain improvements in the quality
of reporting.
Quality of Reporting Outcome
Measurements and Methods to Study
the Ecacy of Preventive and
Therapeutic Approaches to Peri-
Implant Diseases
The systematic review evaluating the
ecacy of preventive and therapeutic
approaches to peri-implant diseases
(Graziani et al. 2012) focussed upon
the selection of randomized clinical
trials (RCTs) and controlled clinical
trials (CCTs) assessing the ecacy of
preventive measures to preserve
peri-implant health and therapeutic
interventions aimed at treating per-
implant mucositis and peri-implanti-
tis either non-surgically or surgically.
Preventive studies of peri-implant
diseases
There was a notable paucity of clini-
cal trials addressing the ecacy of
preventive interventions. From 155
studies identied as potentially fulll-
ing the review criteria, only seven
were selected. Studies were not con-
sidered either because their experi-
mental design was not an RCT or a
CCT, or because the study evaluation
time was too short. The selected stud-
ies utilized dierent experimental
designs (parallel, cross-over and split
mouth) and usually employed small
sample sizes and short evaluation
times. The interventions assessed
included the use of adjunctive anti-
microbials or specic preventive
2012 John Wiley & Sons A/S

interventions aimed at plaque control
around the implant supported resto-
rations, compared with the patients
self-performed plaque control and
with professional supportive therapy.
Reported outcomes employed to
evaluate the ecacy of the tested
interventions have mainly been the
use of bleeding and plaque indices,
although in some studies, additional
clinical (changes in PPD) and micro-
biological outcomes were used. The
studies demonstrated moderate
adherence to modied CONSORT
recommendations (<50% of the
items) and lacked reporting of poten-
tial sources of bias.
A signicant problem was identi-
ed with regard to the lack of a
standard preventive measure with
demonstrated ecacy to preserve
peri-implant health, which could be
used as a standard control treatment
in future intervention trials. It is rec-
ommended that with respect to
experimental design, the 6-month
parallel arm RCT should be
employed; comparing the tested
preventive interventions with a
combination of the patients routine
self-performed plaque control mea-
sures and regular professionally
delivered supportive therapy (oral
prophylaxis). The objective of
therapy should be the absence of
mucosal inammation around the
functioning dental implants, and
hence the primary outcomes should
be the evaluation of the changes in
mucosal inammation (e.g. the mod-
ied bleeding index) and the absence
of bleeding upon probing.
Treatment of peri-implant mucositis
There were only six parallel arm
RCTs evaluating the adjunctive
eect of antimicrobial compounds
(Chlorhexidine, Triclosan and Essen-
tial Oils) in the treatment of peri-
implant mucositis. These studies
have used short evaluation times (3
8 months) and share the problems of
small sample sizes, the lack of a
clear denition of the problem inves-
tigated (peri-implant mucositis) and
incomplete registration of periodon-
tal status in the studied samples. As
outcome measures, the reported
studies evaluated the inammatory
status of the peri-implant mucosa
(BOP), probing depths and plaque
indices. Three studies assessed
2012 John Wiley & Sons A/S
Clinical research in peri-implant diseases
microbiological outcomes and one
reported the percentage of lesions
resolved. When analysing the quality
of reporting and performance in the
selected studies, there was between
17% and 90% adherence to the
modied CONSORT recommenda-
tions.
The group agreed that the paral-
lel arm RCT of at least 6-months
duration (and including 3-month
examinations) should be used for
evaluating therapies to treat peri-
implant mucositis. The endpoint of
therapy should be the resolution of
peri-implant mucosal inammation
(frequency distribution of resolved
lesions) as determined by the absence
of bleeding upon probing. As sec-
ondary outcomes, probing pocket
depth reductions and outcomes
assessing hostparasite interactions
(presence of inammatory biomar-
kers in peri-implant uid and/or
microbiological assessment of sub-
gingival plaque samples) may be
employed. Information on the sub-
jects characteristics (e.g. smoking),
the impact of the periodontal status
and the status of the reconstruction
(access for plaque control, etc.)
should also be reported.
Non-surgical treatment of peri-implantitis
Six parallel arm RCTs and one split-
mouth study have evaluated the e-
cacy of non-surgical therapies for
the treatment of peri-implantitis.
These intervention studies have used
dierent case denitions for peri-im-
plantitis and have small sample sizes,
along with short evaluation periods
(4.5 months; only one 12-month
study) and a lack of a clear descrip-
tion of the periodontal status of the
sample studied. There was no
standard control treatment in these
studies; however, mechanical
debridement was included in all
treatment arms. The tested interven-
tions were either the adjunctive use
of local antibiotics or alternative
implant surface debridement meth-
ods (laser, ultrasonic or air abrasive
devices). The outcomes utilized in
these studies were reductions in
PPD, reductions in the sites bleeding
(BOP) and reductions in clinical
attachment levels (CAL), and three
studies also evaluated microbiologi-
cal and radiological outcomes and
one reported suppuration. A com-
205
mon nding in the reported studies
was reductions in PPDs and BOP
following the test and control inter-
ventions; however, it remains unclear
as to how frequently the end point
of therapy (resolution of inamma-
tion and shallow probing depths)
was met, as it was only reported in
one study.
The group agreed that the lack of
a standard control mode of non-sur-
gical therapy to treat peri-implantitis
was problematic. At the present time,
there are no data indicating that peri-
implantitis lesion severity can be the
basis for recommending non-surgical
or surgical therapy. As an RCT eval-
uating non-surgical therapy versus an
untreated control arm is unethical,
case series and prospective cohort
studies may be used to better dene
the eect of non-surgical therapy
alone. The parallel arm RCT with a
mechanical treatment control arm
should be utilized to evaluate adjunc-
tive/alternative therapies. These stud-
ies should include both short-term (1
3 months) and longer-term evalua-
tion times (6 and 12-months). At 3-,
6- and 12-months, probing pocket
depth, bleeding on probing and sup-
puration should be assessed. In addi-
tion, the maintenance of bone levels
should be assessed radiologically at
12-months. It is recommended that a
composite outcome of disease resolu-
tion is included (absence of deep
probing pocket depths with bleeding
and suppuration). As secondary out-
come measures, inammatory bio-
markers in peri-implant uid and/or
microbiological assessment of sub-
mucosal plaque samples may be used.
Information on the periodontal status
of the remaining dentition and on
patient reported outcomes (smoking,
discomfort, aesthetic consequences,
etc.) should be reported. Multi-centre
approaches are advocated to achieve
suciently powered studies.
Surgical treatment of peri-implantitis
There are three parallel arm RCTs
and three CCTs that have evaluated
the ecacy of surgical therapies for
the treatment of peri-implantitis.
These intervention studies have used
dierent case denitions for peri-im-
plantitis, and have in common, small
sample sizes and the lack of a clear
description of the periodontal and
smoking status of studied sample.
206 Sanz et al.
There was no standard control inter-
vention in these studies; however,
access ap, including debridement/
degranulation of the lesion and
decontamination of the implant sur-
face was included in all treatment
arms, with some studies adding sys-
temic antibiotics and others adding
only adjunctive antimicrobials
(Chlorhexidine). As interventions,
some had employed dierent modes
of decontaminating the implant sur-
face with laser devices, air abrasives
and re-shaping the titanium surface,
whereas other therapies have
attempted to reduce the intra-bony
defect, either by resection or by
treating the defect with biomaterials
and/or membranes. The paucity of
published clinical trials, the limited
sample sizes (n = 1738) and the het-
erogeneity of treatments tested pre-
vent the drawing of denitive
conclusions on the ecacy of these
interventions. The evaluation of
reporting according to the modied
CONSORT recommendations
resulted in <60% adherence in four
of the studies.
It is recommended that a stan-
dard mode of surgical therapy is
identied for the treatment of peri-
implantitis is identied. This therapy
should include a clear surgical
design, a proven method of decon-
taminating the implant surface and
an appropriate means of infection
control. From the six selected clini-
cal trials, only two have used
adjunctive systemic antimicrobials as
part of the surgical therapy regime,
whereas the other four have only
used adjunctive antiseptics. There is
therefore a lack of clear scientic
evidence whether the adjunctive use
of systemic antimicrobials might be
recommended as part of the stan-
dard mode of therapy. An RCT test-
ing this hypothesis is needed.
There is a consensus that for the
evaluation of dierent surgical thera-
pies, the parallel arm RCT should be
used, with assessment of the end
points of the therapy at least at 6
and 12 months.
It is recommended that a com-
posite outcome of disease resolution
is included (absence of deep probing
pocket depths with bleeding and
suppuration and no additional bone
loss).
As principal outcome measure-
ments, resolution of mucosal inam-
mation, reduction in probing pocket
depths and changes in the bone lev-
els should be employed. As second-
ary outcomes, levels of inammatory
biomarkers in peri-implant uid and/
or microbiological assessment of
sub-marginal plaque samples may be
used. Information on the periodontal
status of the studied samples and on
patient reported outcomes (discom-
fort, aesthetic consequences, etc.)
should be reported.
It is strongly recommended that
authors adhere to the reporting
guidelines, as detailed in the system-
atic review (Graziani et al. 2012).
Multi-centre approaches are encour-
aged to achieve suciently powered
studies and representative popula-
tions of diverse defect morphologies
and severities.
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Address:
Mariano Sanz
Universidad Complutense de Madrid
Facultad de Odontologia
Plaza Ramon y Cajal
E-28040 Madrid
Spain
E-mail: marianosanz@odon.ucm.es
2012 John Wiley & Sons A/S