Received: 6 June 2016 | Revised: 14 September 2017 | Accepted: 24 September 2017

DOI: 10.1111/jcpe.12954

2 0 1 7 W OR L D W OR K S HO P

Peri‐implantitis

Frank Schwarz1* | Jan Derks2* | Alberto Monje3,4 | Hom‐Lay Wang4

1
Department of Oral Surgery and
Implantology, Carolinum, Johann Wolfgang Abstract
Goethe‐University Frankfurt, Frankfurt, Objectives: This narrative review provides an evidence‐based overview on peri‐
Germany
2
im‐ plantitis for the 2017 World Workshop on the Classification of Periodontal and
Department of Periodontology, Institute
of Odontology, The Sahlgrenska Academy Peri‐ Implant Diseases and Conditions.
at University of Gothenburg, Gothenburg,
Methods: A literature review was conducted addressing the following topics: 1)
Sweden
3 defini‐ tion of peri‐implantitis; 2) conversion from peri‐implant mucositis to peri‐
Department of Oral Surgery and
Stomatology, ZMK School of implantitis, 3) onset and pattern of disease progression, 4) characteristics of peri‐
Dentistry, University of Bern, Bern,
implantitis, 5) risk factors/indicators for peri‐implantitis, and 6) progressive crestal
Switzerland
4
Department of Periodontics and Oral
bone loss in the ab‐ sence of soft tissue inflammation.
Medicine, University of Michigan School of Conclusions:
Dentistry, Ann Arbor, MI, USA
1) Peri‐implantitis is a pathological condition occurring in tissues around dental
Correspondence implants, characterized by inflammation in the peri‐implant connective tissue
Univ. Prof. Dr. Frank Schwarz, Department
and progressive loss of supporting bone.
of Oral Surgery and Implantology,
Carolinum, Johann Wolfgang Goethe‐ 2) The histopathologic and clinical conditions leading to the conversion from peri‐
University Frankfurt, 60596 Frankfurt,
implant mucositis to peri‐implantitis are not completely understood.
Germany.
Email: [email protected]‐frankfurt.de 3) The onset of peri‐implantitis may occur early during follow‐up and the disease
progresses in a non‐linear and accelerating pattern.
*Frank Schwarz and Jan Derks equally
contributed to the manuscript and are 4a) Peri‐implantitis sites exhibit clinical signs of inflammation and increased probing
considered joint first authors. depths compared to baseline measurements.

The proceedings of the workshop were

4b) At the histologic level, compared to periodontitis sites, peri‐implantitis sites
jointly and simultaneously published in often have larger inflammatory lesions.
the Journal of Periodontology and Journal of
Clinical Periodontology.
4c) Surgical entry at peri‐implantitis sites often reveals a circumferential pattern of
bone loss.
5a) There is strong evidence that there is an increased risk of developing peri‐
implantitis in patients who have a history of chronic periodontitis, poor plaque
control skills, and no regular maintenance care after implant therapy. Data
identifying “smoking” and “diabetes” as potential risk factors/indicators for peri‐
implantitis are inconclusive.
5b) There is some limited evidence linking peri‐implantitis to other factors such as:
post‐restorative presence of submucosal cement, lack of peri‐implant kerati‐ nized
mucosa and positioning of implants that make it difficult to perform oral hygiene
and maintenance.
6) Evidence suggests that progressive crestal bone loss around implants in the ab‐
sence of clinical signs of soft tissue inflammation is a rare event.

K E Y WO R D S
diagnosis, implantology, peri‐implantitis, systematic reviews and evidence‐based medicine

© 2018 American Academy of Periodontology and European Federation of Periodontology

S246 | wileyonlinelibrary.com/journal/jcpe

J Clin Periodontol. 2018;45(Suppl 20):S246–S266.

 SCHWARZ et Al . | S247

INTRODUCTION features or conditions characterizing the conversion from peri‐im‐

plant mucositis to peri‐implantitis have not been identified.
Biological complications affecting osseointegrated implants are The peri‐implant soft tissue reactions to plaque formation have
a topic of major interest in contemporary dentistry. Such compli‐ been extensively evaluated in both animal 6‒13 and human stud‐ ies.14‒16
cations mainly refer to inflammatory conditions associated with a Thus, plaque formation consistently resulted in an inflam‐ mation of
bacterial challenge.1‒3 Two clinical varieties may be distinguished: the peri‐implant soft tissues,14‒16 associated with clinical signs of
peri‐implant mucositis and peri‐implantitis. While the presence of inflammation, such as redness and edema.7
an inflammatory lesion is a feature both conditions have in com‐ Zitzmann et al. (2002) examined human biopsies after a plaque
mon, only the latter form presents with loss of supporting bone. 4 It formation period of 21 days. 13 The histologic analysis revealed the
is anticipated that mucositis precedes peri‐implantitis. 3 establishment of a B and T cell‐dominated inflammatory cell infil‐
This review addresses the following topics: 1) definition of peri‐ trate (ICT) in the soft tissue lateral to the barrier epithelium, occupy‐
implantitis; 2) conversion from peri‐implant mucositis to peri‐ ing an area of approximately 0.14 mm2,16
implantitis, 3) onset and pattern of disease progression, 4) Similar findings were made in animal studies, presenting with a
characteristics of peri‐implantitis, 5) risk factors/indicators for peri‐ varying apical extension of the inflammatory lesion.7,9,10,12 At most of
implantitis, and 6) progressive crestal bone loss in the ab‐ sence of the implant sites investigated, the lesion was located lateral to the
soft tissue inflammation. barrier epithelium and separated from the crestal bone by a zone
of healthy connective tissue. However, at some sites in one study,
the subepithelial connective tissue was infiltrated with inflammatory
METHODS cells (i.e. CD68 positive cells), thus decreasing the zone of healthy
connective tissue above the peri‐implant bone. 7 At 16 weeks of
Search strategy and data extraction plaque formation, the distance between the apical extension of the
ICT and the crestal bone varied between 1.0 and 1.9 mm. At only
An electronic and manual search was conducted for each of
one implant site did the ICT reach the crestal bone.7 The exact histo‐
the addressed topics. The PubMed database of the US National
pathologic mechanisms resulting in apical extension of the ICT and
Library of Medicine, the Excerpta Medica database (Embase) by
associated crestal bone loss have yet to be determined.
Elsevier, and the Web of Knowledge of Thomson Reuters were
Clinically, the conversion from mucositis to peri‐implantitis was
screened for relevant articles (i.e. experimental studies in ani‐
evaluated in one retrospective observational study including 80 pa‐
mals and humans/ observational studies, randomized/ controlled
tients initially suffering from peri‐implant mucositis. 17 Over 5 years,
clinical studies, systematic reviews/ meta‐analyses, consensus
the incidence of peri‐implantitis was lower in subjects enrolled in
reports). Data from identified and relevant publications were ex‐
a regular maintenance program (18%) than among patients without
tracted and, if indicated, presented in evidence tables. Overall
regular maintenance care (43%). In the “maintained” group, “BOP+
findings were summarized in a narrative manner.
at >50% of all implant sites” (OR 37) and “probing depth (PD) ≥4 mm
at >5% of sites” (OR 20) were associated with peri‐implantitis. In the
OBSERVATIONS AND DISCUSSION “not maintained” group, the associated factors were PD (OR 26) and
the presence of periodontitis (OR 11). In the entire patient group, the
Current definition of peri‐implantitis conversion to peri‐implantitis was correlated with BOP (OR 18) and
PD scores (OR 16), the lack of regular maintenance therapy (OR 6), as
Peri‐implantitis is a pathological condition occurring in tissues well as the presence of periodontitis (OR 9).
around dental implants, characterized by inflammation in the peri‐ The histopathologic and clinical conditions leading to the con‐
implant mucosa and progressive loss of supporting bone.1,4 version from peri‐implant mucositis to peri‐implantitis are not com‐
In the clinical setti ng, soft tissue inflammation is detected by pletely understood.
probing (bleeding on probing, BOP), while progressive bone loss
is identified on radiographs. Studies on peri‐implantitis require
case definitions and threshold values to distinguish 1) health Onset and pattern of disease progression
from disease and 2) mucositis from peri‐implantitis. It should be
noted that, while case definitions for peri‐implantitis vary con‐ Progression of experimentally induced peri‐implantitis
5
siderably between studies, the definition of the disease remains.
The so‐called “ligature model” is often used to study experimental
peri‐implantitis in animals.18,19 The protocol comprises a phase of active
tissue breakdown around osseointegrated implants, includ‐ ing
Conversion from peri‐implant mucositis to
plaque formation and placement of ligatures in a submucosal
peri‐implantitis
position.20 The ligature breaks the mucosal seal to the implant and
Mirroring the progression of gingivitis to periodontitis, peri‐im‐ promotes submucosal bacterial biofilm formation. The ensuing inflam‐
plant mucositis is assumed to precede peri‐implantitis. 3 Currently, matory lesion initiates tissue destruction, including bone loss. Also
 S248 | SCHWARZ et Al .

after the removal of the ligatures and under continuous plaque for‐ Becker et al. recently studied the incidence of biological complica‐
mation, progression of disease may occur. 22 This model thus mimics tions at zirconia implants over a 2‐year period in 52 patients.30 BOP
naturally occurring peri‐implantitis. When compared to experimen‐ values significantly increased from 21% at baseline (i.e. 10 to 12
tally induced periodontitis, lesions associated with experimental peri‐ weeks after implant placement) to 38% and 64% at 6 and 12 months,
implantitis demonstrate larger inflammatory cell infiltrates and more respectively. Based on the given case definition (BOP+ and changes in
rapid and pronounced bone loss. 21 After a period of several weeks the radiographic bone level compared to baseline), 18 patients were
of plaque formation subsequent to ligature removal, spontanoues diagnosed with initial peri‐implantitis between 12 and 24 months.30
progression of peri‐implantitis was associated with severe inflamma‐
tion and tissue destruction. 22 Disease progression was influenced by
implant surface characteristics with more pronounced breakdown at Characteristics of peri‐implantitis
21,23
implants with modified than with non‐modified surfaces.
Histopathologic characteristics of naturally occurring
peri‐implantitis
Clinical studies on onset and progression of peri‐
implantitis The histopathologic features of naturally occurring peri‐implan‐
titis lesions have been extensively assessed in human biopsy
Prospective studies evaluating onset and progression of naturally oc‐ materials.31‒39
curring peri‐implantitis could not be identified and are for obvious When compared with peri‐implant mucositis, the lesions at peri‐
ethical reasons not feasible. However, retrospective observational implantitis sites (case definition: BOP+, suppuration, radiographic
studies employing multilevel growth curve models provided statistical bone loss) harbored more neutrophil granulocytes and larger “pro‐
estimates on onset and pattern of peri‐implantitis associated bone portions of B cells (CD19+)”. 35 Similar to periodontitis, the lesions
24,25
loss. Fransson et al. evaluated 182 patients with a total of 419 im‐ at peri‐implantitis sites were also dominated by plasma cells and
plants (machined/turned surfaces, no bone grafting procedures, fixed lymphocytes,33,34,36 but characterized by larger proportions of poly‐
restorations) that presented with progressive bone loss. 25 For these morphonuclear leukocytes and macrophages.31,38 Recently, it was also
implants, bone levels were assessed using intra‐oral radiographs ob‐ shown that the size of peri‐implantitis lesions (case definition:
tained between the 1‐year examination and a follow‐up period of 5 to interproximal implant sites with BOP+ and PD ≥7 mm) was more
23 years (mean: 11.1 years). The average bone loss was 1.7 mm and than twice as large as that noted at periodontitis sites (3.5 mm2 vs.
cumulative percentages of implants with bone loss ≥1 mm, ≥2 mm, or 1.5 mm2).39 Moreover, peri‐implantitis lesions were characterized by
≥3 mm were 68%, 32% and 10%, respectively. A multilevel growth larger area proportions, numbers and densities of plasma cells,
curve model revealed that the pattern of bone loss was non‐linear, macrophages and neutrophils, as well as a higher density of vascular
accelerating and demonstrating an increased variance over time that structures outside and lateral to the cell infiltrate. 39 Another study
was attributed to subject heterogeneity. This was confirmed in a ret‐ using immunohistochemical analysis of harvested soft tissue biop‐
rospective analysis by Derks et al. 24 Results indicated that the onset sies showed that IL‐1α was a dominant osteoclast activating cytokine
of peri‐implantitis may occur early, as the majority of implants dem‐ at peri‐implantitis sites.37 It must be emphasized that the above anal‐
onstrated first signs of bone loss (>0.5 mm) already after the second yses of human peri‐implant tissue biopsies did, for ethical reasons,
(52%) and third year (66%) in function. 24 At the subject level, these not include the osseous component of the sites.
calculations amounted to 70% and 81%, respectively.
When evaluating the above studies, it must be kept in mind that
the onset of peri‐implantitis was estimated on the basis of radio‐ Microbiologic and immunologic characteristics
graphic bone loss alone, not considering other clinical parameters. 24,25 of naturally occurring peri‐implantitis
Nevertheless, these analyses suggest that peri‐implantitis may com‐ Using conventional DNA probe and cultural analyses, common perio‐
mence early during follow‐up and that the progression of peri‐implan‐ dontopathogenic bacteria have been isolated at both healthy and dis‐
titis appears to be faster than what is observed in periodontitis. 26‒28 eased implant sites,40 and the distribution of the detected species did
The concept of a potentially early onset of peri‐implantitis is fur‐ not markedly differ by clinical implant status (i.e. healthy, peri‐implant
ther supported by findings from studies evaluating peri‐implant mucositis, peri‐implantitis). 41 However, when compared with healthy
con‐ ditions already after comparatively short follow‐up periods (≤2 implant sites alone, peri‐implantitis was associated with higher
years). A cross‐sectional analysis of 238 patients with a total of 512 counts of 19 bacterial species, including Porphyromonas gingivalis and
implants revealed that peri‐implantitis (case definition: BOP+ and Tannerella forsythia.42 Moreover, observational studies have indicated
changes in radiographic bone level compared to baseline) was that peri‐implantitis was more frequently linked with opportunistic
frequently noted in all implant age groups investigated. 29 At the pathogens such as Pseudomonas aeruginosa and Staphylococcus
implant level, its fre‐ quency amounted to n = 18 at 1 to 12 months aureus (S. aureus),43,44 fungal organisms (e.g. Candida albicans, Candida
of follow‐up, n = 34 at 12 to 48 months and n = 12 at >48 months, boidi- nii, Penicillum spp., Rhadotorula laryngis, Paelicomyces
respectively. For the diagnosis of peri‐implant mucositis, the spp.),43,45,46 and viruses (i.e. human cytomegalovirus, Epstein‐Barr
number of affected implants in respective age groups was n = 25, n virus),47 thus point‐ ing to a rather complex and heterogenous
= 157 and n = 32, respectively. infection.48,49 It should be
 SCHWARZ et Al . | S249

emphasized that the submucosal microbiota of peri‐implantitis le‐ In this context, it must be realized that the determination of what
sions have not been extensively studied using culture‐independent constitutes a physiological PD at implant sites is difficult. A recent
techniques. Thus, the microbial picture associated with peri‐implanti‐ analysis described a high degree of variation in the vertical mucosal
tis should be regarded as incomplete. thickness measured at healthy implant sites, ranging from 1.6 to 7.0
Most recent systematic reviews have focused on the correlations mm (i.e. mucosal margin to the crestal bone level). 53 One cross‐sec‐
between various cytokines (i.e. proinflammatory/ anti‐inflamma‐ tional analysis also evaluated and compared the horizontal muco‐
tory/ osteoclastogenesis‐related) and chemokines measured in the sal thickness (hMT) at healthy and diseased implant sites. Median
peri‐implant crevicular fluid (PICF) and the clinical condition at im‐ hMT were significantly increased at diseased‐, when compared with
plant sites.50,51 Most of the included studies focused on the assess‐ healthy implant sites (1.1 mm), but were similar at mucositis and peri‐
ment of IL‐1β and tumor necrosis factor alpha (TNF‐α). Based on a implantitis sites (i.e. 1.7 vs. 1.6 mm), respectively. In all groups inves‐
meta‐analysis,50 the release of IL‐1β was reported to be significantly tigated, these values did not markedly differ by implant location (i.e.,
increased at mucositis and peri‐implantitis sites, when compared upper/lower jaws) or position (i.e., anterior/posterior sites).54
with healthy implant sites. However, no significant difference in IL‐1β Several consensus statements pointed towards suppuration as a
levels was noted between peri‐implant mucositis and peri‐implanti‐ common finding at sites diagnosed with peri‐implantitis. 1,4 One study
tis sites. Peri‐implantitis sites were also associated with a significant examined 197 implants in 97 patients demonstrating progressive bone
increase in TNF‐α levels over healthy implant sites.50 In contrast, the loss on radiographs.55,56 The authors compared these implants with 285
majority of included studies failed to identify any significant differ‐ implants in the same patients not exhibiting bone loss. It was ob‐
ences in the levels of either IL‐4, IL‐10, or osteoclastogenesis‐related served that, while 94% of the implants presenting with bone loss also
(RANKL) cytokines between healthy and peri‐implantitis sites.51 were positive for BOP, suppuration on probing was identified at 19%.
Accordingly, the systematic reviews indicated that the assessment Only 5% of implant sites without bone loss showed suppuration.
of proinflammatory cytokines (mainly IL‐1β) in the PICF might be of Clinical studies also reported on the configuration of peri‐im‐
beneficial value to differentiate between peri‐implant health and plantitis defects.57‒59 In 79% of all sites investigated, naturally oc‐
disease, but inappropriate to determine the onset of peri‐implantitis. curring peri‐implantitis lesions featured a combined supra‐ (Class
II) and intrabony (Class I) defect configuration. 58 The intrabony

Clinical characteristics of naturally occurring peri‐ component most frequently (55%) exhibited circumferential bone

implantitis loss with maintenance of the buccal and lingual contours of the
supporting crestal bone (i.e. Class Ie). This was followed by buc‐
Clinical signs of inflammation including redness, edema, mucosal en‐ cal dehiscence‐type defects revealing a semicircular defect to the
largement, BOP+ with or without suppuration along with increases middle of the implant body (i.e. Class Ib) (16%), and buccal dehis‐
in PD and radiographic bone loss are commonly used in case defini‐ cence‐type defects with circular bone resorption in the presence
tions for peri‐implantitis.31,33‒39 (i.e. Class Ic) (13%), or absence (i.e. Class Id) (10%) of the lingual
Implant sites diagnosed with peri‐implantitis commonly show in‐ bone plate. The lowest frequency was noted for isolated buccal
creased PD. In a study evaluating 588 patients with 2,277 implants dehiscence‐type defects (i.e. Class Ia) (5%).58 Similar intraoperative
after a function time of 9 years, PD ≥6 mm was recorded at 59% findings were also reported by Serino et al.57 The majority (66%)
of all implants presenting with moderate/severe peri‐implantitis of the implants investigated (n = 59) exhibited a uniform bone loss
(case definition: BOP+ and bone loss >2 mm).52 Out of the implants at all four aspects. 57 The remaining peri‐implantitis defects mainly
classified as healthy (case definition: BOP‐) or diagnosed with mu‐ featured a more advanced bone loss at the buccal site. These data
cositis (case definition: BOP+ but no bone loss >0.5 mm), 3% and were recently confirmed in a cross‐sectional analysis, also point‐
16% showed PD ≥6 mm, respectively. It was also noted that the ing to an uniform bone loss at all four implant aspects with a high
frequency of implants demonstrating PD ≥6 mm increased with in‐ frequency of Class Ie defects (15/46, 33%).59 Based on the above
creasing severity of peri‐implantitis. studies, it is assumed that peri‐implantitis lesions commonly prog‐
In a cross‐sectional analysis, Schwarz et al. evaluated a total ress circumferentially around the affected implants.
of 238 patients (n = 512 implants) after a median function time Studies reporting on clinical characteristics of implants diag‐ nosed
of 23 months (1 to 80 months). 29 At peri‐implant mucositis sites with peri‐implantitis are summarized in Table 1.
(case definition: BOP+ on at least one aspect of the implant), the
frequency of BOP scores mainly ranged between 33% and 50%,
while the peak was 67% at peri‐implantitis sites (case definition: Periapical peri‐implantitis
BOP+ and/or suppuration and changes in the radiographic bone Apart from peri‐implant infections at sites with deepened probing
level compared to baseline). Diseased implant sites were associ‐ depths, a number of case series also reported on the occurrence of
ated with higher frequencies of 4 to 6 mm PD than implants with a per‐ iapical peri‐implantitis lesions. The affected implants were
healthy peri‐implant mucosa, with an equal distribution between commonly characterized by a periapical radiographic radiolucency with
mucositis and peri‐implantitis sites. PD values of ≥7 mm were only or with‐ out concomitant clinical signs of inflammation, such as
observed at one implant diagnosed with peri‐implantitis. 29 redness, edema, fistula and/ or abscess formation.60‒72 These clinical
and radiographic
 S250

TA B L E 1 Clinical characteristics of peri‐implantitis

Study Type of study Study sample Case definition/inclusion criteria Findings

56
Fransson et al. 2005 Cross‐sectional 82 patients Progressive bone loss Clinical examination
and 200855 5 to 20 years 197 implants identified with progressive bone loss Bone level ≥3 threads & bone loss PD ≥6 mm/Suppuration (% of implants)
mean: 9.4 years 285 implants with no progressive bone loss >0.6 mm No progressive bone loss: 12%/5%
Progressive bone loss: 35%/19%
Schwarz et al. 200758 Cross‐sectional 24 patients Case definition Intraoperative assessment
40 implants diagnosed with PD >6 mm Combination of intrabony and supracrestal
moderate to advanced peri‐implantitis BOP/SUP+ defects; circumferential‐type intrabony
Bone loss defects most frequent (55.3%).
Serino et al. 201357 Cross‐sectional 29 patients Case definition Clinical examination and intraoperative
89 implants diagnosed with PD >4 mm assessment
peri‐implantitis BOP/SUP+ Circumferential‐type bone defects most frequent
Bone loss ≥2 mm (66.0%).
Derks et al. 201652 Cross‐sectional 588 patients Clinical examination
9 years 137 patients diagnosed with mucositis Case definition PD ≥6 mm (% of implants)
62 patients diagnosed with moderate/severe BOP/SUP+ Healthy: 3%
peri‐implantitis Bone loss >2 mm Mucositis: 16%
Moderate/severe peri‐implantitis: 59%
Garcia‐Garcia et al. Cross‐sectional 25 patients Case definition Radiographic and intraoperative assessment
201659 46 implants diagnosed with BOP/SUP+ Circumferential‐type intrabony defects most
peri‐implantitis Bone level >2 mm frequent (32.6%).
Schwarz et al. 201754 Cross‐sectional 60 patients Case definition Clinical assessment with validated ultrasonic
229 implants diagnosed with moderate to BOP/SUP+ A‐sacnner
advanced peri‐implantitis Bone loss Horizontal mucosal thickness (median)
Healthy sites 1.1 mm
Mucositis: 1.7 mm
Peri‐implantitis: 1.61 mm
Schwarz et al. 201729 Cross‐sectional 238 patients Case definition Clinical examination
1 month ‐ 6.7 years 216/512 implants diagnosed with mucositis BOP/SUP+ Higher BOP scores at peri‐implantitis sites when
mean: 2.2 years 46/512 implants diagnosed with peri‐implantitis Changes in the radiographic bone compared to mucositis sites. Similar PD scores.
level compared to baseline (i.e.
prosthesis installation)

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 SCHWARZ et Al . | S251

signs of inflammation were noted between 2 to 8 weeks 68,71 and up to incidence of peri‐implantitis of 31%. Patients suffering from peri‐
4 years65 after implant placement. The majority of the studies reported odontitis at the final examination had significantly higher odds to
a direct correlation between retrograde peri‐implantitis and the exist‐ also have developed peri‐implantitis when compared to individuals
ence of periapical endodontic lesions at adjacent teeth.61‒63,65,67,68,70,72 without periodontitis (OR 9).
A number of cross‐sectional studies reported on prevalence

Oral‐mucosal lesions mimicking peri‐implantitis of peri‐implantitis and analyzed associations with either a his‐
tory of periodontitis or current periodontitis. In a study including
Case reports have described a variety of oral‐mucosal lesions at dental 216 patients were evaluated 9 to 14 years after implant therapy, Roos‐
implants that may mimic peri‐implant diseases. Such lesions include Jansåker et al. reported that implants placed in patients with a
primary malignant tumors (i.e. oral squamous cell carcinoma) 73‒76 or history of periodontits had significantly higher odds (OR 5) for peri‐
metastases77 as well as giant cell and pyogenic granuloma. 78‒86 implantitis when compared to implants in patients without.92,93
While these pathologic conditions share several clinical features Koldsland et al. reported similar findings after examining 109 sub‐
with peri‐implant diseases, they reveal distinct differences to a non‐ jects with 1 to 16 years of follow‐up. 94,95 Thus, patients with a history
specific inflammation at the histopathologic level.86 of periodontitis were found to be at higher risk for peri‐implantitis
(OR 6). Several subsequent studies confirmed this association with
varying degrees of strength.96‒100 Other studies correlated current
Risk factors/indicators for peri‐implantitis
periodontitis with peri‐implantitis, also reporting strong associa‐
Interventional studies of longitudinal design are required to identify tions.52,101,102 In fact, Daubert et al. found that severe periodontitis at
true risk factors for a disease. Observational studies, cross‐sectional follow‐up was the strongest indicator for peri‐implantitis of all
or retrospective in nature, may only describe risk indicators. variables examined, presenting with an unadjusted risk ratio of 7.101
In the following text, potential risk factors/indicators with sub‐ Derks et al., in a 9‐year follow‐up including 588 patients reported an
stantial evidence are addressed in dedicated sections, while fac‐ odds ratio of 4 for patients with current periodontitis. 52
tors with limited evidence are summarized under “Areas of future While the majority of publications is in general agreement when
research”. examining the association between periodontitis and peri‐implan‐
titis, it should also be noted that conflicting reports exist.29,103‒106 Thus,
Marrone et al. examined 103 patients with implant‐supported
History of periodontitis
restorations in function for at least 5 years.103 Neither current peri‐
Periodontitis is a common disease. Its severe form ranks 6th among odontitis nor history of periodontitis were statistically significant
the most prevalent disorders. 87 In a recent survey carried out in the predictors for peri‐implantitis. Also Rokn et al., in a cross‐sectional
United States, Eke et al. reported that roughly 50% of the adult popu‐ study on 134 patients failed to demonstrate a higher risk for peri‐im‐
lation (aged ≥30 years) presented with periodontitis. 88 In individuals plantitis in patients with a history of periodontitis. 104 Disagreement
aged ≥65 years, the corresponding number was 68%. Studies report‐ between studies may be explained by differences in case definitions
ing on the potential association between history of periodontitis for 1) (history of) periodontitis and 2) peri‐implantitis (see Table 2).
(chronic or aggressive) and peri‐implantitis are described in Table 2. Conclusion: There is strong evidence from longitudinal and cross‐
In two 10‐year longitudinal studies, peri‐implantitis was assessed sectional studies that a history of periodontitis constitutes a risk
and correlated with a history of periodontitis. Karoussis et al. pro‐ factor/indicator for peri‐implantitis.
vided implant therapy to 45 patients without a history of periodon‐
titits.89 A total of eight patients were treated with implants after
having successfully completed periodontal therapy. The 10‐year
Smoking
incidence of peri‐implantitis (case definition: PD ≥5 mm, BOP+ and Smoking has been strongly associated with chronic periodontitis, at‐
annual bone loss >0.2 mm) in the non‐periodontitis group was 6% tachment loss as well as tooth loss,107,108 Studies reporting on the
(implant level) compared to 29% in subjects with a history of peri‐ potential association between smoking and peri‐implantitis are de‐
odontitis. Roccuzzo et al. followed 101 patients provided with den‐ scribed in Table 3.
tal implants after having been categorized as 1) periodontally not Lindquist et al. reported that smokers presented with substan‐
compromised, 2) moderately compromised and 3) severely com‐ tially more crestal bone loss than non‐smokers. 109 In line with this
promised.90,91 The authors reported that both the frequency of im‐ observation, several subsequent studies observed a strong asso‐
plant sites demonstrating PD ≥6 mm (2%, 16%, 27%, respectively) ciation between smoking and peri‐implantitis. In a 10‐year cohort
and bone loss ≥3 mm (5%, 11%, 15%, respectively) differed signifi‐ study, Karoussis et al. found that 18% of all implants in smokers de‐
cantly between groups. The results also showed that treatment of veloped peri‐implantitis, while only 6% of implants in non‐smokers
peri‐implantitis was more time consuming in patients with a history were affected.89 Three cross‐sectional studies confirmed these find‐
of periodontitis. In a follow‐up study of 80 patients presenting with ings, reporting odds ratios of 32,110 3,30 and 5,93 respectively.
mucositis at baseline, the incidence of peri‐implantitis over 5 years The majority of publications, however, failed to identify
was assessed by Costa et al.17 The authors observed an overall smoking as a risk factor/indicator for peri‐implantitis. Aguirre‐
Zorzano et al.
 TA B L E 2 History of periodontitis and peri‐implantitis
S252
Study Type of study Study sample History of periodontitis Peri‐implantitis Association

Karoussis Cohort study 53 patients Case definition for periodontitis not Case definition 10‐year incidence of peri‐im‐
|
et al. 8‐12 years 8 patients with history of periodontitis specified. PD ≥5 mm plantitis (implant level)
200389 45 patients with no history of periodontitis Successfully treated prior to implant BOP+ History of periodontitis: 28.6%
therapy. Annual bone loss >0.2 mm No history of periodontitis:
5.8%
Ferreira et al.Cross‐sectional212 patientsCase definition Case definition PD ≥5 mm BOP/SUP+ Odds for peri‐implantitis (patient level
20061020.5‐5 years30 patients with current periodontitis≥4 teeth with PD ≥4 mm and CAL ≥3 mm mean: 3.5 years182 patients with no current periodontitis(at final
Boneexamination)
level (no threshold) Periodontitis: OR 3.1

Roos‐Jansåker et al. Cross‐sectional 9‐ 216 patients Case definition Case definition Odds for peri‐implantitis
14 years Number of patients with/without history % remaining teeth with bone loss ≥4 mm BOP/SUP+ (implant level)
200692,93 mean: 11.0 of periodontitis not reported (prior to implant therapy) Bone loss ≥1.8 mm History of periodontitis: OR 4.7
years Categories: 0‐30% and 31‐100%
Máximo et al. Cross‐sectional 113 patients Case definition Case definition Peri‐implantitis most common
2008100 ≥1 year 33 edentulous patients Number of quadrants showing crestal bone PD ≥5 mm in patients presenting with
mean: 3.4 years 21 patients with no history of periodontal loss BOP/SUP+ periodontal bone loss in all 4
bone loss (at final examination) Bone level ≥3 threads quadrants.
59 patients with history of periodontal
bone loss
Koldsland
Cross‐sectional 103 patients Case definition for current periodontitis Case definition Odds for peri‐implantitis
et al. 201094
1‐16 years 24 patients with history of periodontitis ≥2 teeth with PD ≥5 mm, BOP % bone loss PD ≥4 mm (implant level)
& 201195
mean: 8.4 years (6 patients with current periodontitis) ≥6 mm BOP/SUP+ History of periodontitis: OR 6.2
77 patients with no history of periodontitis (at final examination) Bone loss ≥2 mm
Definition for history of periodontitis
Tooth loss due to periodontitis and bone
loss ≥4 mm at ≥30% of remaining teeth.
101 patientsCase definition for periodontitis
Roccuzzo etnot
al. Cohort study Case definition for peri‐implanti‐ tis not reported. Number of sites with increased PD Association
and bone lossbetween
as well(i)as%patients
of sites treated
with PDfor
≥6 pe
mm
28 patients not periodontally compromisedspecified.
201091 &10 years Based on clinical examination 37 patients moderately
and/or compromisedat
surgery are presented.
baseline. Periodontally compromised 36 patients severely compromisedpatients
(iii) % of patients treated
categorized
for peri‐implantitis
according to
and
n
and depth of periodontal pockets.201290 periodontal status.

Dvorak et al. Cross‐sectional 203 patients Case definition for periodontitis not Case definition No association.
2011106 1‐24 years Number of patients with/without history specified. Patient‐reported. PD >4 mm
mean: 6.0 years of periodontitis not reported BOP/SUP+
Bone loss/level (no threshold)
Costa et al. 80
Cohort
patients
study
with mucositisCase definition Case definition PD ≥5 mm BOP/SUP+ Odds for peri‐implantitis (patient level)
201217 28
5 years
patients with current periodontitis≥4 teeth with PD ≥4 mm and CAL ≥3 mm 52 patients with no current periodontitis(atBone
finallevel
examination)
(no threshold) Periodontitis: OR 9.2 SC
H
W
AR
Z
et
(Continues) Al.
TA B L E 2 (Continued)
SC
H
Study Type of study Study sample History of periodontitis Peri‐implantitis Association
W
Casado et al. Cross‐sectional 215 patients Case definition Case definition Odds for peri‐implantitis AR
Z
201396 1‐8 years 88 with history of periodontitis Bone loss and PD ≥4 mm at ≥30% of BOP+ (patient level) et
mean: 5.6 years 127 with no history of periodontitis remaining sites Annual bone loss >0.2 mm (1 mm History of periodontitis: OR 4.0 Al.

(prior to implant therapy). Patient records. for first year)

Marrone et al. Cross‐sectional 5‐ 103 patients Case definition for current periodontitis Case definition No association.
2013103 18 years 62 patients with history of periodontitis BOP ≥25% & PD ≥5 mm PD >5 mm
mean: 8.5 years (15 patients with current periodontitis) (at final examination). BOP+
41 patients with no history of periodontitis Definition for history of periodontitis not Bone level >2 mm
reported.
Renvert et al. Cross‐sectional 270 patients Case definition for periodontitis not Case definition Odds for peri‐implantitis
201498 mean: 10.1 137 with history of periodontitis specified. Based on patient records, PD ≥4 mm (patient level)
years 133 with no history of periodontitis interview and clinical examination. BOP/SUP+ History of periodontitis: OR 4.5
Bone level >2 mm
Daubert Cross‐sectional
et al. 9‐15 years
96 patients
mean: 10.9 Severe periodontitis defined as the presence of periodontitis with attach‐
Case definition
ment loss
PD≥5
≥4mm
mm BOP/SUP+ Risk for peri‐implantitis (implant level)
2015101years Number of patients with current severe (at
periodontitis
final examination)
not reported Bone loss ≥2 mm Severe periodontitis: RR 7.3

de Araujo Case‐control 1275 patients Tooth loss due to periodontitis. Case definition Odds for peri‐implantitis
Nobre et al. ≥1 year 198/255 cases with history of periodontitis PD ≥5 mm (patient level)
201597 57/1020 controls with history of BOP+ History of periodontitis: OR
periodontitis Bone loss ≥2 mm 19.0
Canullo et al.Cross‐sectional534 patientsCase definition Case definition PD ≥4 mm BOP/SUP+ No association.
2016105mean: 5.1 years140 patients with current periodontitis>30% of remaining teeth with BOP, Bone level >3 mm
394 patients with no current periodontitispresence of PD ≥4 mm and bone loss
(at final examination)

Derks et al. Cross‐sectional 588 patients Case definition Case definition Odds for peri‐implantitis
201652 9 years 140 patients with current periodontitis 352 ≥2 teeth exhibiting BOP/SUP+, attachment BOP/SUP+ (patient level)
patients with not current periodontitis loss ≥2 mm and PD ≥6 mm Bone loss >2 mm Periodontitis: OR 4.1

| S2
53
 S254 | SCHWARZ et Al .

TA B L E 3 Smoking and peri‐implantitis

Study Type of study Study sample Smoking Peri‐implantitis Association

Karoussis et al. Cohort study 53 patients Patient‐reported Case definition Incidence of peri‐im‐
200389 8‐12 years 41 non‐smokers Smoker: smoking at time PD ≥5 mm plantitis (implant
12 smokers of implant installation. BOP+ level)
Annual bone loss >0.2 Non‐smokers: 6.0%
mm Smokers: 17.9%
Roos‐Jansåker 216 patients Patient‐reported Case definition Odds for peri‐implanti‐
et al. 200692,93 Cross‐sectional Number of smokers/ Smoker: smoking at final BOP/SUP+ tis (implant level)
9‐14 years former smokers examination. Bone loss ≥1.8 mm Smoking OR 4.6
mean: 11.0 years not reported.
Máximo et al. Cross‐sectional 113 patients Patient‐reported Case definition No association.
2008100 ≥1 year 60 never‐smokers Smoker: smoking at final PD ≥5 mm
mean: 3.4 years 32 former smokers examination. BOP/SUP+
21 smokers Bone level ≥3 threads
Koldsland et al. 103 patients Patient‐reported No association.
201094 & Cross‐sectional 87 non‐smokers Smoker: smoking at final Case definition
201195 1‐16 years 16 smokers examination. PD ≥4 mm
mean: 8.4 years BOP/SUP+
Bone loss ≥2 mm
Rinke et al. Cross‐sectional 89 patients Patient‐reported Case definition Odds for peri‐implanti‐
2011110 2‐11 years 72 non‐smokers Smoker: smoking at final PD ≥4 mm tis (patient level)
mean: 5.7 years 17 smokers examination and BOP+ Smoker: OR 31.6
former smokers Bone loss ≥3.5 mm
(cessation <5 years).
Dvorak et al. Cross‐sectional 1‐24 years
203 patientsPatient‐reported Number of smokersSmoker: smoking
Case definition
at final PD >4 mm BOP/SUP+ No association.
2011106 mean: 6.0 years not reported.examination. Bone loss/level (no
threshold)

Casado et al. Cross‐sectional 215 patients Patient‐reported Case definition No association.

201396 1‐8 years 194 non‐smokers Smoker: smoking at final BOP+
mean: 5.6 21 smokers examination. Annual bone loss >0.2
years mm (1 mm for first
year)
Marrone et al. 103 patients Patient‐reported No association.
2013103 Cross‐sectional 83 non‐smokers Smoker: smoking at final Case definition
5‐18 years 20 smokers examination. PD >5 mm
mean: 8.5 years BOP+
Bone level >2 mm
Renvert et al. Not reported 270 patients Patient‐reported Case definition Signficant association
201498 155 non‐smokers Smoker: smoking at final PD ≥4 mm in unadjusted but not

110 smokers examination and BOP/SUP+ in adjusted analysis.

former smokers Bone level >2 mm
(cessation ≤10 years).
Aguirre‐Cross‐sectional239 patients Zorzano et al.6 months ‐ 17 years164 non‐smokers
Patient‐reported Smoker: smoking at final
Case definition BOP+ No association.
2015111mean: 5.3 years75 smokers examination. Bone loss >1.5 mm

Daubert et al. Cross‐sectional 96 patients Patient‐reported at time Case definition No association

2015101 9‐15 years 89 non‐smokers of implant installation PD ≥4 mm between peri‐implan‐
mean: 10.9 years 7 smokers and final examination. BOP/SUP+ titis and (i) smoking
Smoker: smoking at Bone loss ≥2 mm status at initial/final
initial/final examation, (ii) pack/
examination. years.
Calculation of pack/years.
de Araujo Case‐control 1275 patients Patient‐reported Case definition No association.
Nobre et al. ≥1 year 95/255 cases are Smoker: smoking at final PD ≥5 mm
201597 smokers examination. BOP+
242/1020 controls Bone loss ≥2 mm
are smokers
(Continues)
 SCHWARZ et Al . | S255

TA B L E 3 (Continued)

Study Type of study Study sample Smoking Peri‐implantitis Association

Canullo et al. Cross‐sectional 534 patients Patient‐reported Case definition No association.

2016105 mean: 5.1 years 393 non‐smokers Smoker: smoking at final PD ≥4 mm
141 smokers examination. BOP/SUP+
Bone level >3 mm
Derks et al. Cross‐sectional 588 patients Patient‐reportedCase definition Smoker: smoking at timeBOP/SUP+
Signficant association in unadjusted but not
201652 9 years 467 non‐smokersof implant installation.Bone loss >2 mm in adjusted analysis.
121 smokers

Rokn et al. Cross‐sectional 134 patients Patient‐reported Case definition No association.

2017104 1‐11 years 126 non‐smokers Smoker: smoking at final BOP/SUP+
mean: 4.4 years 8 smokers examination. Bone level >2 mm
Dalago et al. Cross‐sectional 183 patients Patient‐reported Smoker: smoking
Caseatdefinition
final PD >5 mm BOP/SUP+ No association.
201799 1‐14 years 162 non‐smokers examination. Bone level >2 mm
21 smokers

Schwarz et al. Cross‐sectional 238 patients Patient‐reported Case definition Odds for peri‐implanti‐
201729 1 month ‐ 6.7 years 204 non‐smokers Smoker: smoking at time BOP/SUP+ tis (patient level)
mean: 2.2 years 34 smokers of implant installation. Changes in the Smoking: OR 2.7
radiographic bone
level compared to
baseline (i.e.
prosthesis
installation)

examined 239 implant‐carrying individuals after a mean follow‐up

periodontitis.115,116 Table 4 summarizes studies on its potential as‐
time of about 5 years and found an overall prevalence of peri‐implan‐
sociation with peri‐implantitis.
titis of 15%.111 Smokers were not at higher risk. Results from other
A number of authors have indicated that patients with diabetes
cross‐sectional studies confirmed their findings. 95,96,99‒101,103‒106 It should
are at higher risk for peri‐implantitis. Thus, Ferreira et al. recorded
be observed that three different studies reported on an as‐ sociation
peri‐implantitis in 24% of individuals who either medicated for gly‐
between smoking and peri‐implantitis in their respective initial
caemic control or presented with fasting blood sugar ≥126 mg/dL
univariate analyses.52,97,98 However, in the following calcula‐ tions with
at the final examination 102 In contrast, only 7% of non‐diabetic pa‐
adjustments for confounding and interaction (multivari‐ ate
tients were diagnosed accordingly. The authors reported an OR of
analyses), smoking was not retained as a relevant predictor for peri‐
1.9. Recent findings from a study involving 96 patients with 225 im‐
implantitis. This indicates that smoking may be confounded by other
plants demonstrated, after a mean follow‐up of 11 years, a 3‐fold
background variables, e.g. history of periodontitis. The rea‐ sons for
risk (Risk ratio 3, implant level) for peri‐implantitis in subjects who
the conflicting findings and the apparent weak association between
were diagnosed with diabetes at time of implant placement. 101 This
smoking and peri‐implantits are currently not understood but may be
analysis, however, was not adjusted for potential confounding. Tawil
related to differences in categorization of smokers and non‐smokers.
et al. followed 45 patients with diabetes for a mean of 42 months
Thus, criteria for the factor “smoking" varied consid‐ erably from study
(range 1 to 12 years).117 In subjects with a mean HbA1c level ≤7%, no
to study. Furthermore, all of the identfied studies relied solely on
implants were diagnosed with peri‐implantitis. In patients with
patient‐reported information for the assessment of smoking status.
elevated HbA1c levels (7% to 9%), six out of 141 implants developed
Conclusion: There is currently no conclusive evidence that smok‐
peri‐implantitis.
ing constitutes a risk factor/indicator for peri‐implantitis.
A number of studies failed to identify diabetes as a risk for peri‐
implantitis. In the retrospective study by Costa et al., patients with
Diabetes diabetes diagnosed with mucositis were not at higher risk to develop
peri‐implantitis when compared to non‐diabetics.17 Similarly, a lack
Diabetes mellitus comprises a group of metabolic diseases where
of assocation between peri‐implantitis and diabetes was reported in
type 1 describes an autoimmune destruction of insulin‐producing β‐
the majority of available cross‐sectional studies.52,93,98‒100,103,104,106 It
cells and type 2 is characterized by insulin resistance. 112 The global
should be pointed out that the assessment of diabetes in all but three
prevalence of diabetes in the adult population is estimated at around
studies17,102,117 was solely based on patient‐reported informa‐ tion. In
8%,113,114 and the disorder has been identified as a risk factor for
two of the three reports an association was found between
diabetes102 or HbA1c levels117 and peri‐implantitis.
TA B L E 4 Diabetes and peri‐implantitis S256

Study Type of study Study sample Diabetes Peri‐implantitis Association |

102
Ferreira et al. 2006 Cross‐sectional 212 patients Fasting blood sugar ≥126 mg/dl or Case definition Peri‐implantitis (patient
0.5‐5 years 183 non‐diabetic patients intake of anti‐diabetic medicine PD ≥5 mm level)
mean: 3.5 years 29 patients with diabetes (at final examination) BOP/SUP+ Diabetes: OR 1.9
Bone level (no threshold)
Roos‐Jansåker et al. Cross‐sectional 216 patients Patient‐reported Case definition No association.
200692,93 9‐14 years Number of patients with/without (at final examination) BOP/SUP+
mean: 11.0 years diabetes not reported. Diabetes considered in factor Bone loss ≥1.8 mm
“General disease"
Máximo et al. 2008100 Cross‐sectional 113 patients Patient‐reported Case definition No association.
≥1 year 111 non‐diabetic patients (at final examination) PD ≥5 mm
mean: 3.4 years 2 patients with diabetes BOP/SUP+
Bone level ≥3 threads
Tawil et al. 2008117 Cohort study 45 patients with diabetes Regular assessments of Case definition for peri‐implantitis Peri‐implantitis (implant
1‐12 years 22 patients with HbA1c level ≤7% HbA1c levels during pre‐ and not reported. level)
mean: 3.5 years 22 patients with HbA1c level 7% postoperative period. HbA1c level ≤7%: 0%
to 9% HbA1c level 7% ‐ 9%:
1 patient with HbA1c level >9% 4.3%
HbA1c level >9%: 9.1%
Dvorak et al. 2011106 Cross‐sectional 203 patients Patient‐reported Case definition No association.
1‐24 years Number of patients with/without (at final examination) PD >4 mm
mean: 6.0 years diabetes not reported. BOP/SUP+
Bone loss/level (no threshold)
Costa et al. 201217 Cohort study 80 patients with mucositis Fasting blood sugar ≥126 mg/dL or Case definition No association.
5 years 69 non‐diabetic patients intake of anti‐diabetic medicine PD ≥5 mm
11 patients with diabetes (at final examination) BOP/SUP+
Bone level (no threshold)
Marrone et al. 2013103 Cross‐sectional 103 patients Patient‐reported Case definition No association.
5 to 18 years 96 non‐diabetic patients (at final examination) PD >5 mm
mean: 8.5 years 7 patients with diabetes BOP+
Bone level >2 mm
Renvert et al. 201498 Not reported 270 patients Patient‐reported Case definition Association in unadjusted
259 non‐diabetic patients (at final examination) PD ≥4 mm (OR 6.1, P = 0.09) but
11 patients with diabetes BOP/SUP+ not in adjusted analysis.
Bone level >2 mm
Daubert et al. 2015101 Cross‐sectional 96 patients Patient records/Patient‐reported Case definition Risk for peri‐implantitis
9 to 15 years 91 non‐diabetic patients (prior to implant therapy) PD ≥4 mm (implant level)
mean: 10.9 years 5 patients with diabetes BOP/SUP+ Diabetic at baseline: RR
Bone loss ≥2 mm 3.0 (unadjusted SC
analysis) H
W
AR
(Continues) Z
et
Al.
SCHWARZ et Al . | S257

Conclusion: Available evidence is inconclusive as to whether dia‐

betes is a risk factor/indicator for peri‐implantitis.

Poor plaque control/lack of

No association.

No association.
No association. Association
regular maintenance therapy
As demonstrated in classical studies on periodontal diseases, lack of
regular maintenance therapy is associated with tooth mortality and
clinical attachment loss at teeth. 26,118‒121 These findings have high‐
lighted the importance of self‐performed and professionally‐admin‐
istered infection control measures in the prevention of periodontal
diseases. Studies on the potential association between poor plaque
control or lack of regular maintenance therapy and peri‐implantitis
Peri‐implantitis

are presented in Table 5.

Results from one longitudinal study including patients diag‐
nosed with mucositis indicated the importance of plaque control
in the prevention of peri‐implantitis. 17 The analysis showed that the
incidence of peri‐implantitis over a 5‐year period was lower in
patients attending maintenance therapy (18%) when compared to
Patient records/Patient‐reported (prior to implant therapy)
Patient records/Patient‐reported
(prior to implant therapy) Diabetes

individuals without supportive care (44%). These findings are in

aggreement with Roccuzzo et al.90 The authors reported that
patients who, during a 10‐year period, failed to adhere to the
recommended maintenance therapy required substantially more
treatment for peri‐implantitis (41%) than those attending the fol‐
low‐up visits (27%). Results from a cross‐sectional study are also in
agreement. Patients complying to maintenance therapy following
implant therapy during a mean obersvation time of 3.8 years were
less likely to be diagnosed with peri‐implantitis than non‐compliers
Patient records/Patient‐reported

(OR 0.14).122
Cross‐sectional reports assessing self‐performed plaque control
and its association with peri‐implantitis demonstrated a strong
Study sample

correla‐ tion. In four studies, poor plaque control at the final

examination was the strongest statistical predictor for peri‐
implantitis with ORs ranging from 5 to 14.29,102,104,111 A more modest
assocation (ORs 3 to 4) was described by one additional cross‐
588 patients

sectional105 and one case‐control study.97

Contradictory data have also been reported. A total of four
pub‐ lications were identified that failed to observe correlations
between cross‐sectional assessments of plaque scores and peri‐
implanti‐ tis.93,95,103,106 In this context, it should be considered that a
Rokn et al. 2017104 Cross‐sectional 1 to 11 years
Type of study

one‐time assessment of plaque may not necessarily reflect the

long‐term level of self‐performed plaque control.
Other factors related to oral hygiene measures at implants may
also be considered. Recently, Souza et al. reported that brushing at
implant sites with keratinized mucosa (KM) <2 mm was associated
with considerably more discomfort when compared to brushing at
TA B L E 4 (Continued)

sites with KM ≥2 mm.123 The authors also noted higher scores for
plaque and bleeding at sites with reduced KM. Serino and Ström
Dalago et al. 201799
Derks et al. 201652 Study

evaluated the accessibility of implant‐supported restorations for

oral hygiene measures in patients diagnosed with peri‐implanti‐ tis.124
The authors noted that only few sites with access for oral hygiene
were affected (18%), while 65% of the non‐cleansable sites showed
peri‐implantitis.
 S258
TA B L E 5 Poor plaque control/lack of regular maintenance therapy and peri‐implantitis |
Plaque control/maintenance
Study Type of study Study sample therapy Peri‐implantitis Association

Ferreira et al. 2006102 Cross‐sectional 212 patients Plaque score Case definition Odds for peri‐implantitis
0.5 to 5 years 43 patients with good plaque (at final examination) PD ≥5 mm (patient level)
mean: 3.5 control BOP/SUP+ Poor plaque control: OR
years 123 patients with poor plaque Bone level (no threshold) 3.8
control Very poor plaque control:
46 patients with very poor plaque OR 14.3
control

Roos‐Jansåker et al. Cross‐sectional 216 patients Presence of plaque at implant level Case definition No association.
200692,93 9 to 14 years Number of patients with/without (at final examination) BOP/SUP+
mean: 11.0 years good plaque control not Bone loss ≥1.8 mm
reported.
Koldsland et al. 201094 Cross‐sectional 103 patients Plaque score and presence of Case definition No association.
& 201195 1 to 16 years 10 patients with plaque score ≥30% plaque at implant level PD ≥4 mm
mean: 8.4 years 93 patients with plaque score <30% (at final examination) BOP/SUP+
Recall visits Bone loss ≥2 mm
Patient‐reported
Rinke et al. 2011110 Cross‐sectional 89 patients Maintenance therapy Case definition Odds for peri‐implantitis
2 to 11 years 58 patients attending recommended PD ≥4 mm (patient level)
mean: 5.7 years maintenance visits BOP+ Regular maintenance
31 patients not attending recom‐ Bone loss ≥3.5 mm therapy: OR 0.09
mended maintenance visits
Dvorak et al. 2011106 Cross‐sectional 177 patients Presence of plaque at implant level Case definition No association.
1 to 24 years Number of patients with/without (at final examination) PD >4 mm
mean: 6.0 years good plaque control not BOP/SUP+
reported. Bone loss/level (no threshold)
Costa et al. 201217 Cohort study 80 patients with mucositis Maintenance therapy Case definition Odds for peri‐implantitis
5 years 39 patients with maintenance Patient‐reported and patient PD ≥5 mm (patient level)
therapy records BOP/SUP+ No maintenance therapy:
41 patients without maintenance Plaque index Bone level (no threshold) OR 1.8
therapy (at final examination)
Roccuzzo et al. 201091 Cohort study 101 patients Maintenance therapy Case definiton for peri‐implantitis Treatment for peri‐implan‐
and 201290
10 years 79 patients adhering to mainte‐ not reported. titis (patient level)
nance therapy Treatment for peri‐implantitis Adherence to mainte‐
22 patients not adhering to (surgery and/or systemic nance therapy: 27%
maintenance therapy antibiotics). Non‐adherence to
maintenance therapy: SC
41% H
W
AR
Z
(Continues) et
Al.
TA B L E 5 (Continued) SC
H
Plaque control/maintenance W
AR
Study Type of study Study sample therapy Peri‐implantitis Association
Z
103 et
Marrone et al. 2013 Cross‐sectional 103 patients Plaque index Case definition No association. Al.
5 to 18 years 16 patients with plaque score ≥30% (at final examination) PD >5 mm
mean: 8.5 years 87 patients with plaque score <30% BOP+
Bone level >2 mm
Aguirre‐Zorzano et al. Cross‐sectional 239 patients Plaque index Case definition Odds for peri‐implantitis
2015111 6 months to 17 years 50 patients with plaque score ≥25% (at final examination) BOP+ (implant level)
mean: 5.3 years 189 patients with plaque score Bone loss >1.5 mm Plaque ≥25%: OR 5.4
<25%
de Araujo Nobre et al. Case‐control 1275 patients Presence of plaque at patient level Case definition Odds for peri‐implantitis
201597 ≥1 year Plaque present in 108/255 cases (at final examination) PD ≥5 mm (patient level)
Plaque present in 67/1020 controls BOP+ Plaque: OR 3.6
Bone loss ≥2 mm
Canullo et al. 2016105 Cross‐sectional 534 patients Plaque index Case definition Odds for peri‐implantitis
mean: 5.1 years Number of patients with/without (at final examination) PD ≥4 mm (patient level)
good plaque control not BOP/SUP+ Plaque >30%: OR 3.4
reported. Bone level >3 mm
Derks et al. 201652 Cross‐sectional 588 patients Recall visits Case definition No association.
9 years 474 patients attending annual Patient records BOP/SUP+
maintenance visits Bone loss >2 mm
101 patients not attending annual
maintenance visits
Rokn et al. 2017104 Cross‐sectional 134 patients Plaque index Case definition Odds for peri‐implantitis
1 to 11 years Number of patients with/without (at final examination) BOP/SUP+ (implant level)
mean: 4.4 years good plaque control not Bone level >2 mm Plaque index (categoriza‐
reported. tion not reported): OR
5.4
Schwarz et al. 201729 Cross‐sectional 238 patients Plaque index Case definition Odds for peri‐implantitis
1 month to 6.7 years Number of patients with/without (at final examination) BOP/SUP+ (patient level)
mean: 2.2 years good plaque control not Changes in the radiographic bone Plaque ≥33%: OR 9.3
reported. level compared to baseline (i.e.
prosthesis installation)
Monje et al. 2017122 Cross‐sectional 115 patients Plaque index Case definition Prevalence of
3 to 4.5 years mean: 3.8 Patients categorized according to (at final examination) BOP/SUP+ peri‐implantitis:

years frequency of maintenance visits Recall visits Changes in the radiographic bone Regular compliers: 72.7%
Patient records on early marginal level (≥2 mm) compared to were healthy, 4.5% had
bone loss baseline (i.e. prosthesis peri‐implantitis.
installation) Non‐compliers: 53.5%
Alternative case definitions were were healthy, and
further explored (i.e. ≥3 mm and 23.9% had peri‐implan‐ | S2
≥4 mm with signs of titis (OR=0.14)
59
inflammation)
 S260 | SCHWARZ et Al .

Conclusion: There is evidence that poor plaque control and lack However, the proportions of diseased implant sites showing show‐
of regular maintenance therapy constitute risk factors/indicators for ing excess cement varied considerably among studies and ranged
peri‐implantitis. between 9% and 81%. Accordingly, several implant sites show‐
ing excess cement exhibited no disease.132‒136 Furthermore, ce‐ ment‐

Areas of future retained restorations were not found to be at higher risk for peri‐
implantitis when compared to screw‐retained reconstruc‐

research Keratinized tions.52,101,103,137 Nevertheless, a systematic review emphasized that

the rough surface structure of cement remnants may facilitate
retention and biofilm formation.138
mucosa
Conclusion: It is suggested that excess cement is a potential risk
The evidence that there is a need of a keratinized mucosa (KM) to factor/indicator for peri‐implantitis.
maintain peri‐implant health is still limited. 125,126 Previous systematic
reviews have indicated that a KM of <2 mm was associated with more
plaque accumulation and peri‐implant soft tissue inflammation when
Genetic factors
126,127
compared with implants that were surrounded by a KM of ≥2 mm. Gene polymorphisms may affect gene expression, protein production
In particular, a meta‐ analysis pointed to statistically significant differ‐ and cytokine secretion.139 Several observational studies have
ences in terms of plaque scores, modified gingival index, mucosal addressed the potential association between various gene
reces‐ sion and attachment loss in favour of sites with a wider KM.127 polymorphisms and the occurence of peri‐implantitis, with the
These findings were also supported by recent observational majority focussing on IL‐1.140‒144 Based on a cross‐sectional analysis,
studies.105,123,128‒130 In a cross‐sectional analysis, Ladwein et al. evaluated Gruica et al. reported that 64 out of 180 patients revealed a positive IL‐
211 patients (n = 967 implants) after a mean observation period of 8 1 composite gene polymorphism (IL‐1α +4845; IL‐1β +3954) and a total
years.130 Implant sites lacking KM were associated with significantly of 34 patients (51 implants) were associated with biological
higher plaque scores, marginal bleeding and BOP scores than sites with complications (unclear case definition) at 8 to 15 years after implant
KM. However, no significant differences were noted with regard to PD therapy.141 An association between a posi‐ tive IL‐1 composite gene
and radiographic bone levels. polymorphism and the occurrence of biologi‐ cal complications was,
Another cross‐sectional analysis of 36 patients (n = 110 implants) however, observed only in a subgroup of heavy smokers (≥20 cigarettes
after an observation period of at least 6 months also pointed to sig‐ per day). In another cross‐sectional analysis, Laine et al. identified a
nificantly more plaque, marginal bleeding and mucosal inflamma‐ significantly higher prevalence of IL‐1 receptor antagonist (IL‐1RA)
tion as well as greater mucosal recession at sites where KM was ≤2 polymorphisms in patients that were diagnosed with peri‐implantitis
mm.129 Souza et al. observed that implant sites with a KM of <2 mm (case definition: BOP+ and/or suppuration, bone loss >3 threads at
had significantly higher plaque and BOP scores and were associated machined implants) when compared with patients showing healthy
with an increased brushing discomfort than implant sites with a KM control implants (57% vs. 33%; OR 3).140 Similar find‐ ings were
123
of ≥2 mm. This finding was also supported by data from another reported by Hamdy and Ebrahem, showing that a positive IL‐1
cross‐sectional analysis (n = 60 patients) indicating that implants with composite gene polymorphism (IL‐1α ‐889; IL‐1β +3954) was sig‐
a KM of <2 mm revealed a significantly higher levels of plaque accu‐ nificantly higher among patients suffering from peri‐implantitis. 143
mulation as well as increased BOP+ and PD values when compared However, this association was not confirmed in other cross‐sectional
with implant sites with a KM of ≥2 mm. 128 Canullo et al. reported analyses.142,144,145 Recent observational studies have also pointed to
that periodontally healthy patients diagnosed with peri‐implantitis a potential association with gene polymorphisms of osteoprote‐
(53 out of 534 patients) had higher plaque and BOP scores as well as gerin,146,147 IL‐6,148 CD14‐159 C/T and TNFα ‐308 A/G.149
higher percentages of implants with a KM of <2 mm. 105 Recently, in a Conclusion: While prospective clinical studies and studies with
cross‐sectional analysis at 10 years after implant placement, Rocuzzo sufficient sample size are still lacking, the available evidence points
et al. reported that, even in patients with a sufficient oral hygiene, to a potential influence of various gene polymorphisms in the patho‐
the absence of KM was associated with higher plaque scores.131 genesis of peri‐implantitis.
Conclusion: While studies suggest that the absence or a reduced
width of KM may negatively affect self‐performed oral hygiene mea‐
sures, there is limited evidence that this factor constitutes a risk for Systemic conditions
peri‐implantitis. The association of systemic conditions (other than diabetes) with peri‐
implantitis has rarely been studied and is therefore unclear. A cross‐

Excess cement sectional study reported a higher risk for peri‐implantitis in patients
diagnosed with cardiovascular disease (OR 9) and rheu‐ matoid
Several observational studies have reported on a correlation be‐ arthritis (OR 7).98 Koldsland et al. evaluated cardiovascular disease but
tween excess cement and the prevalence of peri‐implant diseases. failed to observe an association with peri‐implantitis. 95 Roos‐Jansåker
Employing a variety of different case definitions, it was suggested et al.,93 Casado et al.,96 and Canullo et al.105 com‐ bined different
that the presence of excess cement was closely linked to the oc‐ systemic diseases into one parameter and found no
currence of either peri‐implant mucositis or peri‐implantitis.132‒136
 SCHWARZ et Al . | S261

elevated risk for peri‐implantitis in their respective analyses. Other implants with mucositis and experimental peri‐implantitis were ex‐
studies considered osteoporosis, 100,106 osteopenia,100,106 thyroid posed to lateral static load by means of expansion screws. 153 There
disease,99,106 hepatitis,99,103 BMI100 as well as radiation and chemo‐ was no difference in terms of bone level changes between loaded and
therapy.97 No association with peri‐implantitis was observed. It may be unloaded implants. Lateral load did not induce bone loss at mucositis
questioned whether existing studies evaluating risk factors/indi‐ cators sites. These findings were supported by Heitz‐Mayfield et al., 154 since in
for peri‐implantitis are adequately powered to detect associa‐ tions their study occlusal overload at implant sites with plaque control in the
with rare disorders. dog did not result in increased PD or BOP scores over unloaded (i.e. no
Conclusion: Evidence suggesting systemic conditions (other than crowns) control implants at 8 months.
diabetes) to be a risk factor/indicator for peri‐implantitis is limited. Cross‐sectional analysis revealed that clinical signs of occlusal
overload (e.g. abutment fracture, loss of retention, chipping, dynamic

Iatrogenic factors occlusal measurements) were identified at three out of 207 implants
with healthy peri‐implant conditions, whereas the ratio changed to
The Consenus report of the 7th European Workshop on 27/125 at peri‐implantitis sites (OR 19). 150 It should be noted that only
Periodontology recognized that the onset and progression of peri‐ patients diagnosed with peri‐implantitis were considered in the
implantitis may be influenced by iatrogenic factors such as “inade‐ analysis. In a population of 183 patients with a total of 916 implants,
quate restoration‐abutment seating, overcontouring of restorations Dalago et al.99 identified that wear facets on the implant supported
1
or implant‐malpositioning”. It appears reasonable that the implant crowns were associated with peri‐implantitis (OR 2).
position and design of the suprastructure should facilitate access Conclusion: There is currently no evidence that occlusal over‐
for self‐performed oral hygiene and professionally administered load constitutes a risk factor/indicator for the onset or progression
plaque removal. 3 However, studies examining the role of iatrogenic of peri‐implantitis.
factors in the development of peri‐implant diseases are still scarce.
In a restrospective analysis, it was suggested that peri‐implanti‐
tis was linked with malpositioning (OR 48) and bone augmentation
Titanium particles
(OR 2).150 The potential association between bone augmentation In an analysis of archive material of human biopsies, it was reported
procedures and peri‐implantitis was also addressed in two cross‐ that the inflammatory cell infiltrate at peri‐implantitis sites occasion‐
sectional studies. 105,151 Canullo et al. reported that in patients (n ally (i.e. seven out of 36 biopsies) revealed residues of particles fea‐
= 53) diagnosed with peri‐implantitis (case definition: BOP+ and/or turing titanium peaks in the energy dispersive x‐ray spectroscope.32
suppuration, PD ≥4 mm, radiographic bone level >3 mm), 18% of the Similar findings were also reported by Fretwurst et al., 155 since metal
diseased implants had received a bone grafting procedure at instal‐ particles (i.e. titanium and iron) were identified in nine out of 12
lation while the percentage of healthy implants sites with a history of human hard and soft tissue biopsies taken at peri‐implantitis sites.
bone augmentation was significantly smaller (7%). 105 Both studies, however, were lacking tissue biopsies retrieved from
In another cross‐sectional study, Schwarz et al. evaluated the clinically healthy implant sites (e.g. taken during the removal of mal‐
im‐ pact of the outcome of guided bone regeneration in positioned or fractured implants).
dehiscence‐type bone defects on peri‐implant health. 151 The In a cytological analysis of oral smears taken from the peri‐im‐
residual defect height was assessed 4 months following grafting. plant mucosa of 30 patients, Olmedo et al. identified metal‐like
After 4 years of follow‐ up, it was observed that implants with particles at both healthy and diseased (i.e. peri‐implantitis) implant
residual defects of >1 mm were at a higher risk of developing peri‐ sites.156 However, the titanium concentration appeared to be higher
implant disease. in patients suffering from peri‐implantitis.
Conclusion: In the absence of sufficient data, it appears reason‐ Conclusion: At the time being, the available evidence does not
able to suggest that implant position and design of the suprastruc‐ allow for an evaluation of the role of titanium or metal particles in
ture may influence the access for home care‐ and professionally the pathogenesis of peri‐implant diseases.
administered plaque removal. A number of additional factors have been associated with peri‐
implantitis in case reports, finite‐element analyses or pre‐clinical

Occlusal overload research (e.g. bone compression necrosis, 157,158 over‐heating,159 mi‐
cromotion,160 and biocorrosion 161). The importance of such factors
In the presence of plaque, the potential influence of excessive occlusal should be evaluated in future research.
overload152 and lateral static load153 on peri‐implantitis has been ad‐
dressed in animal studies. In particular, employing the ligature model
in dogs, Kozlovsky et al. subjected titanium abutments connected to Does progressive crestal bone loss around implants
machined implants to either a supra‐ (i.e. overload), or infra‐occlusion
occur in the absence of soft tissue inflammation?
(i.e. unloaded) over a period of 12 weeks. 152 At control sites (i.e. im‐ It is important to distinguish between initial physiological bone re‐
plants with plaque control), overload was associated with an improved modeling and progressive crestal peri‐implant bone loss, with the
osseointegration over unloaded implants. No data on changes of cr‐ latter implying that a pathological process is ongoing. The initial
estal bone levels were presented. In the study by Gotfredsen et al.,
 S262 | SCHWARZ et Al .

remodeling of the crestal bone is considered to be a physiological pro‐ periodontitis, poor plaque control skills and no regular mainte‐
cess following implant placement. 1 This process is influenced by a va‐ nance care after implant therapy. Data identifying “smoking" and
riety of biological (e.g. mucosal thickness 162), technical (e.g. prosthetic “diabetes" as potential risk factors/indicators for peri‐implantitis
connections163) and surgical (e.g. implant positioning 164,165) factors. are inconclusive.
Observational studies have indicated that crestal bone level 5b) There is some limited evidence linking peri‐implantitis to other fac‐
changes at implants are commonly associated with clinical signs of tors such as: post‐restorative presence of submucosal cement, lack
inflammation. In a retrospective analysis, Fransson et al. evaluated of peri‐implant keratinized mucosa and positioning of implants
the prevalence of subjects with progressive bone loss (bone level >3 that make it difficult to perform oral hygiene and maintenance.
threads and bone loss ≥0.6 mm with year 1 as baseline) at machined/ 6) Evidence suggests that progressive crestal bone loss around im‐
turned implants.56 Between 5 and 23 years after loading, the preva‐ plants in the absence of clinical signs of soft tissue inflammation is
lence of progressive bone loss amounted to 28% at the subject‐ and a rare event.
12% at the implant level. In an analysis of a subgroup of these patients,
clinical signs of inflammation (i.e. BOP+, suppuration, PD >6 mm) were
more frequent at sites demonstrating “progressive bone loss”.55 In par‐
ticular, the percentages of BOP+, suppuration and PD ≥6 mm at ACKNOWLEDGMENTS AND DISCLOSURES

implant sites without progressive bone loss were 91%, 5%, and 12% This narrative review was self‐funded by the authors and their institu‐
compared to 94%, 19%, and 35% at implant sites with progressive tions. Frank Schwarz has received research grants and lecture fees
bone loss. from the Oral Reconstruction Foundation (Basel, Switzerland), Electro
In another cross‐sectional analysis including 427 patients, Derks Medical Systems (Nyon, Switzerland), Geistlich Pharma (Wolhusen,
et al. observed that, over a 9‐year period, bone loss (>0.5 mm) had Switzerland), Institute Straumann (Basel, Switzerland) and ITI (Basel,
occurred at 629 (40%) out of 1,578 implants. 52 Of these 629 im‐ Switzerland). Alberto Monje has received a scholarship from ITI,
plants, 393 (63%) also presented with soft tissue inflammation education/research grants from Osteology Foundation (Luzerne,
(BOP+) at the final examination. At implants presenting with more Switzerland), ITI and Mozo Grau (Valladolid, Spain) and lecture fees
pronounced bone loss (>1, >2, >3, >4 mm), BOP+ was recorded at from Institute Straumann and ITI. Jan Derks has received lecture fees
72%, 80%, 87%, and 88%, respectively. from DENTSPLY Implants (Mölndal, Sweden) and ITI. Hom‐Lay Wang
Similarly, a prospective analysis of implants with a modified receives research grants from BioHorizons (Birmingham, Alabama)
surface over a period of 10 years indicated, that crestal bone level and Osteogenics Biomedical (Lubbock, Texas) for conducting research
changes (>0.5; >1.0; >2.0 mm) were commonly associated with clini‐ at the University of Michigan, Ann Arbor, Michigan, as well as lecture
cal signs of inflammation (BOP+).166,167 honoraria from BioHorizons, Neobiotech (Seoul, South Korea), Botiss
Conclusion: Evidence suggests that progressive crestal bone loss Biomaterials (Zossen, Germany), TRI Dental Implants (Hünenberg,
around implants in the absence of clinical signs of soft tissue inflam‐ Switzerland), Osteogenics Biomedical, and Institute Straumann.
mation is a rare event.

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