Stefan Renvert Risk indicators for peri-implantitis.

Marc Quirynen
A narrative review

Authors affiliations: Key words: biofilm, etiology, excess cement, genotype, microbiology, oral hygiene, partial
Stefan Renvert, Department of Oral Health edentulism, peri-implantitis, periodontitis, risk indicators, smoking, supportive periodontal
Sciences, Kristianstad University, Kristianstad,
Sweden therapy
Stefan Renvert, School of Dental Sciences, Trinity
College, Dublin, Ireland
Stefan Renvert, Blekinge Institute of Technology, Abstract
Karlskrona, Sweden Aim: To examine the existing evidence in identifying risk indicators in the etiology of peri-
Marc Quirynen, Department of Oral Health implantitis.
Sciences, Katholieke Universiteit Leuven,
University Hospitals Leuven, Leuven, Belgium Material and methods: A literature search was performed in MEDLINE via PubMed database of the
US National Library of Medicine, for articles published until October 2014 using Medical Subject
Corresponding author: Heading search terms + free text terms and in different combinations.
Stefan Renvert
Kristianstad University, 291 88 Kristianstad, Results: The microbiota associated with peri-implantitis is complex, demonstrating differences and
Sweden similarities to the one seen at periodontitis sites. Plaque accumulation at dental implants triggers
Tel.: +46 44 204090
the inflammatory response leading to peri-implant mucositis/peri-implantitis. Individuals with a
Fax: +46 44 204018
e-mail: stefan.renvert@hkr.se history of periodontal disease and smokers have an increased risk of developing peri-implantitis.
There is some evidence to support the role of genetic polymorphism, diabetes, and excess cement
as risk indicators for the development of peri-implantitis. There is also evidence to support that
individuals on regular maintenance are less likely to develop peri-implantitis and that successful
treatment of periodontitis prior to implant placement lowers the risk of peri-implantitis.
Conclusions: Plaque accumulation at implants will result in the development of an inflammation
at implants. A history of periodontal disease, smoking, excess cement, and lack of supportive
therapy should be considered as risk indicators for the development of peri-implantitis.

Over the last decades, the use of dental
implants has become a common way of
replacing teeth. For the healthy patient,
survival rates for oral implants have been
reported to be 91.5%, even after 15 years fol-
low-up, at least if the implants are placed
under favorable conditions (Dierens et al.
2012). Also, the amount of marginal bone
loss is limited in most patients as confirmed
by a large-scale meta-analysis on implants
5 years in function (Laurell & Lundgren
2011). Varying rates of technical, biological,
and esthetic complications can occur (Roc-
cuzzo et al. 2010, 2012, 2014; Jung et al.
2012; Pjetursson et al. 2012a; Romeo & Stor-
elli 2012). Peri-implantitis is clinically
defined by the presence of redness and swell-
ing of the mucosa, bleeding and/or suppura-
tion on probing, deepening of the pockets
adjacent to the dental implants, and loss of
the implant-supporting bone (Lindhe & Mey-
le 2008). Peri-implantitis has been reported to
Date: occur in the range of 1.4% to 53.5% (Buser
Accepted 12 May 2015
et al. 2012; Fardal & Grytten 2013). The large
To cite this article:
Renvert S, Quirynen M. Risk indicators for peri-implantitis. differences in the reported prevalence rates
A narrative review. may be explained by differences in the defini-
Clin. Oral Impl. Res. 26 (Suppl. 11), 2015, 1544
doi: 10.1111/clr.12636 tion of peri-implantitis, the inclusion of
convenience samples, and the prevalence of
maintenance care. Following a consensus
conference, it was stated that the prevalence
of peri-implantitis over a 510 year period
following implant placement has been
reported to be in the order of 10% of
implants and 20% of patients (Klinge et al.
2012) and in a recent meta-analysis with data
from nine studies and a total of 1497 partici-
pants, the frequency of peri-implantitis was
reported to be 18.8% on a subject level and
9.6% on an implant level (Atieh et al. 2013).
To obtain long-term success of dental
implant therapy, it is essential that the
patient can maintain healthy peri-implant
tissues. If microorganisms are allowed to
develop pathogenic complexes around the
implants, inflammation will occur (Pontori-
ero et al. 1994). When healthy dentate indi-
viduals restored with dental implants
underwent an experimental undisturbed pla-
que accumulation over 3 weeks, it was dem-
onstrated that peri-implant soft tissues
developed a stronger inflammatory response
to experimental plaque accumulation com-
pared with that of the gingiva at teeth. The
experimentally induced gingivitis and peri-

2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 15
Renvert & Quirynen
Risk indicators for peri-implantitis
implant mucositis were reversible as assessed
by biomarkers, whereas clinically, 3 weeks of
resumed plaque control did not yield pre-
experimental levels of gingival and peri-
implant mucosal health (Salvi et al. 2012). In
a recent systematic review, on risk indicators
for peri-implant mucositis, it was concluded
that plaque accumulation adjacent to dental
implants would result in the development of
peri-implant mucositis (Renvert & Polyzois
2014). If such an inflammation persists, it
may result in the resorbtion of the implant-
supporting bone. Long-term clinical studies
have demonstrated a significant correlation
between poor oral hygiene and peri-implanti-
tis (Lindquist et al. 1996; Ferreira et al.
2006).
Even if the infectious etiology of peri-im-
plantitis is well established, data on the
microbial composition of the infection at
dental implants indicate that this infection
may be more complex than what has been
reported in cases of periodontitis. The infec-
tion at dental implants has been described as
a poly-microbial anaerobic infection but may
differ in bacterial composition to what has
been reported in periodontitis lesions (Koyan-
agi et al. 2010, 2013; Charalampakis et al.
2012; Maruyama et al. 2014; Persson & Ren-
vert 2014).
The etiology of peri-implantitis is multifac-
torial, and some individuals seem to be more
prone to its development than others. An
individuals specific susceptibility may
increase the risk for the development of peri-
implantitis and ultimately loss of the dental
implant. Conditions that are related to the
development of the disease are considered to
be risk factors. As defined by Genco et al.
(1996), a risk factor is an environmental,
behavioural, or biological factor that if pres-
ent directly increases the probability of a dis-
ease occurring and, if absent or removed
reduces that probability. The documentation
of risk factors requires longitudinal data and
demonstration of causality.
Such risk factors can be either local or gen-
eral. Local risk factors are factors that may
influence the bacterial composition and the
bacterial load at implants. Examples of such
factors are roughness of the implant surface
(Teughels et al. 2006), inaccessibility for oral
hygiene (Serino & Str om 2009), remaining
untreated periodontal pockets (Quirynen
et al. 1996; Sumida et al. 2002; Aoki et al.
2012), deep peri-implant pockets (Mombelli
et al. 1995; Renvert et al. 2007), the implant
supra-structure connection (Mawhinney et al.
2015), the surface structure of the implant
(Renvert et al. 2011), and the absence of
16 | Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544
keratinized tissue adjacent to the implant
(Lin et al. 2013).
General risk factors are factors related to
the individual and factors that may influence
the patients susceptibility to infection. Risk
factors that are often highlighted in this
aspect are a history of periodontal disease
(Daubert et al. 2015; Renvert et al. 2014),
genetic predisposition (Laine et al. 2006),
smoking habits (Rinke et al. 2011), the indi-
viduals general health status (Renvert et al.
2014), diseases like diabetes mellitus (Dau-
bert et al. 2015), and the individuals motiva-
tion to attend supportive care visits and
willingness to perform adequate oral hygiene
measures (Rinke et al. 2011; Roccuzzo et al.
2012). To avoid the development of peri-im-
plantitis, it has been proposed that patients
supplied with dental implants should be
enrolled in a structured maintenance pro-
gram in a similar way as periodontal patients
(Rinke et al. 2011; Costa et al. 2012; Pjeturs-
son et al. 2012b).
At present, there are limited scientific data
on different risk factors for peri-implantitis.
The aim of this review is to examine the
existing evidence in identifying risk factors
in the etiology of peri-implantitis.
Literature search
For the different subject headings, a literature
search was performed in MEDLINE via Pub-
Med database of the US National Library of
Medicine, for articles published until October
2014 using Medical Subject Heading search
terms + free text terms and in different com-
binations. To be included in the study, stud-
ies had to (i) be written in the English
language, (ii) be published in an international
peer-reviewed journal, and (iii) have a clear
definition for peri-implantitis or the presence
of clinical data/assessed parameters, which
the reviewers could reliably translate to peri-
implantitis. An additional search was also
performed to find additional relevant publica-
tions.
Local risk factors influencing the
bacterial composition and/or the
bacterial load at implants
Oral hygiene
As soon as the dental implant is exposed in
the oral cavity, microbial colonization of the
exposed implant surface occurs (Quirynen
et al. 2006; F
urst et al. 2007). In a prospective
study by Lindquist et al. (1996), poor oral
hygiene was associated with peri-implant
2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
bone loss. In a subsample from the original
47 individuals included in the study (13 indi-
viduals with good oral hygiene and 14 indi-
viduals with poor oral hygiene), bone loss
around implants differed at 10 years. A mean
bone loss of 0.65 mm was found in the group
with good oral hygiene compared to 1.65 mm
in the group with bad oral hygiene. Improper
accessibility for oral hygiene at the implant
sites was related also to peri-implantitis (Seri-
no & Strom 2009). In this study, 48% of the
implants presenting peri-implantitis were
those with no accessibility/capability for
proper oral hygiene. In this part of the
review, papers identifying the level of plaque
accumulation related to the presence of peri-
implantitis were assessed.
Results
Ferreira et al. (2006) analyzing risk factors for
peri-implant disease reported very poor oral
hygiene to be a risk factor for peri-implant
disease (OR 14.3 (95% CI: 9.128.7) P = 0.002
(Table 1). In a cross-sectional study, Roos-
Jans
aker et al. (2006c) reported that the pres-
ence of plaque was explanatory for the out-
come event peri-implant mucositis but not
for peri-implantitis. In a 5-year follow-up
study, Costa et al. (2012) reported plaque to
be a significant factor for the development of
peri-implantitis.
Discussion
Plaque accumulation adjacent to dental
implants is clearly associated with the devel-
opment of peri-implant mucositis (Renvert &
Polyzois 2014). Peri-implant mucositis may,
however, not always result in the develop-
ment of peri-implantitis, but in cases where
peri-implantitis develops, an infection has
been demonstrated to be a prerequisite for
the disease (Ericsson et al. 1992; Leonhardt
et al. 1993; Pontoriero et al. 1994; Salvi et al.
2012). The present review identified two
papers that reported plaque accumulation to
be associated with peri-implantitis (Ferreira
et al. 2006; Costa et al. 2012). In a cross-sec-
tional paper by Roos-Jans aker et al. (2006c),
an association between plaque and peri-
implant mucositis, but not with peri-implan-
titis, was reported. As peri-implantitis takes
time to develop and the presence of plaque at
teeth and/or implants may vary over time, a
cross-sectional design may be a less suitable
study design to evaluate such a relationship.
Microbial biofilm composition
Aggregatibacter actinomycetemcomitans
(A. actinomycetemcomitans), Porphyromon-
as gingivalis (P. gingivalis), and Tannerella
 Renvert & Quirynen
Risk indicators for peri-implantitis

Table 1. Plaque as a risk indicator for peri-implantitis

Study Subjects Implant type Purpose of Study Evaluationperiod Results Comments

Ferreira et al. 212 patients Nobel BioCare To investigate the 6 months5 years The association between The OR for plaque score,
(2006) 578 Implants Intra-lock & 3i prevalence and risk plaque scores and peri- considered very poor for
variables of peri- implant disease was dose peri-implantitis (OR = 14.3,
implant disease. dependent 95% CI 9.128.7), was
much higher when
compared with the same
level of plaque scores in
peri-implant mucositis
(OR = 2.9, 95% CI2.0
4.1)
Roos-Jans aker 218 patients anemark
Br To analyse risk 914 years On an implant level: the There was no uniform
et al. (2006c) 999 Implants Nobelpharma factors associated presence of plaque was supportive periodontal
with peri-implant explanatory for the treatment or recordings
lesions outcome event peri-implant of plaque index over time,
mucositis but not for peri- which may have affected
implantitis the results of this study
The cross-sectional design
makes it difficult to
interpret data on the
influence of plaque on
the development of
peri-implantitis
Costa et al. 80 individuals Nobel Biocare, To determine the 5 years In both groups, plaque The incidence of peri-
(2012) 39 received (30.3%) influence of index was a significant implantitis was high in
preventive 3i Implant demographic, factor for peri-implantitis both groups, and the
maintenance Innovation behavioural, and employing a univariate average amounts of
41 did not Inc. (33.5%) biological risk analysis (P < 0.003 and maintenance visits were
receive Intra- Lock variables in the P < 0.001, respectively) low (5.6  0.3 visits in
maintenance (36.2%) incidence of peri- whereas in the logistic 5 years)
implantitis regression analysis, the Bleeding on peri-implant
factors associated to probing, periodontal
peri-implantitis were: probing depth, and the
in the maintenance presence of periodontitis
group were associated with a
: >50% of sites with BOPi higher risk of developing
(OR = 37.27) and peri-implantitis
>5% of sites with PD Approximately only 1
4 mm visit per year in the
(OR = 19.6) were maintenance group
associated with peri-
implantitis;
in the non-maintenance
group:
>5%of sites with PD 4 mm
(OR = 25.49).
The presence of
periodontitis (OR = 11.43)
was associated with peri-
implantitis.
In the total sample
>50% of the sites with
BOPi (OR = 17.69), >5% of
sites with PD 4 mm
(OR = 16.39), the lack of
maintenance (OR = 5.92),
and
the presence of
periodontitis (OR = 9.20)
were associated with peri-
implantitis

forsythia (T. forsythia) are key pathogens in
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ransky 1994) and probably also play a signifi-
cant role in the development and progression
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tis (Mombelli et al. 1987; Leonhardt et al.
1993; Shibli et al. 2008; Mombelli & Decail-
let 2011). The presence of periodontopathic
bacteria has been proposed as a risk indicator
for peri-implant mucositis (Renvert & Polyz-
ois 2014). The microenvironment (i.e. sulcus/
pockets) around implants may favor the colo-
nization of anaerobic Gram-negative bacteria.
An interaction within the biofilm may also
contribute to the aggregation of microorgan-
isms allowing for the destruction of the peri-
implant tissues. The microbiota associated
with peri-implant disease may be described
as a poly-microbial anaerobic infection
(Koyanagi et al. 2010, 2013; Mombelli &
Decaillet 2011; Al-Radha et al. 2012;

2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 17 | Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544

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 Table 2. Biofilm as a risk indicator peri-implantitis clinical studies
Number of patients/ Methodology/Parameters
Study implants Purpose of study assessed Results Comments
Leonhardt 37 subjects To evaluate qualitative Samples obtained by paper At implants with peri-implantitis, The two types of clinical conditions
et al. (1999) peri-implantitis differences in the subgingival point sampling technique. putative periodontal pathogens, showed distinct bacterial profiles
Cross- 51 Subjects microbiota at titanium Bacteria cultured and such as P. gingivalis, P. intermedia, In areas with peri-implantitis,
sectional Healthy implants implants, demonstrating peri- identified by morphology P. nigrescens, and staphylococci, enterics, and yeasts were as
implantitis as compared to and Gram-staining and A. actinomycetemcomitans, were frequently found indicating differences as
clinically healthy implants biochemical tests found in 60% of the cases compared to the microbiota around
Staphylococcus spp., enterics and periodontitis-affected teeth
Candida spp., were found in 55%
of the peri-implant lesions
Clinically healthy implants
demonstrated a microbiota
associated with periodontal health

2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Hultin et al. 17 patients To characterise microbiota Checkerboard DNADNA In patients, all 12 tested Higher amounts of microorganisms were
(2002) 45 peri-implantitis around healthy and diseased hybridisation was used for microorganisms were found recovered at peri-implantitis sites
Cross- 53 stable implants implants and teeth the analysis of P. gingivalis, around teeth and implants
sectional 133 teeth P. intermedia, The specific periodontal pathogens
19 controls P. nigrescens, B. forsythus, tested, that is P. gingivalis,
144 healthy implants A. actinomycetemcomitans, P. intermedia, B. forsythus,
106 teeth F. nucleatum, T. denticola, A. actinomycetemcomitans, and
P. micros, C. rectus, T. denticola, were present at all
E. corrodens, S. noxia, and categories of sites in patients and
S. intermedia controls
A. actinomycetemcomitans in
amounts of >106 of were never
recovered at stable implants and
teeth in peri-implantitis patients,
but were present in 23.5% of the
samples from peri-implantitis sites

19 |
Shibli et al. 44 subjects To compare the microbial Samples taken with plastic All species present in both groups Peri-implantitis sites comprised of more
(2008) 22 Peri-implantitis composition of supra- and curettes The peri-implantitis group periodontal pathogens as compared to
Cross- 22 Healthy subgingival biofilm in subjects Thirty-six species were presented with higher mean healthy sites
sectional with and without peri- identified by the counts of P. gingivalis,
implantitis checkerboard DNADNA T. denticola, and T. forsythia
hybridization method (P < 0.05)
Marked differences were observed
in the composition of supra- and
subgingival biofilm between
healthy and diseased implants

Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544

Renvert & Quirynen
Risk indicators for peri-implantitis
 Table 2. (continued)
20 |
Number of patients/ Methodology/Parameters
Study implants Purpose of study assessed
Botero et al. 11 subjects The study aimed to identify the Subgingival microbial
(2005) 14 implants with peri- subgingival microbiota around samples from peri- implant
Cross- implantitis implants with peri-implant lesions, neighbouring, and
sectional 8 subjects lesions, stable implant,s and at non-neighbouring teeth to
15 healthy implants adjacent natural teeth in the corresponding affected
partially edentulous patients implant
Stable implants were also
sampled
The samples were analysed
using microbial culture
techniques for the presence
of
A. actinomycetemcomitans,
P. gingivalis, P. intermedia/
nigrescens
T. forsythensis,
Campylobacter spp.,
Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544
Eubacterium spp.,
Fusobacterium spp.,
Peptostreptococcus micros,
E. corrodens,
Capnocytophaga spp.,
Dialister pneumosintes,
Gram- negative enteric
rods, b-hemolytic
streptococci, Staphylococci
spp., and yeasts
Renvert et al. 213 subjects To assess the microbiota at Samples from the four sites
(2007) 55 healthy implants diagnosed with peri- with the deepest probing
Cross- 127 mucositis implantitis, implant mucositis, depth at and from implant
sectional 31 peri-implantitis or being clinically healthy sites were taken
976 Implants Forty species were
identified by the
checkerboard DNADNA
hybridization method
2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Results Comments
A statistical difference between This study detected superinfecting
peri-implant lesions and stable organisms of the families
implants for enteric rods and Enterobacteriaceae, Pseudomonadaceae,
P. intermedia/nigrescens (P < 0.05) and periodontopathic bacteria in implants
was reported with peri-implant inflammatory lesions
P. gingivalis (43.7%) was detected among patients compared to controls
in peri-implant lesions, but not in Data indicate that microorganisms may
stable implants transmit from residual pockets at
In 12 peri-implant lesions, it was neighbouring teeth to implants
possible to identify the enteric
microorganism
The microbiota around diseased
implants comprised high levels of
periodontopathic and
superinfecting bacteria
The microbiota around natural
teeth in patients with peri-implant
Renvert & Quirynen
Risk indicators for peri-implantitis
lesions was predominantly
composed of enteric rods
Fusobacterium spp. and
P. gingivalis. A significant
correlation was found between
the subgingival colonization
around implants and neighbouring
teeth for Gram-negative enteric
rods (P = 0.023)
Neisseria mucosa, Fusobacterium Few differences were found related to
nucleatum sp. nucleatum, implant status. This suggests that other
F. nucleatum sp. polymorphum, pathogens than the studied may be
and Capnocytophaga sputigena involved in the disease process
dominated the implant Differences between in the microbiota
submucosal microbiota and the between dentate and edentulous subjects
sub-gingival microbiota at tooth were marginal. This indicate that implant
sites placement in an edentulous oral cavity
The deepest probing depth at creates an microenvironment (i.e. sulcus/
implants was correlated with levels pockets) around the implant favoring
of Eikenella corrodens (P < 0.05), bacterial colonization
F. nucleatum sp. vincentii
(P < 0.05), P. gingivalis (P < 0.05),
and Micromonas micros (P < 0.01)
No differences in the microbiota
between implant and tooth
samples were found in subjects as
defined as having implant
mucositis, or peri-implantitis, or
having no clinical evidence of
mucositis or peri-implantitis
Independent of implant status
individuals with teeth had
significantly higher levels of
P. gingivalis and Leptotricia
buccalis (P < 0.05)
 Table 2. (continued)
Number of patients/
Study implants Purpose of study
Koyanagi et al. 3 Subjects To examine the microbial
(2010) 2 healthy Implants
3 implants with peri-
implantitis
3 teeth with
periodontitis
Casado et al. 30 subject To evaluate the presence of
2011; 1.Healthy implants
(n = 10), 2. Peri-implant
mucositis (n = 10)
3. Peri-implantitis
(n = 10)
2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Ebadian et al. 69 Subjects To compare the prevalence and
(2012) 1. Chronic periodontitis
(n = 22), 2. Non-
periodontitis (n = 21)
3. Peri-implantitis
(n = 13), 4. Healthy
implants (n = 13)
Cortelli et al. 306 subjects To evaluate the presence of
(2013) Peri-implantits health
(n = 53)
Periodontal health
21 |
(n = 53);
Mucositis (n = 50),
Gingivitis (n = 50), Peri-
implantitis (n = 50)
Periodontitis (n = 50)
Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544
Methodology/Parameters
assessed
The prevalence of bacteria
differences between clinically was analysed using a 16S
healthy implants and rRNA gene clone library
periodontitis in the same and real-time polymerase
subjects chain reaction
Samples of crevicular fluid
periodontal pathogens in were collected, and nested
healthy and in peri-implantitis PCR was used to detect the
sites following periodontal
pathogens
A. actinomycetemcomitans
P. gingivalis, P. intermedia,
T. forsythensis, T. denticola
Checkerboard DNA-DNA
amounts of 10 periodontitis- hybridization technique for
associated bacterial species in analysis of:
periodontitis and peri- P. gingivalis, P. nigrescens,
implantitis cases P. intermedia, T. denticola,
P. tannerae,
A. actinomycetemcomitans,
T. forsythia,
P. endodontalis,
F. nucleatum, and C. rectus
Prior to microbial analysis,
P. gingivalis, T. forsythia, polymerase chain reaction
C. rectus, P. intermedia (PCR) was carried out using
T. denticola, and unspecific Universal
A. actinomycetemcomitans in primers (16S rRNA) to
different clinical situations detect bacterial DNA in the
samples
Results
The microbial composition of peri-
implantitis was more diverse than
that of periodontitis
Low levels of periodontopathic
bacteria, such as P. gingivalis and
A. actinomycetemcomitans, were
seen in peri-implant lesions
Most of the bacterial species
found in the healthy implants
were also detected in the peri-
implantitis and periodontitis sites
There were no differences
(P > 0.05) in the detection
frequencies of the Aa, Pg, Pi, and
Td within healthy and diseased
groups
All species demonstrated a higher
incidence in the periodontitis sites
than in the healthy sites
37.5% of species showed a higher
prevalence in the peri-implantitis
site than healthy implant sites
No significant differences between
peri-implantitis and healthy
implant were observed for any of
the analysed species
Bacterial frequency was higher in
peri-implantitis than health
(P < 0.05)
P. gingivalis and red complex
species were more common in
peri-implantitis than mucositis
(P < 0.05)
C. rectus and T. forsythia were
more frequent in healthy teeth/
gingivitis than healthy implants/
mucositis, respectively (P < 0.05)
P. gingivalis and
A. actinomycetemcomitans were
similar in periodontitis and peri-
implantitis (P > 0.05), while all
other species occurrences were
higher in periodontitis than peri-
implantitis (P < 0.05)
Comments
Although very few individuals were
examined, the technique employed allows
for the detection of almost every species
in a given sample and is able to indicate
the presence of previously unknown
bacteria
The biofilm in peri-implantitis showed a
more complex microbial composition
when compared with periodontitis
Periodontal pathogens were present in
healthy, peri-implant mucositis, and peri-
implantitis sites, indicating that these
microorganisms are not strictly associated
with peri-implantitis
This study compared the prevalence and
amounts of 10 periodontitis associated
bacterial species
Other species then the ones analysed may
be related to peri-implant disease
A higher bacterial frequency was found at
teeth
Comparing bacterial frequencies between
peri-implantitis and mucositis similarities
were more evident than differences
As periodontal pathogens were analysed,
it is possible that other species not
analysed in the study may be involved in
peri-implant disease pathogenesis
Renvert & Quirynen
Risk indicators for peri-implantitis
 Table 2. (continued)

22 |
Number of patients/ Methodology/Parameters
Study implants Purpose of study assessed Results Comments
Koyanagi et al. 6 subjects To examine the microbial The prevalence of bacteria The microbial composition of peri- Few individuals were examined, but the
(2013) 6 implants with peri- differences between peri- was analysed using a 16S implantitis was more diverse than technique employed allows for the
Cross- implantitis implantitis and periodontitis in rRNA gene clone library that of periodontitis detection of almost every species in a
sectional 6 teeth with the same subjects and real-time polymerase Fusobacterium spp. and given sample and is able to indicate the
periodontitis chain reaction Streptococcus spp. were presence of previously unknown bacteria
predominant in both peri- Common periodontopathic bacteria
implantitis and periodontitis showed low prevalence, The biofilm in
Parvimonas micra were only peri-implantitis were more complex
detected in peri-implantitis compared to periodontitis
Dabdoub et al. 81 subjects The authors investigated the Bacterial DNA was isolated, 523 species were identified It appears that geographic proximity is not
(2013) idea that neighbouring teeth and the 16S rRNA gene was Sixty percent of individuals shared sufficient to fully determine the
Cross- influence the microflora amplified and sequenced <50% of all species between their inhabitants of a microenvironment
sectional surrounding osseointegrated by pyrotag sequencing periodontal and peri-implant Staphylococcus and Treponema were
dental implants Thirteen of the diseased biofilms and 85% of individuals significantly associated with diseased
The species shared between teeth (DT) represented shared <8% of abundant species implants, but not teeth
the tooth-implant pairs from gingivitis and 12 between tooth and implant
each participant were analysed represented periodontitis, Peri-implant and periodontal

Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544

Renvert & Quirynen
Risk indicators for peri-implantitis

while 20 diseased implants microbes represent

(DI) represented peri-
implant mucositis and 20
represented peri-implantitis
Tamura et al. 30 Subjects To compare predominant The bacterial strains were
(2013) 15 Healthy and 15 Peri- species at peri-implantitis and identified by 16S rDNA
Cross- implantitis healthy sites at implants gene-based polymerase
sectional chain reaction and
comparison of the gene
sequences
Albertini et al. 33 Subjects To compare the microbiota at Clinical study
(2014) 48 implants implants with a diagnosis of A. actinomycetemcomitans,
Cross- peri-implantits and teeth with P. gingivalis, P. intermedia,
sectional periodontitis T. forsythia, and
T. denticola were
determined by PCR
Staphylococcus aureus,
enteric Gram-negative
bacteria, Pseudomonas
spp., and Candida albicans
were evaluated using
culture techniques
microbiologically distinct
ecosystems
Distinct bacterial lineages were
associated with health and disease
in each ecosystem
The periodontal microbiome
demonstrated significantly higher
diversity than the implant
The predominant bacterial species Peri-implantitis sites had approximately 10-
in peri-implantitis sites were fold higher mean colony-forming units
Eubacterium nodatum, E. brachy, (per milliliter) than healthy implant sites
E. saphenum, Filifactor alocis, Conventional periodontal pathogens may
Slackia exigua, Parascardovia not be the only microorganisms active in
denticolens, Prevotella intermedia, peri-implantitis
Fusobacterium nucleatum, High levels of asaccharolytic anaerobic
Porphyromonas gingivalis, gram-positive rods and gram-negative
Centipeda periodontii, and rods were found
Parvimonas micra
Healthy sites were:
Streptococcus, Pseudoramibacter
alactolyticus, Veillonella species,
Actinomyces israelii, Actinomyces
species, Propionibacterium acnes,
and Parvimonas micra
No significant differences were Staphylococcus aureus, P. aeruginos,a and
found between implants and teeth C. albicans were only studied in implants,
for the prevalence of the so no comparison with teeth could be
periodontopathic bacteria, done. However, 15% of the patients
P. gingivalis, T. forsythia, harboured these species
P. intermedia, or T. denticola

2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
 Table 2. (continued)
Number of patients/ Methodology/Parameters
Study implants Purpose of study assessed Results Comments
Persson & 213 Subjects To analyse whether the DNA-DNA checkerboard Nineteen bacterial species were Clear differences were observed between
Renvert 166 Peri-implantitis microbiota differ by implant hybridization method. found at higher counts from healthy implants and implants diagnosed
(2014) 47 Healthy status. Seventy-eight different implants with peri-implantitis with peri-implantitis
Cross - species analysed. (Aggregatibacter Microorganisms not associated with
sectional actinomycetemcomitans, periodontal disease were a common
Campylobacter gracilis, finding at implants with peri-implantitis
Campylobacter rectus, A cluster including T. forsythia and
Campylobacter showae, Staphylococcus aureus are associated with
Helicobacter pylori, Haemophilus peri-implantitis
influenzae, Porphyromonas
gingivalis, Staphylococcus aureus,
Staphylococcus anaerobius,
Streptococcus intermedius,
Streptococcus mitis, Tannerella
forsythia, Treponema denticola,
and Treponema socranskii
(P < 0.001))
A cluster consisting of T. forsythia,

2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
P. gingivalis, T. socranskii,
Staph.aureus, Staph.anaerobius,
Strep.intermedius, and Strep. mitis
comprised 30% of the total
microbiota in peri-implantitis
Maruyama 20 Subjects To compare the microbiological Clinical study Compared with periodontitis, peri- Porphyromonas gingivalis, Treponema
et al. (2014) 20 implants features between peri- Sequences for the 16S rRNA implantitis-associated bacterial denticola, and Tannerella forsythia were
Cross- implantits and periodontitis gene were used for the communities had significantly abundant and prevalent in most samples
sectional analyses. From these higher levels of the genera in both diseases
sequences, 19 phyla, 188 Olsenella, Sphingomonas,
genera, and 235 species Peptostreptococcus, and
were identified) unclassified Neisseriaceae
Lower levels of the genus
Desulfomicrobium
Zhuang et al. Twenty-two Individuals To compare the prevalence and Subgingival/submucosal Staphylococcus aureus and Within the same subjects, putative
(2014) Four sites were selected levels of 6 microorganisms plaque was sampled using F. nucleatum was the most periodontal pathogens were common to

23 |
for microbiological within the subgingival/ paper points commonly detected species both periodontal and peri-implant sites
sampling within each submucosal microbiota at teeth Quantitative real-time No statistically significant irrespective of health status
subject vs. implants with various polymerase chain differences in the bacterial loads Both periodontal and peri-implant sites,
(1) healthy peri- clinical conditions reaction (q-PCR) was used were found among the four irrespective of their health status
implant tissues; to quantify, P. gingivalis clinical sites; with the exception of harboured S. aureus
(2) peri-implantitis (3) (P.g.), T. denticola (T.d.), F. nucleatum. This was more
healthy gingiva; (4) A. actinomycetemcomitans abundant in periodontitis sites
periodontitis (A.a) (P = 0.023)
F. nucleatum (F.n.) The prevalence and levels of
P. intermedia (P.i.), and P. gingivalis and F. nucleatum
Staphylococcus aureus (S.a.) were significantly associated with
periodontitis but not with peri-
implantitis (P < 0.001)

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Renvert & Quirynen
Risk indicators for peri-implantitis
Renvert & Quirynen
Risk indicators for peri-implantitis
panel of microorganisms, species not associ-
ated with periodontitis were commonly
found (Renvert et al. 2008; Persson & Ren-
vert 2014). The presence of microorganisms
not primarily associated with periodontitis
such as Staphylococcus aureus and Entero-
bacteriaceae and Candida albicans has also
been reported as frequent findings at
implants with peri-implantitis in studies
using culturing techniques for analysis (Leon-
hardt et al. 1999; Botero et al. 2005; Albertini
et al. 2014). As titanium implants may pro-
vide an ecological niche different from that
of teeth, the biofilm formed may include
other and possibly currently unknown bacte-
ria. Recent papers employing the 16S rRNA
gene clone library to make a broader analysis
of the microbiota indicate that periodontitis
and peri-implantitis may to some degree
share microorganisms, but also that the
microbial composition between the diseases
differ (Koyanagi et al. 2010, 2013; Tamura
et al. 2013; Maruyama et al. 2014). Accord-
ingly, based on papers with a broader
approach to analyze samples from sites with
a clinical diagnosis of peri-implantitis, it
seems like the microbiota associated with
peri-implantitis demonstrate distinct differ-
ences to the one seen at periodontitis. Micro-
organisms like Staphylococcus, Enteric rods,
and Candida are often found in cases of peri-
implantitis.
The significant correlation observed
between parts of the subgingival microbiota
in peri-implant lesions and natural teeth,
however, suggests that natural teeth may act
as a reservoir for the colonization of patho-
gens in partially edentulous patients (Botero
et al. 2005; Renvert et al. 2007; Koyanagi
et al. 2010, 2013; Albertini et al. 2014; Mar-
uyama et al. 2014). The geographic proximity
may not be sufficient to determine the inhab-
itants of the microenvironment (Dabdoub
et al. 2013).
The fact that probing depth at implants has
been highlighted as an ecological factor for
microbial growth that may favor certain
microorganisms (Renvert et al. 2007) indi-
cates that initially deep pockets at implants
may serve as a risk indicator for peri-implant
disease. The number of sites with residual
probing depths (5 mm) following periodontal
therapy in periodontitis-susceptible patients
supplied with dental implants has also been
reported to be a risk indicator for peri-im-
plantitis (Pjetursson et al. 2012b). As the
probing depth has been reported to be of
importance for the bacterial profile, it would
be of importance to analyze the bacterial pro-
file of chronic periodontitis and peri-implan-
24 | Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544
titis cases selected so that they show similar
probing depths and clinical signs of disease
(bleeding on probing and/or pus).
Microbiota at implants in fully and partially
edentulous patients
In partially edentulous subjects (PES), freshly
inserted implants can be colonized by micro-
organisms originating from the neighboring
teeth, the saliva, and/or the soft tissues,
whereas in fully edentulous subjects (FES),
only the soft tissues and the saliva can serve
as origin (Lekholm et al. 1986; Leonhardt
et al. 1993; Mombelli et al. 1995; Gouvoussis
et al. 1997; van Winkelhoff et al. 2000; Quiry-
nen et al. 2001, 2006; Mager et al. 2003; Van
Assche et al. 2009; Quirynen & Van Assche
2011). One can therefore question whether
this might have an impact on the maturing
biofilm along implants and as such on their
susceptibility to primary peri-implantitis.
To be included in this part of the review,
the studies had to include separate data on
FES and PES (for details see de Waal et al.
2014).
Results
Eleven papers (10 trials) one prospective ran-
domized control trial and nine cross-sectional
studies were included in the present review
(Table 3). Three papers compared healthy
subjects to subjects with peri-implantitis/
periodontitis. Analysis was mostly performed
by phase contrast microscopy or culture tech-
nique in the older studies, whereas polymer-
ase chain reaction (PCR) technique was
commonly applied in the more recent stud-
ies. In five studies, the teeth of the PES group
were also sampled.
Available studies on morphotypes are con-
tradictory (Apse et al. 1989; Quirynen & List-
garten 1990; Papaioannou et al. 1995; Hultin
et al. 1998; Kocar et al. 2010). Three studies
indicated higher proportions of cocci in the
FES group. One study reported no difference,
and finally, one paper (Apse et al. 1989)
observed the opposite. Two papers found
more motile organisms in PES than in FES,
but again the paper by Apse et al. (1989) sug-
gested the opposite.
The analysis of specific bacterial species
was performed by different methods. Apse
et al. (1989) using culture techniques found
significantly more black-pigmented anaerobes
around PES, compared to FES, and within
PES, more often at implant sites than around
teeth. A. actinomycetemcomitans was only
detected around PES. Hultin et al. (1998,
2002), however, could not find significant dif-
ferences between PES, FES, or teeth. Leon-
2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
hardt et al. (1999) compared healthy and peri-
implantitis sites, both in PES and FES. A. ac-
tinomycetemcomitans, P. gingivalis, and
P. intermedia could not be detected in FES
without peri-implantitis, and only rarely in
PES without peri-implantitis. However, in
peri-implantitis cases, their detection fre-
quency was clearly higher, especially in PES.
Two studies (Hultin et al. 2002; Quirynen &
Van Assche 2012) used the checkerboard
DNADNA hybridization technique, how-
ever again with conflicting observations. Kar-
bach et al. (2009) and Kocar et al. (2010)
applying the PCR technique found signifi-
cantly lower percentages of implants with
periodontal pathogens in FES compared to
PES. Quirynen & Van Assche (2012) used
qPCR to follow the microbial changes over
time in PES and FES. The dynamics of bio-
film formation presented remarkable differ-
ences. At day 3, both PES and FES showed
comparable biofilms. After 2 weeks, FES had
a quite stable biofilm that did not change up
to 1 year. The biofilm of PES, however, had a
further maturation up to 1 year. At 1 year,
the authors reported a lower concentration of
specific periodontal pathogens in FES com-
pared to PES.
Discussion
The papers selected for this part of the
review demonstrated major diversities in
design, methods to analyze the microbiota,
and patient selection. These differences may
possibly explain the conflicting outcomes of
the studies. The majority of papers, however,
indicated differences in microbiota compar-
ing FES and PES, with FES harboring a less
pathogenic plaque (Zambon 1996; Mager
et al. 2003; Shibli et al. 2008). This is in
agreement with data recently published by de
Waal et al. (2013). The authors concluded
that FES presented with higher plaque scores
around their implants than PES. The modi-
fied bleeding index scores were significantly
higher in FES, but no differences in bleeding
on probing, implant loss, and probing pocket
depth were observed between FES and PES.
No meta-analysis could be performed on the
prevalence of peri-implant mucositis and
peri-implantitis.
Using checkerboard analysis of fully eden-
tulous patients wearing an overdenture on
implants for 10 years, periodontal pathogens
were only detected at low proportions (Quiry-
nen et al. 2005). Whether the higher concen-
tration of putative periodontal pathogens in
partially edentulous patients can lead to
higher incidences on peri-implantitis remains
at present an unanswered question.
 Table 3. Variation in microflora between fully (FES) and partially edentulous subjects (PES) for plaque samples from teeth (T) and implants (I) considering either morphotypes or specific spe-
cies, the latter identified via cluture techniques*, PCR , latex agglutination test , or checkerboard . In some studies, a distinction was made between implants with (I/PI) and without peri-
implantitis (I/st) and/or patients with (+ PI) or without (no PI) implants with peri-implantitis
Clinical Status Morphotypes Detection frequency-specific species %

Dental % plaque %BOP or BI PD (mm) Authors

Authors status Sample # or PI (SD) (SD/range) (SD/range) Cocci Others Motile rods Spiros Aa Pg Pi Tf Td Fn BPA conclusions
Apse et al. FES 13 I 1.23 (1.01) 55% 3.04 (0.83) 85.1 5.8 5.9 4.5 0* NR 9.1 FES: S > motile forms
(1989) PES 28 I 0.93 (0.88) 36% 3.46 (1.08) 87.1 7.9 2.7 4.3 3.6 50 PES: S > BPAs
19T 0.95 (0.6) 42% 2.55 (0.46) 87.1 7.4 4.3 8.7 15.8 31.6 PES: BPA S > at I vs. T
Quirynen & FES 11 I 1.27 (0.15) 0.64 (0.2) 2.59 (0.2) 71.3 28.4 0.4 0 NR FES: > %cocci and S < % mot
Listgarten PES 26 I 0.58 (0.2) 0.08 (0.04) 3.04 (0.1) 69 28 1.8 1.6 PES: no S # between T and I
(1990) 26 T 0.61 (0.2) 0.26 (0.08) 2.62 (0.1) 56 35 4.7 3.8
George et al. FES 114 I 11% 34% 3.49 (17) NR 12.3 19.3 NR PES: S > Pg & Pi
(1994) PES 82 I 27% 41% 17.0 39.0
Papaioannou FES 169 I 1.1 55% 3.3 60 38.1 1.4 0.5 NR FES: S > %cocci
et al. (1995) PES 143 I 0.8 55% 3.6 55 43.7 2.7 1.1 PES: > pathogens
Hultin et al. FES 15 I 0.7 (0.7) 1.5 (0.4) 2.7 (0.7) 55 NR 0.01* 0.04 NR 3.03 no S # PES vs. FES

2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
(1998) PES 16 I 1.0 (0.6) 1.6 (0.4) 2.5 (0.7) 3040 0 0 2.5 nor T vs. I
16 T 1.0 (0.6) 1.4 (0.5) 2.5 (0.6) 3040 0 0 0.1
Leonhardt FES noPI 16 I NR NR 0* 0 0 NR FES no PI: no pathogens.
et al. (1999) PES noPI 35 I 3 3 26 PES no PI: one or >
FES + PI 8 I 13 25 38 pathogens in 40% (S).
PES + PI 29 I 31 3 66 FES + PI: 62%.
PES + PI: 90%
Hultin et al. FES noPI 6 I 38.2% 0.9 (0.5) 2.2 (0.4) NR 100 83 50 17 67 67 NR Microflora PES = FES
(2002) PES noPI 13 I 69 53 62 15 46 100
13 T 63.7% 1.3 (0.6) 1.8 (0.4) 69 54 69 54 77 92
FES + PI 0 / / / / / / / / /
PES + PI 17 I/PI 33.7% 1.6 (0.4) 4.3 (1.0) 94 65 77 59 41 100
14 I/st 31.3% 1.1 (0.6) 2.6 (0.9) 93 79 50 36 43 100
14 T 62.7% 1.2 (0.6) 2.1 (0.5) 77 53 65 35 47 77
Karbach et al. FES 47 I 67% 55% 3 (111) NR 15 NR FES: S < pathogens
(2009) PES 53 I 34

25 |
Kocar et al. FES 19 I NR 0 4 mm 95% NR 0 5.3 0 0 0 NR FES: no Aa. Pg. Tf. Td
(2010) PES+Sp 19 I 0 4 mm 97% 21.1 36.8 5.3 57.9 47.4 PES no PI: # pathogens
19 T 14% 21.1 21.1 0 31.6 21.1 in PES: no correlation T vs I
PES+De 15 I 0 4 mm 13.3 73.3 0 33.3 33.3
15 T 41.8% 40 93.3 0 86.7 66.7
Quirynen & FES 1 y 20 I 20% 15% 2.7 (15) NR 80 50 100 100 NR After 1 year: PES group
Van Assche 45 90 60 35
(2012) PES 1 y 16 I 20% 40% 3.8 (27) 18.8 68.8 62.5 87.5
18.8 68.8 62.5 87.5

NR, not recorded; I, implant; I/PI, implant with peri implantitis; I/st, stable implant; Sp, shallow periodontal pockets; De, deep periodontal pockets; T, tooth; cocci, coccoid cells; others, non-motile rods,
fusiforms and/or filaments; motile rods, motile rods other than spirochetes; spiros, spirochetes; BPA, black-pigmented anaerobes; S, statistically significant.

Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544

Renvert & Quirynen
Risk indicators for peri-implantitis
Renvert & Quirynen
Risk indicators for peri-implantitis

Table 4. Excess cement as a risk indicator for peri-implantitis

Number of patients/
Study implants Study Evaluation period Results Comments
Linkevicius Test: 77 patients A retrospective study aiming to More than 6 months Peri-implant disease was evident in Patients with a history of
et al. 129 implants determine a relationship from the delivery of 62 of 73 implants with cement periodontal disease may
(2013b) (cemented between patients with a the restoration to remnants (85%) be more prone to
restorations) history of periodontitis and the the diagnosis of Group 1: develop peri-implant
Group 1: development of cement- complication All 39 implants developed peri- disease when tissues are
Patients with a related peri-implant disease implantitis exposed to residual
history of Group 2: (31 implants) cement
periodontitis 20 implants developed peri-
Group 2: implant mucositis, 3 implants early
Patients without peri-implantitis, and 11 implants
periodontal disease did not develop biological
complication
In the group of implants without
cement remnants, peri-implant
disease was diagnosed in 17 of 56
cases (30%)
Wilson 39 consecutive To explore the relationship Implants were Excess cement was not found at the Excess dental cement
(2009) patients with 42 between excess dental cement evaluated using a control implants but in 34 of the was associated with
implants exhibiting and peri-implant disease using dental endoscope diseased sites signs of peri-implant
clinical and/or the dental endoscope initially, and all but disease in 81% of cases.
radiographic signs one implant was Clinical and endoscopic
of peri-implant evaluated at a 30- signs of peri-implant
disease were studied day follow-up disease were absent in
20 control implants 74% of the test
(no clinical signs of implants after the
peri-implant disease) removal of excess
cement
Korsch 93 patients Retrospective analysis aiming at Group 1 Group 1. Removal of excess
et al. 171 implants analysing the clinical findings 0.7 years No excess cement cement significantly
(2015) Group 1 associated with excess cement Group 2 BOP:17.6% reduced the signs of
Treatment revisions Supra structures originally 4 years Pus: 0% inflammation
within 2 years of cemented with a methacrylate Excess cement Peri-implantitis was not
restoration cement were revised BOP: 80% defined
placement Pus 21.3%
71 patients (126 Group 2.
implants) Group 2 No excess cement
revisions conducted BOP: 94.1%
at a later time Pus: 23.3
22 patients (45 Excess cement
implants) BOP: 100%
Pus:29.3

Excess cement
Cemented supra-structures are a frequently
used alternative to screw retained prostheses
on dental implants. The use of cement-
retained implant restorations was found to
frequently result in leaving excess cement in
peri-implant tissues in spite of careful clini-
cal control following cementation of the
crown (Linkevicius et al. 2013b). In another
paper by Linkevicius et al. (2013a), it was
demonstrated that the deeper the position of
the crown margin, the greater the amount of
undetected cement discovered. It was also
highlighted that radiographic evaluation was
unpredictable in detecting excess cement. In
4 of 53 (7.5%) cases, implants with cement
remnants were visible mesially and in 6 of
53 (11.3%) cases distally. Accordingly, dental
radiographs were not considered a reliable
method for excess cement evaluation (Link-
evicius et al. 2013a). Excess cement may act
as a foreign body and thus provoke an
inflammatory response resulting in the
development of peri-implantitis. Such
cement remnants may be the basis of colo-
nization by oral microorganisms resulting in
the development of peri-implant mucositis
or peri-implantitis. In a recent paper by Kor-
sch et al. (2014), excess cement was sampled
from ten patients and investigated for bio-
film formation. The cement samples were
collected and analyzed for bacterial in situ
colonization by 16S rDNA-based methods.
The results of the in situ hybridization
revealed a strong tendency toward the bacte-
rial invasion of methacrylate-based cement
by opportunistic species and pathogens.
Studies evaluating the influence on the
development of peri-implantitis were ana-
lyzed in this part of the review.
Results
Three papers were retrieved, focusing on the
impact of excess cement on the development
of peri-implant disease (Table 4). Wilson
(2009) explored the relationship between
excess dental cement and peri-implant dis-
ease using the dental endoscope. He reported
that excess dental cement was associated
with signs of peri-implant disease in 81% of
cases. After the removal of excess cement,
clinical and endoscopic signs of peri-implant
disease were absent in 74% of the implants.
Linkevicius et al. (2013b) found that the peri-
implant disease was evident in 85% of
implants with cement remnants and that all
39 implants with cement remnants in a
group of patients with a history of periodonti-
tis developed peri-implantitis. A retrospective
analysis of the clinical findings associated
with excess methacrylate cement was a fre-
quent finding. Clinical observations of previ-
ously undetected excess cement were
associated with the increased prevalence of
inflammation evidenced by BOP and the
presence of pus (Korsch et al. 2015).

26 | Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
 Renvert & Quirynen
Risk indicators for peri-implantitis

Discussion

1.8% (165)ns

3.5% (455)ns
3.0% (497)ns

2.2% (283)ns

2.4% (127)ns

NR, not recorded; CCT, controlled clinical trial; R, retrospective analysis; perio, periodontitis patients; non-perio, patients without a history of periodontitis; #, no periodontitis classification; aggr, gener-
Although few papers exist on the association

3.7% (1803)
4.5% (647)

3.1% (747)
4.2% (47)?
Table 5. Incidence (in percentage) of implants failure (early and late together) in patients without or with a history of periodontitis (the latter subdivided in chronic and aggressive forms

Non-perio

8.3% (72)

0% (35)ns
between excess cement and peri-implantitis,

0% (60)?

0% (26)?
% implant failure rate (total

0% (2)?
3.8%*
number inserted implants)
the data clearly indicate that excess cement
may trigger the inflammatory response
resulting in clinical signs of peri-implant mu-
cositis/peri-implantitis.

10.4% (375)

5.2% (1171)
3.1% (2408)
4.5% (2938)

5.2% (1065)
14.3% (99)

20.8% (77)
8.2% (122)
25.0% (68)

4.4% (697)
3.3% (447)

0.7% (138)
5.0% (149)
8.1% (62)
0% (167) General risk indicators influencing

25.0%*
0% (7)
Perio

the patients susceptibility to

infection

History of periodontitis
Type perio

Depending on the criteria used to define peri-

Moderate

Moderate
odontitis, the prevalence of periodontitis has

Severe

Severe
been reported in the range of 1276% in the
#
#
#
#
#
#
#
#
#
#

#
#
United States (Albandar 2002; Eke et al.
2012). Globally, approximately 10% of the
population exhibits severe periodontal dis-
Follow-up mean (range)

ease. Individuals susceptible to periodontitis

have been reported to react differently to the
71 month (12193)
30.5 month (167)

microbial challenge than patients who are

8.4 year (116)
1134 month

not susceptible (Javed et al. 2011). Accord-

130 month
54 month
13.4 year

ingly individuals presenting with a history of

30 year
5 year
7 year
5 year
4 year

5 year

4 year

2 year

periodontitis may also be at an increased risk

for the development of peri-implantitis.
Several reviews on implant outcome vari-
*Data on a patient level, data in bold means statistically significant difference between # types of periodontitis.

ables concluded that patients with a history

sub mean (perio year/n)

of periodontitis exhibited, at long-term, sig-

alized aggressive periodontitis; ?, no statistical analysis on this parameter; ns, not significantly different.

nificantly greater probing depth, more mar-

(54, 50, 40)

ginal bone loss, and a higher incidence of

range (mean) or

NR (54, 46)

1850 (37, 42)

peri-implantitis compared with periodontally

(32.9)

(57.9)

(43.8)

NR (55.4)
43.7)

(NR)
(53)

(48)

(52)

healthy participants (Roos-Jans aker et al.

2006c; Schou et al. 2006; Karoussis et al.
1672

1690

2263

1494

1880

1785

(51)
(52.4,

NR

NR

NR

NR
Age

2007; Quirynen et al. 2007; Ong et al. 2008;

Renvert & Persson 2009; Roccuzzo et al.
2012).
Implant survival rates in periodontitis and
(1281/196)
(147/293)

(311/164)

717 (434/283)
perio (yes/no)

323 (230/93)

non-periodontitis patients have been ana-

(31/20)
(50/37)

(77/72)

(28/78)

46 (30/16)
60 (30/30)
(7/19)

(14/2)
n patients

lyzed in a number of papers (See Table 5 for

(NR)

(NR)

review). The studies presented in Table 5 all

51
87
440
143
26
149
891
16
106
475
1477

used similar criteria for implant survival.

A majority of these studies demonstrated
higher implant failure rates (often double)
in the periodontitis group when compared to
Study design

the non-periodontitis group. In a recent study

employing multivariate analysis, smoking
(P = 0.046) and history of periodontitis
CCT
CCT
CCT
CCT

CCT

CCT

CCT
R

R
R
R

R
R

(P = 0.046) were reported to affect the late

peri-implant bone loss (Vervaeke et al. 2014).
The presence of periodontal pathogens
Rosenquist & Grenthe (1996)

Wagenberg & Froum (2006)

Garcia-Bellosta et al. (2010)

around failing implants (Mombelli et al.

Ormianer & Patel (2012)

1987; Augthun & Conrads 1997; Salcetti

Buchmann et al. (1999)

Fardal & Linden (2008)

Koldsland et al. (2009)

Gianserra et al. (2010)

Brocard et al. (2000)

Watson et al. (1999)

et al. 1997; Leonhardt et al. 1999; Quirynen

Polizzi et al. (2000)

Anner et al. (2010)

Evian et al. (2004)

Levin et al. (2011)

Jiang et al. (2013)

& Teughels 2003; Shibli et al. 2008; Heitz-

Mayfield & Lang 2010; Meijndert et al. 2010)
could suggest a direct link between periodon-
Authors

titis and peri-implantitis, via a translocation

of these species from their intra-oral niches
to the freshly inserted implants as suggested

2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 27 | Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544
Renvert & Quirynen
Risk indicators for peri-implantitis

in several studies (Leonhardt et al. 1993; Qui- Results Discussion

rynen et al. 2006; F urst et al. 2007). In par-
tially edentulous patients, teeth could act as
reservoir, but also in fully edentulous
patients, periodontal pathogens remain
within the oral cavity, surviving either on
the tongue or in the saliva (Van Assche et al.
2009; Quirynen & Van Assche 2011; de Waal
et al. 2014).
An indirect link could also be considered,
where especially patients with aggressive
periodontitis, with their unfavorable immune
response toward periodontal pathogens inevi-
table, are more prone to infections around
implants. Clinical human studies, random-
ized or not, reporting on the incidence of
peri-implantitis with a distinction between
patients either with or without a history of
periodontitis (if doable, a categorization into
patients with chronic or aggressive periodon-
titis was carried out) was considered eligible
for this part of the review. Case reports, tech-
nical reports, animal studies, in vitro studies,
and review papers were excluded.
Seven papers (Table 6) reported on the inci-
dence of peri-implantitis in periodontitis and
non-periodontitis patients. These papers
reported higher percentages of peri-implanti-
tis in the patients with a history of periodon-
titis. Five studies (Karoussis et al. 2003;
Roos-Jans aker et al. 2006c; Simonis et al.
2010; Roccuzzo et al. 2012, 2014) even
reported a statistically significant difference
between periodontitis and non-periodontitis
patients. Many papers also reported on mar-
ginal bone loss around implants, and again,
higher values were found in the periodontitis
group (mostly 1.32.0 times more).
Five papers (Mengel & Flores-de-Jacoby
2005; Gatti et al. 2008; De Boever et al. 2009;
Roccuzzo et al. 2012, 2014), evaluating the
effect of periodontitis on the development of
peri-implantitis, made a distinction between
moderate vs. severe, or chronic vs. aggressive
periodontitis patients. In general, the severe/
aggressive forms of periodontitis were respon-
sible for the higher rates of peri-implantitis.
These data indicate that patients with a his-
tory of periodontitis are more prone to peri-
implantitis, marginal bone loss around
implants, and ultimately implant failure,
even though part of this association might be
explained by underlying mutual confounding
factors such as smoking. This has previously
been reported in a series of systematic
reviews (Schou et al. 2006; Karoussis et al.
2007; Quirynen et al. 2007; Ong et al. 2008;
Renvert & Persson 2009; Chrcanovic et al.
2014; Ramanauskaite et al. 2014).
Whereas periodontitis can be essentially
considered as a plaque-related disease,
patients with aggressive periodontitis show
some specific features: microbial deposits
inconsistent with severity of periodontal
breakdown, elevated proportions of A. actino-
mycetemcomitans and P. gingivalis, phago-
cyte abnormalities, and hyper-responsive
macrophage phenotype, including elevated
levels of prostaglandin E2 and interleukin IL-
1b (Demmer & Papapanou 2010; Kulkarni &

Table 6. Bone loss or the percentage of implants with peri-implantitis in relation to a history of periodontal disease
Bone loss in mm (% peri
Age range implantitis)
Study n patients (mean) or sub Follow-up
Authors design perio (yes/no) mean (perio year/n) mean (range) Type perio Perio Non-perio
Hardt et al. R 50 (25/25) (53.5, 57.3) 5 year # 2.2 1.7
(2002)
Karoussis et al. CCT 53 (8/45) NR 10 year # 1.0 (28.6%) 0.5? (5.8%)
(2003)
Rosenberg R 334 (151/183) NR (61.1, 49.5) 13 year # (25.6%) (5.4%)?
et al. (2004)
Mengel & CCT 39 (27/12) 1959 (32, 34, 31) 3 year Chron 0.9 0.7ns
Flores-de-
Jacoby (2005)
Aggr 1.1
Roos-Jans aker CCT 156 (94/62) NR 914 year # (9.2%) (2.2%)
et al. (2006c)
Mengel et al. CCT 17 (9/8) 1959 (34, 31) 3 year Aggr 0.9 0.5
(2007)
Gatti et al. CCT 62 (33/29) 3585 (56, 40) 5 year Moderate 2.7 1.2
(2008)
Severe 2.6
De Boever CCT 194 (84/110) 2080 (53) 4 year Chron 0.11/y 0.07/yns
et al. (2009)
Aggr 0.17/y
Matarasso R 80 (40/40) NR (46.5, 47.8) 10 year Chron 2.8 2.0
et al. (2010)
Simonis et al. R 55 (NR) 2988 (68.7) 1016 year # (37.9%) (10.5%)
(2010)
Aglietta et al. R 40 (20/20) NR (51) 10 year Chron 3.5 2.7
(2011)
Roccuzzo et al. CCT 101 (73/28) NR 10 year Moderate 1.1 (27.0%) 0.8ns (10.7%)
(2012)
Severe 1.0 (47.2%)
Swierkot et al. CCT 53 (35/18) (39.6, 38.6) 8.2 year (516) Aggr (26%) (10%)ns
(2012)
Roccuzzo et al. CCT 123 (91/32) NR (53, 43) 10 year Moderate (52.2%) (18.8%)
(2014)
Severe (66.7%)

NR, not recorded; CCT, controlled clinical trial; R, retrospective analysis; perio, periodontitis patients; non-perio, patients without a history of periodontitis;
#, no periodontitis classification; aggr, generalized aggressive periodontitis; ?, no statistical analysis on this parameter; ns, not significantly different.
*
Data in bold means statistically significant difference between # types of periodontitis.

28 | Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Kinane 2014). This group of patients also
have polymorphisms in genes regulating the
expression of IL-1, IL-6, IL-10, tumor necrosis
factor, E-selectins, Fc-g receptor, cluster of
differentiation 14, toll-like receptors, caspase
recruitment domain 15, vitamin D receptor,
lactoferrin, caldesmon, heat-shock protein 70
and Stac protein, and major histocompatibil-
ity complexes A9 and B15 (Stein et al. 2008;
Stabholz et al. 2010; Kulkarni & Kinane
2014). As a consequence of these polymor-
phisms, their inflammatory profile is altered,
including, but not limited to, polymorphonu-
clear neutrophil (PMN) trans-endothelial
migration and signaling (Gronert et al. 2004),
reduced chemotactic response, and depres-
sion in neutrophil phagocytosis and superox-
ide production (Nishimura et al. 1990).
In other words, in patients with chronic
periodontitis, proper plaque control and
smoking cessation will reduce the risk for
the recurrence of periodontitis and also for
peri-implantitis. In patients with a history of
aggressive periodontitis, the above-mentioned
risk indicators will remain, and as such, they
seem also more susceptible to peri-implanti-
tis. Monje et al. (2014) calculated that the
risk ratio for implant failures in patients with
aggressive periodontitis was significantly
higher when compared with patients without
a history of periodontitis (4.0) and those with
chronic periodontitis (3.97).
Genotyping
Although microorganisms are considered to
initiate the infection, the tissue breakdown
is mainly caused by the host response (Heitz-
Mayfield & Lang 2010). The production of
pro- and anti-inflammatory cytokines regu-
lates the inflammatory response to infection.
Cytokines are signaling substances that are
active in intercellular communication and
can be secreted by numerous cells of the
immune system. Pro-inflammatory cytokines
promote inflammation, whereas anti-inflam-
matory cytokines reduce the inflammatory
response. One factor reported to be of impor-
tance in the susceptibility to periodontal dis-
ease is genetic traits (Michalowicz et al.
2000). In case that the individual is geneti-
cally predisposed to overproduce pro-inflam-
matory cytokines, such as interleukin 1b (IL-
1b), interleukin 6 (IL-6), interleukin 17 (IL-
17), or tumor necrosis factor a (TNF-a), this
may result in an increase in tissue destruc-
tion. Accordingly, the individual host
immune response to the infection may be
related to the extent of alveolar bone loss. An
overexpression of several of the above-men-
tioned cytokines has also been reported in
2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Renvert & Quirynen
Risk indicators for peri-implantitis
peri-implantitis cases compared to healthy
implants (Javed et al. 2011). An increase in
IL-17, inducing the production of other pro-
inflammatory cytokines, has been demon-
strated in peri-implantitis (Severino et al.
2011). It has also been reported that the IL-1b
(+3954) gene polymorphism seems to affect
osseointegration (Cosyn et al. 2014). Genes
that control or modify aspects of the host
response may accordingly be considered as
risk factors for peri-implant infections.
Studies presenting data on the association
between peri-implantitis and genetic poly-
morphisms were included in this part of the
review.
Results
A total of 11 studies were selected from this
part of the review (Table 7). The data on
genetic markers associated with peri-implan-
titis are limited and initially focused on the
polymorphisms in the IL-1a and IL1-b geno-
types (Laine et al. 2006; Lachmann et al.
2007; Hamdy & Ebrahem 2011; Melo et al.
2012). Laine et al. (2006) in a group of 120
Caucasians, 71 of them presenting with a
diagnosis of peri-implantitis and 49 diagnosed
with healthy implants, reported IL-1RN gene
polymorphism to be associated with peri-im-
plantitis, especially in smokers. The frequen-
cies, however, of IL-1a (-889), IL-1b (-511),
and IL1-b (+3954) allele 2 genotypes did not
differ between peri-implantitis patients and
controls. Lachmann et al. (2007), in a limited
sample, found no effect of the genotype (IL1-
b (+ 3954) or IL-1a (-889)) on the associations
between peri-implant crevicular fluid volume
and concentrations of crevicular inflamma-
tory mediators. Similarly, no difference in
the concentration of IL-1b and IL-6 was
detected between individuals with healthy or
inflamed peri-implant tissues (Melo et al.
2012). On the contrary, Hamdy & Ebrahem
(2011) analyzing 25 cases with healthy
implants and 25 with a diagnosis of peri-im-
plantitis reported the combination of IL-1
allele 2 (IL-1a (-889) and IL-1b (+3954)) to act
as a risk indicator for peri-implantitis. When
investigating the association between inter-
leukin-6 G174C polymorphism and suscepti-
bility to peri-implant disease, the authors
reported that this genotype may be a com-
mon risk indicator for both chronic periodon-
titis and peri-implant diseases (Casado et al.
2013a). Kadkhodazadeh et al. (2012, 2013a,b)
in a group of around 200 Iranian individuals
out of which approximately 40 individuals
presented with peri-implantitis reported that
the CC genotype of IL17 polymorphism
(rs10484879), a polymorphism of the (osteo-
29 |
protegerin) OPG gene (G1181C), and the CT
genotype of rs9533156 RANKL gene polymor-
phism may be indicators for peri-implantitis.
A polymorphism of IL-17R did, however, not
seem to affect the incidence of peri-implanti-
tis (Kadkhodazadeh et al. 2013c). In an early
paper by Cury et al. (2009) evaluating the
relationship between TNFa (-308) and peri-
implantitis, the authors reported that a poly-
morphism in allele 2 of TNFa (-308) did not
indicate an increased risk of peri-implantitis.
However, in a recent publication evaluating
the possible association between CD14-159
C/T and TNFa -308 A/G single nucleotide
polymorphisms with peri-implantitis in a
population of 369 Caucasian individuals,
both polymorphisms were found to be associ-
ated with peri-implantits (Rakic et al. 2014).
Discussion
It is well known that the inflammatory reac-
tion to infection varies between patients and
that this may be related to the individual
inflammatory response to the biofilm. It has
also been highlighted elsewhere in this paper
that patients having a history of periodontal
disease or who lost their teeth due to peri-
odontal disease are more likely to be affected
by peri-implant diseases. Although controver-
sies exist in the literature in regard to the
possible impact of Il-1 gene polymorphisms
and peri-implantits, some papers reported
such an association especially in heavy
smokers. Feloutzis et al. (2003) reported sig-
nificant differences for alveolar bone loss
(P < 0.04) between non-smokers and heavy
smokers for the IL-1 genotype-positive group
but not for the IL-1 genotype-negative group.
Gruica et al. (2004) reported that IL-1A and
IL-1B genotype-positive and heavy smokers
were at higher risk for the development of
inflammatory complications and increased
peri-implant marginal bone loss in compari-
son to non-smokers, and in the paper by La-
ine et al. (2006), the IL-1RN gene
polymorphism was associated with peri-im-
plantitis, especially in smokers.
When it comes to evaluating the potential
impact of different polymorphisms on the
susceptibility of peri-implantits, it should be
noticed that the majority of the studies cited
above are reporting data from small-sized
populations and that several of the cited
papers most likely represent the same patient
material (Kadkhodazadeh et al. 2012, 2013a,
b,c). The differences in the results regarding
the possible impact of the TNFa -308 A/G
single nucleotide polymorphisms on peri-im-
plantitis reported by Rakic et al. (2014) and
Cury et al. (2009) may be related to the dif-
Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544
Renvert & Quirynen
Risk indicators for peri-implantitis

Table 7. Gene polymorphism as risk indicator peri-implantitis clinical studies

Gene
polymorphisms Methodology/
Study Subjects studied Purpose of study Parameters assessed Results Comments
Laine et al. 120 North IL1B (+ 3953) To investigate the IL-1 Mouthwash samples Significant differences IL-1RN gene
(2006) Caucasian IL1A (-889) gene cluster were used for were found in the polymorphism is
individuals IL-1B(-511) polymorphisms in genotyping of the carriage rate of allele 2 associated with peri-
49 Individuals IL-1RN patients with peri- bi-allelic in the IL-1RN gene implantitis and may
with healthy implantitis polymorphisms IL-1A between peri- represent a risk
peri-implant (-889), IL-1B(+3953), implantitis patients and indicator for this
conditions IL-1B(-511), and a controls disease
71 peri- variable number of Logistic regression
implantitis tandem repeat IL- analysis taking smoking,
1RN gene gender, and age into
polymorphisms account confirmed the
using PCR technique association between the
IL-1RN allele 2 carriers
and peri-implantitis (OR
3; 95% CI 1.27.6;
P = 0.02)
Lachmann 29 implant IL1B (+ 3954) To assess relationships For determination of In patients with an In this limited sample, no
et al. (2007) maintenance IL1A (-889) between peri-implant the patients IL-1 implant affected from effect of genotype on
patients crevicular fluid volumes, genotype, a peri-implantitis, no the associations
18 individuals biochemical markers of commercial [PCR] kit statistically significant between peri-implant
with healthy the peri-implant was used influence of the crevicular fluid volume
peri-implant immune response, and A sweep was taken periodontitis-associated or concentrations of
conditions periodontitis associated from the mucosal genotype around the crevicular inflammatory
11 peri- genotype surfaces of the fixture can be stated mediators and
implantitis buccal plane with a genotype could be
cotton stick and found
sent for processing
Cury et al. 90 subjects TNFa (-308) To investigate the Clinical study Polymorphism in allele 2 Polymorphism in allele 2
(2009) 41 subjects with relationship between a Epithelial cells were of TNFa (-308) was not of TNFa (-308) did not
healthy implants specific polymorphism collected from the associated with peri- indicate an increased
(Group 2) in the TNFa gene (allele oral mucosa and implantitis (P = 0.8) risk for peri-
49 subjects with 2 of TNFa(-308)) and were used for implantitis
peri-implantitis peri-iimplantitis genotyping by the
polymerase chain
reaction technique

Gene
Number of polymorphisms Methodology/
Study patients/implants studied Purpose of study Parameters assessed Results Comments
Hamdy & 25 subjects with IL1B (+ 3954) To assess a Clinical study 17 individuals from the peri- The combination of IL-1
Ebrahem (2011) healthy implants IL1A (-889) possible Epithelial cells were implantitis patients and 5 allele 2 (IL-1A(-889) and
(Group 2) association of IL- collected from the patients from group of IL-1B(+3954)) in patients
25 Subjects with 1 allele 2 (IL-1A(- oral mucosa by individuals with healthy peri-implant tissues acts
peri-implantitis. 889) and IL-B plastic spatula and implants were genotype as a risk indicator for
(Group 1) (+3954) were used for IL-1 positive, with a statistically tissue destruction
genotypes with genotyping by the significant difference noted Genotype-negative
the severity of polymerase chain between the 2 groups patients demonstrated
peri-implantitis reaction technique Group I genotype-positive better response to
patients presented with treatment than
higher scores of clinical genotype-positive
parameters from peri- patients
implant sites compared
with group II; (P < 0.05)
Melo et al. 47 subjects IL1B (+ 3954) IL1B To evaluate Clinical study There was no significant The authors did not find
(2012) 31 with (-511) interleukin-1b Cells from buccal difference in the any significant
healthy implants IL6 (-174) and interleukin- mucosa were concentration of IL-1b and difference in the
16 with 6 concentration collected and their IL-6 detected between concentration of IL-1b
peri-implantitis in the crevicular genomic DNA groups and IL-6 between
fluid, and the extracted for The studied gene groups
impact of gene identification of polymorphisms had no Few individuals
polymorphisms polymorphisms: influence on peri-implant included
on healthy and IL1B+ 3954, IL1B - disease
diseased 511, and IL6 -174.
implants in
comparison with
healthy teeth

30 | Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
 Renvert & Quirynen
Risk indicators for peri-implantitis

Table 7. (continued)
Gene
Number of polymorphisms Methodology/
Study patients/implants studied Purpose of study Parameters assessed Results Comments
Kadkhodazadeh 206 individuals OPG 950C/T To investigate the Venous blood was A significant difference was The result indicate that
et al. (2012) 89 healthy OPG 1181G/C relationship obtained and detected regarding the a polymorphism of the
40 peri- between genomic DNA was G1181C polymorphism the OPG gene (G1181C)
implantitis osteoprotegerin extracted using CC genotype had may be associated with
77 chronic (OPG) gene Millers Salting Out significantly higher an increased risk for
periodontitis polymorphisms technique. The DNA occurrence in the peri- peri-implantitis
and chronic was analysed using implantitis group compared
periodontitis a DNA extraction kit to healthy and periodontal
and peri- and analysed using group (P < 0.05)
implantitis in an PCR technique
Iranian
population
Casado et al. 103 individuals IL-6 G174C To investigate the DNA was extracted Individuals with GG This genotype may be a
(2013a) 52 healthy association from buccal cells, genotype and allele G were common risk indicator
20 peri-implant between and the IL-6 G174C 1.53 and 1.43 times more for both Chronic
mucositis interleukin-6 (IL- polymorphism was susceptible to peri-implant periodontitis and Peri-
31 peri- 6) G174C genotyped by disease respectively implant diseases
implantitis polymorphism polymerase chain The frequency of the
and reaction-restriction genotype IL-6 174GG and
susceptibility to fragment length allele G may be a risk
peri-implant polymorphism indicator for peri-implantit
disease (PID) disease
and/or chronic
periodontitis
Kadkhodazadeh 197 individuals IL-17 To evaluate Venous blood was A significant difference was The CC genotype of IL17
et al. (2013a) 84 healthy whether the obtained and detected between the polymorphism
38 peri- polymorphism of genomic DNA was three groups in terms of (rs10484879) may
implantitis IL-17 gene plays extracted using the specific SNP studied contribute to the
75 chronic a role in chronic Millers Salting Out (P = 0.00) pathogenesis of peri-
periodontitis periodontitis technique. The DNA implantitis and
and peri- was analysed using periodontitis
implantitis the Kbioscience
competitive allele-
specific PCR
technique
Kadkhodazadeh 206 Individuals RANKL To investigate the Venous blood was Comparison of genotype CT genotype of
et al. (2013b) 89 healthy (rs9533156) association of obtained and expression of SNP rs9533156 RANKL gene
40 peri- RANKL (RS RANKL gene genomic DNA was rs9533156 on RANKL gene polymorphism was
implantitis 2277438) polymorphisms extracted using between the peri- significantly associated
77 chronic (rs9533156 and Millers Salting Out implantitis group with with peri-implantitis,
periodontitis rs2277438) with technique. The DNA chronic periodontitis and and may be considered
chronic was analysed using control groups revealed as a genetic indicator
periodontitis the Kbioscience statistically significant for peri-implantitis
and peri- competitive allele- differences (P = 0.001); the
implantitis in an specific PCR prevalence of CT genotype
Iranian technique was significantly higher
population amongst the chronic
periodontitis group
Kadkhodazadeh 193 individuals IL-17R To investigate the Venous blood was No significant differences Polymorphism of IL-17R
et al. (2013c) 83 healthy association of IL- obtained and between periodontitis, do not seem to affect
37 peri- 17R gene genomic DNA was peri-implantitis with AA, the incidence of peri-
implantitis polymorphism extracted using GG, GA genotype of IL-17R implantitis
73 chronic (rs879576) with Millers Salting Out gene (P = 0.8239)
periodontitis chronic technique. The DNA
periodontitis was analysed using
and peri- the Kbioscience
implantitis in an competitive allele-
Iranian specific PCR
population technique
Rakic et al. 369 Southeastern CD14 (-159) C/T To investigate Genotyping was Analysis of CD14-159 C/T CD14-159 C/T and TNFa -
(2014) Europe TNFa (-308) A/G whether performed using polymorphism showed that 308 A/G polymorphisms
Caucasians CD14-159 C/T polymerase chain genotype of CC nucleic acid were associated with
180 peri- and TNFa -308 reaction from the combination was associated peri-implantitis and
implantitis A/G single periphery blood with peri-implantitis (a may act as a risk
189 healthy peri- nucleotide samples fivefold increased risk) indicator for peri-
implant tissues polymorphisms For TNFa -308 A/G implantitis
are associated polymorphisms, AG
with peri- genotype was associated
implantitis with peri-implantitis (a
fivefold increased risk)

2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 31 | Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544
Renvert & Quirynen
Risk indicators for peri-implantitis

ferences in the sample size. The above-men-
tioned discrepancies between studies high-
light the limitations from the existing
research, making it difficult to draw any firm
conclusions from this part of the review.
Although genetic traits may influence the
inflammatory response and accordingly may
be an important risk indicator for peri-im-
plantitis, available data on the relationship
between peri-implantitis and genetic traits
are at present unclear. A great variation of
polymorphisms has been studied with con-
flicting results limiting the possibility to
draw conclusions on the importance of
genetic traits as risk factor for peri-implanti-
tis. The current data do not support genetic
testing to assess the risk of peri-implantitis.
Smoking as a risk factor for peri-implantitis
Smoking impairs various aspects of the innate
and adaptive host responses (Ryder et al.
1998a,b; Palmer et al. 2005; Ryder 2007).
Smokers also present with elevated total
white blood cell and granulocyte counts
(Smith et al. 2003), polymorphonuclear leuko-
cyte viability (Guntsch et al. 2006), superoxide
and hydrogen peroxide generation, and inte-
grin expression (Ryder 2007) as well as prote-
ase inhibitor production (Persson et al. 2001).
The humoral immune response is also
impaired by smoking (Graswinckel et al.
2004; Apatzidou et al. 2005). It has also been
demonstrated that tobacco smoke inhibits
the proliferation and/or function of B and T
cells (Sopori & Kozak 1998). Nicotine is the
most widely studied component of tobacco
for its effect on various cell populations in
the periodontium. In the gingival crevice
fluid of smokers, nicotine concentrations are
nearly 300 times those found in plasma
(20 ngml) (Ryder et al. 1998a). Gingival blood
and gingival crevice fluid flow increase as
early as 35 days following smoking cessa-
tion (Morozumi et al. 2004). This finding,
together with the observation that bleeding
upon probing increases following cessation
(Nair et al. 2003), supports a suppressive
impact of chronic smoking on gingival blood
flow and vascularity. There are several stud-
ies that have identified that nicotine has
properties that may impair wound healing
(Tipton & Dabbous 1995; Tanur et al. 2000;
Gamal & Bayomy 2002; Carvalho et al. 2006;
Cesar-Neto et al. 2006).
Studies comparing the subgingival microbi-
ota in smokers and non-smokers have yielded
conflicting results (Eggert et al. 2001; Haffa-
jee & Socransky 2001; Socransky & Haffajee
2005). Several studies have associated smok-
ing with periodontitis, tooth loss, dry socket,
and impaired wound healing after surgery
(Johnson & Bain 2000; Kornman & Robertson
2000; Scabbia et al. 2001; Sham et al. 2003;
Baljoon et al. 2004; Millar & Locker 2007;
Warnakulasuriya et al. 2010).
Data from studies evaluating the effect of
smoking on implant survival clearly demon-
strate that smoking has a negative effect (for
review see Table 8). The data suggest that
individuals, who smoke before or after implan-
tation, might suffer an approximately 35% or
70% higher risk of dental implant failure, as
compared to non-smokers. This statement is
in agreement with several systematic reviews
(Hinode et al. 2006; Strietzel et al. 2007; Chen
et al. 2013; Sgolastra et al. 2015). No statisti-
cally significant difference was found in com-
plications between non-smokers and past
smokers (Schwartz-Arad et al. 2004), indicat-
ing that the risk of complications can be
reduced up to the normal non-smoker com-
plication rate when smoking ceases.
Prospective studies with data on the inci-
dence of peri-implantitis for both smokers (S)
and non-smokers/former smokers (NS/FS) as
subpopulations were included.
Results
Nine prospective clinical trials reported on
differences in the incidence of peri-implanti-
tis between S and NS/FS (Table 9). The fol-
low-up time was considerable (often above
5 years). In all but one study, the smoking
group showed higher incidences of peri-im-
plantitis, but in only two studies, this differ-
ence reached statistical significance. In only
one study, a distinction was made between
non-smokers and former smokers but with-
out clear differences.
Discussion
The relationship between smoking and peri-
implantitis is controversial, as more identi-
fied studies have failed to find significant
differences in peri-implantitis incidence

Table 8. Incidence (in percentage) of implant failure (early and late together) in smokers and non-smokers or former smokers considering only pro-
spective studies with clear data on implant survival. If available, additional data (on bone loss or the percentage of implants with peri-implantitis)
was also considered
Bone loss in mm
% implant failure rate (% peri
(total number inserted implants) implantitis)
n patients Age range or Follow-up
Authors (NS/S) mean mean NS/S mean (range) NS/FS S NS/FS S
Bain (1996) 78 (NR) NR NR 5.7% (176) 19.1% (47)
Lindquist et al. (1997) 45 (24/21) 3364 year (NR) 10 year 2.2% (139) 0% (125)? 0.7 1.3
De Bruyn et al. (1999) 23 (13/10) NR 7 year 28.1% (32) 20.0% (30)ns
Grunder et al. (1999) 74 (55/19) 57.8 year  15.2 34 month 1.8% (164) 0% (55)?
Lambert et al. (2000) 662 (463/199) 3089 year 3 year 6.0% (1928) 8.9% (959)
Olson et al. (2000) 29 (NR)G 56 year  12 38.2 month 1.5% (65) 3.9% (51)?
Schwartz-Arad et al. (2000) 43 (NR)IP 47 year 5 year 10.0% (50) 16.7% (6)?
Widmark et al. (2001) 36 (25/11)G NR 35 year 10.7% (131) 38.8% (67)?
Kumar et al. (2002) 461 (389/72) NR 18 month 1.6% (914) 3.0% (269)ns
van Steenberghe et al. (2002) 339 NR 50 year  14 6 month 1.7% (1107) 5.1% (156)
Karoussis et al. (2003) 53 (41/12) NR 10 year 3.6% (84) 7.1% (28)ns
Hallman et al. (2005) 20 (11/9)G 4869 year (62) 3 year 8.0% (50) 41.4% (29)
Peleg et al. (2006) 731 (505/226)G 4281 year (53) 69 month 1.9% (1505) 2.6% (627)ns
Sanna et al. (2007) 30 (17/13)IL 3874 year (56) 2.2 year 0.8% (119) 8.3% (96) 1.2 2.6?
Levin et al. (2008) 64 (54/10) 1878 year (45) 6.1 year 5.6% (54) 10.0% (10)? 0.3 0.6
Tawil et al. (2008) 90 (50/40)IL,G 64.7 year 42.4 month 0.8% (254) 2.0% (245)?
Romanos et al. (2013) 20 (12/18)IL 65.9/55.5 63/98 month 1.0% (97) 3.0% (66)ns 0.4 0.5ns
DHaese et al. (2013) 26 (17/9)IL 2081 (52) 1 year 1.3% (75) 30.8% (39) 0.4 0.6ns
Cha et al. (2014) 161 (143/18)G 2263 (NR) 57.1 month 0% (414) 14.6% (48)

ns, not significantly different; ?, no statistical analysis on this parameter.

Data in bold means statistically significant difference between NS/FS and S.

32 | Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Table 9. Incidence (in percentage) of peri-implantitis in smokers and non-smokers or former smokers considering only prospective studies
Authors n patients (NS/S)
Karoussis et al. (2003) 53 (41/12)
Roos-Jans
aker et al. (2006c) 218 (161/57)
Simonis et al. (2010) 55 (46/9)
Dvorak et al. (2011) 177 (NR)
Costa et al. (2012) 80
Swierkot et al. (2012) 53 (39/14)
Stoker et al. (2012) 94 (59/34)
Casado et al. (2013b) 215 (194/21)
Marrone et al. (2013) 103 (83/20)
PPD, pocket probing depth; BOP, bleeding upon probing; BL, bone loss; S, Smoker; NS, NonSmoker; FS, former smoker; ns, not significantly different; ?, no
statistical analysis on this parameter.
*Data on a patient level, data in bold means statistically significant difference between NS/FS and S.
between smokers and non-smokers (Karoussis
et al. 2003; Simonis et al. 2010; Dvorak et al.
2011; Costa et al. 2012; Stoker et al. 2012; Ca-
sado et al. 2013b; Marrone et al. 2013). Only
in two papers, a statistical difference was
reported between smokers and non-smokers
(Roos-Jansaker et al. 2006c; Swierkot et al.
2012). In a retrospective study by Rinke et al.
(2011), peri-implantitis was clearly found to be
associated with smoking (OR: 31.58;
P > 0.001). Another recent retrospective paper
evaluating 172 individuals with peri-implanti-
tis and 98 individuals with peri-implant health
smoking did not significantly contribute to
the outcome (Renvert et al. 2014). Thus, the
available information on the risk of smoking
in regard to peri-implantitis is insufficient to
identify smoking as a risk factor for peri-im-
plantitis.
Maintenance therapy of individuals supported
with dental implants
Peri-implantitis has been reported as a fre-
quent finding in patients without a struc-
tured maintenance program (Roos-Jans aker
et al. 2006b). Supportive periodontal therapy
consists of professional plaque control and
sub-gingival instrumentation at selected sites
showing clinical signs of inflammation, dur-
ing recall visits scheduled according to indi-
vidual needs (Lang & Tonetti 2003). In
patients treated with dental implants, it is
considered important, in order to prevent dis-
ease development, to involve such individu-
als in a structured maintenance program.
In this part of the review, papers reporting
on the association between maintenance care
and peri-implantitis were included.
Results
Studies evaluating the effect of maintenance
therapy are presented in Table 10. Several
2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Age range or
mean NS/S Definition PI
NR PPD 5 mm + BOP + BL
Success: BL <0.2 mm/year
65.6 year BL 3 threads between year 1
and follow-up + BOP + Pus
68.7  12
63 year BOP + Pus +PPD >5 mm + BL
PPD 5 mm + BOP + BL
8.2 (516) PPD >5 mm + BL >0.2 mm/year
59.8 year PPD >6 mm + BL 3 mm
55  12.5 BL >1 mm year 1 & >0.2 mm/year
62 (2686) PPD >5 mm + BOP + BL >2 mm
longitudinal studies have demonstrated that
patients who do not comply with a struc-
tured maintenance program more frequently
develop peri-implantitis compared to compli-
ant patients (Roccuzzo et al. 2010, 2012,
2014; Rinke et al. 2011; Costa et al. 2012;
Pjetursson et al. 2012b).
Discussion
The aim of a maintenance program is to
maintain implant health. Such a mainte-
nance program should be individually based,
taking into account both local- and patient-
related risk factors. The patients previous
history of periodontal disease must accord-
ingly be accounted, and factors like the loca-
tion and soft tissue seal around the implants
and the prosthetic design may, for example,
influence the patients ability to perform an
adequate oral hygiene. To be able to properly
clean the implant, the prosthetic design must
allow for adequate oral hygiene measures. It
is important to underline that the patient
needs to be motivated to comply with the
maintenance program and to the instructions
given by the dental personnel in order to
maintain implant health.
The data from the studies by Roccuzzo
et al. (2010, 2012, 2014) basically evaluate
the same patient group, and they support the
concept that an individually based supportive
therapy regimen in individuals with dental
implants reduces the number of biological
complications. Also, Costa et al. (2012)
reported that the absence of preventive main-
tenance was significantly associated with
peri-implantitis (OR 5.92) even if the mean
number of visits during the follow-up period
in the maintenance group was low (mean
5.6  0.3 visits per year). It has been demon-
strated that implants placed in patients with
33 |
Renvert & Quirynen
Risk indicators for peri-implantitis
% peri-implantitis (total number
inserted implants)
Follow-up
mean (range) NS&FS S
10 year 9.5% (8/84) 17.9% (5/28)ns
77.4% 64.3%ns
914 year 2.8% (19/684) 15.5% (47/303)
16.5% 23.5%ns
6 year (124) No statistical difference S vs.
NS&FS
5 year No statistical difference FS vs. NS
8.2 year (516) Significantly > in S and FS
8.3 year 1.7% (1/59)* 11.4% (4/35)*,?
18 year 40.2% (78/194)* 38.1% (8/21)*,ns
8.5 year 30.3% 38.5%ns
a previous history of periodontitis attending a
regular maintenance program demonstrated
stable clinical and radiographic results over a
period of 10 years (Meyle et al. 2014). More-
over, if individuals surgically treated for peri-
implant disease are involved in a structured
maintenance program, it has been demon-
strated that the treatment results initially
obtained as a result of therapy can be main-
tained for a period of 5 years (Roos-Jans aker
et al. 2014; Serino et al. 2014).
General diseases as a risk factor for peri-
implantitis
The association between periodontal diseases
and general diseases has attained a great
interest during the last decade. Following
the joint EFP/AAP workshop on periodonti-
tis and general diseases, it was concluded
that (i) there is consistent and strong epi-
demiologic evidence that periodontitis
imparts increased risk for future cardiovas-
cular disease (Tonetti & Van Dyke 2013)
and (ii) that severe periodontitis adversely
affects glycaemic control in diabetes and
glycaemia in non-diabetes subjects. In diabe-
tes patients, there is a direct and dose-depen-
dent relationship between periodontitis
severity and diabetes complications (Chap-
ple & Genco 2013). Based on the available
evidence on the association between peri-
odontal disease and general diseases, it
therefore seems logical to anticipate that
these general diseases could also influence
the development of peri-implantitis. In a pre-
vious review on risk factors for peri-implan-
titis by Heitz-Mayfield (2008), it was
highlighted that there is limited evidence
that there is an association between peri-
implant diseases and common systemic dis-
eases. Only one study suggested, after using
Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544
Renvert & Quirynen
Risk indicators for peri-implantitis

Table 10. Lack of supportive therapy as a risk indicator for peri-implantitis

Provided SPT- Evaluation
Study Subjects Purpose of Study intervals period Results Comments
Roccuzzo 101 patients To compare the long- An individually 10 years Statistically significant Although not discussing
et al. (2010) 28 Periodontal term outcomes of tailored difference in the peri-implantitis there is
healthy implants placed in maintenance care number of patients a clear indication of
37 with moderate patients treated for program (SPT) with sites with bone the importance of
PD periodontitis If a patient loss >3 mm (P = 0.003) maintenance care in
36 with Severe PD periodontally expressed the desire and for implant loss preventing loss of bone
4 Healthy, 11 compromised patients not to attend (P = 0.005) between around implants
Moderate PD and in periodontally follow-up subjects adhering and
7 Severe PD did not healthy patients in examinations, he/ not adhering to SPT
attend the relation to adhesion to she was classified as
supportive supportive periodontal dropout
periodontal therapy therapy
(SPT) visits
Rinke et al. 89 patients To evaluate of the 3-month intervals 5 years Statistical analysis Patients not regularly
(2011) prevalence rates of peri- during the first year identified a significant attending
implant mucositis and and then in 6- association of peri- Prophylaxis/SPT had a
peri-implantitis in month intervals implantitis with 11-fold higher risk for
partially edentulous Patients with PI compliance (OR:0.09; peri-implantitis
patients in a private >35% were seen at P = 0.011) compared to patients
dental practice 3-month intervals with a good
until PI <20% was compliance
established for three
consecutive SPT0 s
Corbella 61 Patients with full To assess the outcomes Scheduled for follow- 6 months to Systematic hygienic The SPT protocol
et al. (2011) arch rehabilitation of an implant up visits every 5 years protocol was effective followed was useful to
maintenance protocol 6 months for (Mean in preventing peri- prevent peri-implant
for implants supporting +2 years, then yearly 18.3 months) implant mucositis as inflammatory disease
a full-arch up to 4 years well as in controlling and to reduce plaque
rehabilitation plaque accumulation accumulation and
and clinical attachment bleeding on probing
loss The absence of a
control and the
relatively low sample
size at later follow-up
visits are main
limitations of this
study
Costa et al. 80 individuals To determine the The maintenance 5 years The incidence of peri- The absence of
(2012) 39 received incidence of peri- group received at implantitis in the preventive maintenance
preventive implantitis in least five dental maintenance group in individuals with pre-
maintenance individuals with visits during the was 18% compared to existing peri-implant
41 did not receive mucositis in a 5-year evaluation period; 43.9% in the group mucositis was
maintenance follow-up study (mean: 5.6  0.3) that did not receive associated with a high
maintenance incidence of peri-
implantitis
The incidence of peri-
implantitis was high in
both groups.
Approximately only 1
visit per year in the
maintenance
group
Pjetursson 70 Patients To assess the long-term Only reported as 323 years In patients attending a The prevalence of peri-
et al. 47 had SPT care ta a survival of implants well-organized and (Mean well-organized and implantitis was lower in
(2012b) University clinic inserted in regularly performed 7.9 years) regularly performed SPT the group that was in a
23 referred back to periodontally SPT at the at the University, 31.9% well organized SPT at
private practice susceptible patients and University of the patients had one the University
to investigate the or more implants
influence of residual affected by peri-
pockets on the implantitis (definition
incidence of peri- of PPD >5 mm and BOP
implantitis and implant positive) or lost due to
loss peri-implantitis
compared with 52.2%
of the patients that
were referred back to
the referring
practitioners for SPT.
The difference did not
reach statistical
significance (P = 0.102)

34 | Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
 Renvert & Quirynen
Risk indicators for peri-implantitis

Table 10. (continued)

Provided SPT- Evaluation
Study Subjects Purpose of Study intervals period Results Comments
Roccuzzo 101 patients To compare the long- An individually 10 years A significant difference The data support the
et al. (2012) 28 Periodontal term outcomes of tailored was found between concept of an
healthy implants placed in maintenance care moderate PD patients individually based
37 with moderate patients treated for program (SPT) adhering and not supportive therapy
PD periodontitis If a patient adhering to SPT, regimen in individuals
36 with Severe PD periodontally expressed the desire PI 25  2.7% vs. with dental implants
4 Healthy, compromised patients not to attend 38.5  4.8%; The patients previous
11 Moderate PD and in periodontally follow-up (P = 0.011), history of periodontal
7 Severe PD healthy patients in examinations, he/ BOP 23  2.7% vs. disease must be
did not attend the relation to adhesion to she was classified as 50  4.9%; accounted for in
supportive supportive periodontal dropout (P = 0.0001) designing such a
periodontal therapy therapy and PD 3.2  0.6 vs. maintenance
(SPT) visits 4.3  1.2; program
(P = 0.008).
A significant difference
was found between
individuals in the severe
group adhering and not
adhering to SPT
PI 20.3  2.4%
vs.39.6  7.1%;
(P = 0.003)
BOP 27.2  2.7% vs.
52.1  7.2%:
(P = 0.0006)
Roccuzzo 123 patients To compare the long- An individually 10 years The differences between In individuals without a
et al. (2014) 32 Periodontal term outcomes of tailored patients adhering or previous history of
healthy implants placed in maintenance care not to the SPT were periodontitis attending
46 with moderate patients treated for program (SPT) statistically significant: an individualized SPT
PD periodontitis If a patient Moderate PD: program the biological
45 with Severe PD periodontally expressed the desire PI (P < 0.001), BoP complications at
13 Healthy, compromised patients not to attend (P = 0.018), deepest PD implants are low
21 Moderate PD and in periodontally follow-up at 10-year (P = 0.02)
14 Severe PD had an healthy patients in examinations, he/ and implants with at
inconsistent relation to adhesion to she was classified as least one site with PPD
attendance to the supportive periodontal dropout 6 mm (P < 0.001);
SPT or refused the therapy (SPT) Severe PD:
proposed additional Probing depth
treatment (P = 0.03), teeth lost
during SPT (P = 0.03),
deepest PPD at 10 year
(P = 0.01) and implants
with at least one site
with PD 6 mm
(P = 0.001)
Frisch et al. 236 patients To evaluate patient SPT were with 3- 3 years Patients with greater The data clearly
(2014) compliance rates and month recall distances to the study demonstrate the
influential factors intervals. centre showed positive effects of an
regarding a systematic Non-compliant decreased compliance SPT program
SPT program patients were rates Longer observational
during; There was a significant periods are needed to
Year 1; correlation between evaluate the effects of
13 patients (5.5%) d lower compliance and patient compliance on
Year, 2; increased PPD peri-implant disease
19 patients (8.1%), (P = 0.032) rates
Year 3; Individuals with lower
year, compliance rates
34 patients (14.4%). demonstrated with
4 patients (1.69%) higher plaque scores
did not have any but this correlation was
appointment during not significant
the observation (P = 0.087)
period,
Only 6 patients
showed complete
compliance with all
4 appointments per
year

2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 35 | Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544
 36 |
Table 11. Systemic conditions as a risk factor for peri-implantitis
Study Number of patients/implants Study Evaluation period Results Comments
Ferreira et al. 212 patients A cross sectional study to 6 months5 years Subjects with diabetes were Prevalence of peri-implantitis in subjects
(2006) 578 Implants investigate the prevalence and more susceptible to develop was 8.9% (n = 19)
risk variables of peri-implant peri-implantitis Presence of periodontitis and diabetes
disease were statistically associated with increased
risk of peri-implantitis
Renvert et al. 19 subjects and 80 implants A prospective study to study the 13 years The incidence of peri-implantitis Individuals with a history of periodontitis
(2012) with a tioblast surface incidence of peri-implantitis between years 1 and 13 was and with systemic disease were at higher
22 subjects with 84 implants over 13 years between two significantly related to a risk for future incidence of peri-
with a machined surface was types of dental implants and to diagnosis of periodontitis implantitis
assessed for the incidence of assess if microbiological results (P < 0.001), and not being Differences in implant design did not
peri-implantitis at year 7, smoking and systemically healthy (P = 0.024) influence the incidence of peri-implantitis
systemic health condi- tions over a 13 year period
could predict future incidence
of peri-implantitis

Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544

Daubert et al. 96 patients 225 implants A cross-sectional study to Mean follow up Peri-implantits was associated Peri-implantitis occurred in 16% of the
Renvert & Quirynen
Risk indicators for peri-implantitis

(2015) identify risk factors for implant
loss and peri-implant diseases
and to utilize those risk factors
to form a predictive model for
peri-implantitis and implant
loss
Renvert et al. 172 patients with peri- Retrospective study to assess the
(2014) implantitis likelihood that peri-implantitis
98 healthy/peri-implant was associated with general
mucositis patients diseases, periodontitis and
smoking habits
time 10.9 years with subjects with diabetes at
time of placement (RR 3.0,
95% CI 1.27.7)
Retrospective After adjusting for confounders
stud (age, smoking status, gender)
odds ratio of having peri-
implantitis and cardiovascular
disease was 8.7 (95% CI:2.8, 4.3
P < 0.001)
implants and 26% of the subjects
Peri-implantitis was associated with
individuals who were younger at time of
implant placement (RR 0.8 per 10 years of
age, 95% CI 0.61.0)
In relation to peri-implantitis a high
likelihood of comorbidity was expressed
by a history of periodontal disease and a
history of cardiovascular disease
Smoking or gender did not significantly
contribute to the outcome
Results

Discussion
3.0, 95% CI 1.27.7).
risk of peri-implantitis..

General Discussion
larger patient populations.
with a high prevalence of moderate plaque,

2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
This review concentrated on the inflamma-
dence available peri-implant, it may be
model linear regression including periodonti-

tional research is needed to verify this in

mann et al. (2013) demonstrated significant
short-term study including older individuals
ing, gender, and number of implants per
however, disappeared when employing a mul-
univariate analysis of data, that individuals

spectrum of the etiology of peri-implantitis

lar diseases and evidence of implants and
comorbidity in individuals with cardiovascu-
ated with dental implant complications and
diseases and peri-implantitis. However, one
with diabetes at the time of placement (RR
after adjusting for age, smoking status, and
viduals with and without peri-implantitis,
In a recent retrospective study comparing indi-
dence of peri-implantitis between years 1 and
subjects as covariates confirmed that the inci-

with periodontitis. Based on the limited evi-

including cardiovascular diseases were associ-
There are still limited data available regard-
of having peri-implantitis and cardiovascular
13 was significantly related to a diagnosis of
Four studies were analyzed regarding the asso-

periodontitis (P < 0.001) and not being system-

tis and health status as predictors with smok-
follow-up study, analysis by generalized linear
jects with diabetes were more susceptible to
a univariate analysis demonstrated that sub-
plantitis (Table 11). Ferreira et al. (2006) using

may be more complex. The group around Zarb

tory concept of peri-implantits, but the total
related to general diseases like diabetes mell-
ing possible associations between systemic
peri-implantits was associated with subjects
gender. Daubert et al. (2015) reported that
Renvert et al. (2014) concluded that odds ratio
with diabetes mellitus are at an increased

itus and cardiovascular diseases, but addi-

BOP, and the presence of bacteria associated
bone loss (Lee et al. 2010) and recently, Lach-
tivariate analysis of the data. In a longitudinal

has failed to show that systemic conditions

disease was 8.7 (95% CI: 2.8, 4.3 P < 0.001)
ically healthy (P = 0.024) (Renvert et al. 2012).
develop peri-implantitis. This association,
ciation between general diseases and peri-im-

has proposed three theories for peri-implanti-
tis: infection, occlusal overload, and/or a com-
promised healing/adaptation (Chvartszaid
et al. 2008; Chvartszaid & Koka 2011; Koka &
Zarb 2012). All three theories have degrees of
merit, and proponents and opponents.
The presence of suppuration, the isolation
of periodontal pathogens from failing
implants, and the beneficial effects of inter-
vention to reduce this burden lead to the
hypothesis that peri-implantitis is infectious
in nature (Mombelli et al. 1987; Mombelli &
Lang 1992; Leonhardt et al. 1999; Shibli et al.
2008; Heitz-Mayfield & Lang 2010; Persson
& Renvert 2014) (the infection hypothesis).
Several clinical studies have shown an associ-
ation between periodontal diseases (or abundant
plaque) and implant failure/peri-implantitis, but
this may be influenced by confounding factors
like the patients susceptibility to infection,
smoking habits, and the individuals general
health status. Plaque accumulation along
implants certainly leads to inflammatory
changes (Renvert & Polyzois 2014) that when
left untreated may result in marginal bone loss
(Heitz-Mayfield 2008; AAP White paper on Peri-
implantitis 2013). It is, however, possible that
implant failure can also result from other
causes.
Biomechanical overload at the bone/implant
interface has been hypothesized to be causative
of, or contributing to marginal bone loss (the
occlusal overload hypothesis). While some
mechanical strain at the implantbone inter-
face is regarded as desirable, strains beyond a
certain threshold can produce deformation of
the bone and an uncontrolled biologic response
with an implant loosening or the induction of a
fibrous connective tissue interface. The ques-
tion of whether or not occlusal load/overload
could be a contributing factor for peri-implanti-
tis remains unresolved. Some recent reviews
have considered occlusal overload as a contrib-
uting factor for peri-implantitis (Chambrone
et al. 2010; Fu et al. 2012); however, this view
is not undisputed (Hsu et al. 2012; Naert et al.
2012). Experimental studies have in fact failed
to induce the peri-implant bone loss caused by
occlusal overload (Gotfredsen et al. 2002;
Heitz-Mayfield et al. 2004). Although the evi-
dence for the impact of occlusal overload on
peri-implantitis is lacking, it seems advisable
to include an evaluation of the patients occlu-
sion during maintenance visits (Hsu et al.
2012; Merin 2014).
In the early loading phase, the cumulative
effect of all challenges to the interface func-
tional loading, plaque-induced inflammation,
2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Renvert & Quirynen
Risk indicators for peri-implantitis
and/or compromised ability to respond (e.g.
poor host response secondary to diabetes or
smoking) might lead to a degenerative pro-
cess to the point that it overwhelms the
implanthost system and becomes symptom-
atic (the compromised healing/compromised
adaptation hypothesis). Failures soon after
loading are indicative of a compromised heal-
ing response and/or one that produced an
interface that is unable to adapt to the func-
tional challenges (Chvartszaid et al. 2008).
In recent years, the pure infective nature of
peri-implantits has been questioned, and
other mechanisms for marginal bone loss
have been proposed (Qian et al. 2012). How-
ever, as of today, there is no evidence for
peri-implant bone loss in the absence of bio-
film formation. Obviously, an implant sur-
face harboring the biofilm becomes a trigger
mechanism for the host response, leading to
an inflammatory/infectious lesion.
Without doubt one can conclude that the eti-
ology of peri-implantitis is very complex. In
fact, a multi-causality model to explain peri-im-
plantitis could be applied as many risk indica-
tors are neither necessary nor sufficient to
produce disease by themselves and a joint
action of several risk factors may be needed to
result in disease. Removal of a single risk indi-
cator will accordingly not necessarily lead to
healing and prevention of the disease. Since
that, many factors might play a role in the
development of disease around dental implants
and a correct diagnosis of the etiology is nearly
impossible. In consequence, the outcome of the
peri-implantitis therapy may depend on the
management of several triggering factors.
Today the concept of total inflammatory
burden gains an increased acceptance. It sug-
gests that a patient can cope with a certain
amount of infection, but once a certain
threshold is overpassed, the pathogens seem
to overrule the immune response resulting in
tissue damage. It might therefore be wise to
reduce the general infectious burden in the
patient to a minimum, although this philoso-
phy still has to be explored and proven. Easy
factors to consider are as follows: cleansable
prostheses, improved oral maintenance, strict
supportive periodontal therapy schedule,
smoking cessation, and improved diet (e.g.
antioxidants). The outcome of treatment can
be completely different for patients affected
by systemic diseases or other compromising
factors compared to generally healthy indi-
viduals (Beikler & Flemmig 2003; Hwang &
Wang 2006; Mombelli & Cionca 2006; Pa-
quette et al. 2006; Bornstein et al. 2009; Ren-
37 |
vert et al. 2014). Metabolic anomalies or
immune deficiencies can, for example, give
rise to surgical complications and may also
interfere with bone apposition and/or remod-
eling at the implantbone interface.
The incidence of peri-implantitis seems to
be higher today, than what is was 20 years
ago. All factors discussed in this review can-
not explain this increase. The increase in the
number of implants placed per year is of
course an important factor. Another possible
explanation for the reported increase in peri-
implantitis cases may be related to a change in
the clinical protocol for the placement of oral
implants over the past 40 years (Quirynen
et al. 2014). The initial very strict biocom-
patibility protocol with long-term success as
ultimate goal has developed toward a less
strict protocol focusing on speed and
esthetics. Whether the patient benefits from
these changes is questionable.
Peri-implantitis and implant failures cluster
in subsets of individuals, and a patient who has
lost one implant is at elevated risk of experi-
encing other implant losses (Weyant & Burt
1993; Hutton et al. 1995; Chuang et al. 2005;
Roos-Jans aker et al. 2006a; Lee et al. 2014).
The cluster phenomenon of peri-implantitis
highlights that specific host characteristics,
including genetic factors, may play an impor-
tant role in the development of peri-implanti-
tis. There is to our knowledge no scientific
evidence for the etiology of clustering failure
phenomena. Therefore, future studies using
multi-variate analysis of the data are indicated
to determine risk factors. Proper treatment pro-
tocols for peri-implantitis patients also need to
be developed. Based on currently available evi-
dence, it seems reasonable to aim for a reduc-
tion in the infection and inflammatory burden
to minimize the risk of peri-implant diseases.
Conclusions
A cause and effect relationship has been
established for plaque accumulation at
dental implants triggering the inflamma-
tory host response resulting in peri-
implant mucositis/peri-implantitis.
Natural teeth may act as a reservoir for
pathogens colonizing implants.
The microbiota associated with peri-im-
plantitis is complex demonstrating differ-
ences and similarities to the one seen at
periodontitis sites.
Excess cement may be a contributing factor
to the development of peri-implantitis.
Clin. Oral Impl. Res. 26 (Suppl. 11), 2015 / 1544
Renvert & Quirynen
Risk indicators for peri-implantitis
Smoking is a risk indicator for peri-im-
plantitis.
Patients with a history of periodontitis
(especially aggressive periodontitis) are at
higher risk to develop peri-implantitis.
Successful treatment of periodontitis
prior to implant placement lowers the
risk for peri-implantitis.
Genetic polymorphisms may play a role
in the development of peri-implantitis
especially in heavy smokers.
Diabetes and cardiovascular diseases may
be associated with peri-implantitis.
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