Received: 15 February 2024 Revised: 19 March 2024 Accepted: 28 March 2024

DOI: 10.1111/cid.13330

SYSTEMATIC REVIEW

History of periodontitis as a risk factor for implant failure

and incidence of peri-implantitis: A systematic review,
meta-analysis, and trial sequential analysis of prospective
cohort studies

Matteo Serroni 1,2 | Wenche S. Borgnakke 2,3 | Luigi Romano 1 |

Giuseppe Balice 1 | Michele Paolantonio 1 | Muhammad H. A. Saleh 3 |
2
Andrea Ravidà

1
Unit of Periodontics and Dental Hygiene,
Department of Innovative Technologies in Abstract
Medicine & Dentistry, University ‘G.
Introduction: Dental implants are widely employed as dependable replacements for
D'Annunzio’ of Chieti-Pescara, Chieti, Italy
2
Department of Periodontics and Preventive
lost teeth. However, it is crucial to establish, solely through prospective cohort stud-
Dentistry, University of Pittsburgh School of ies, whether a history of periodontitis indeed constitutes a significant risk factor for
Dental Medicine, Pittsburgh,
Pennsylvania, USA
implant failure.
3
Department of Periodontics and Oral Methods: A systematic literature search was conducted in October 2022 in several
Medicine, University of Michigan School of electronic databases with subsequent manual updates. Only original prospective
Dentistry, Ann Arbor, Michigan, USA
cohort studies evaluating the implant (loss) rate ≥1 year after implant loading were
Correspondence
included. Logarithmic risk ratio and weighted mean differences were calculated.
Matteo Serroni, Department of Innovative
Technologies in Medicine & Dentistry, Study results were summarized using random effects meta-analyses evaluated by
University ‘G. D'Annunzio’ of Chieti, Via dei
trial sequential analyses. The Newcastle-Ottawa scale evaluated study bias and the
Vestini 31, 66100 Chieti Scalo, Chieti, Italy.
Email: serronimatteo@gmail.com GRADE approach assessed the certainty/quality of the evidence.
Andrea Ravidà, Department of Periodontics Results: A total of 14 publications reporting on 12 prospective cohort studies were
and Preventive Dentistry, University of
included. Low evidence certainty/quality evidence due to the absence of randomized
Pittsburgh School of Dental Medicine 3501
Terrace Street, Pittsburgh, Pennsylvania, clinical trials revealed significantly greater odds of failure in patients with a history of
15213, USA.
periodontitis at follow-ups both after ≤5 years (OR = 1.65; 95% CI: 1.12–2.44;
Email: andrearavida@pitt.edu
p = 0.012) and >5 years (OR = 2.36; 95% CI: 1.13–4.95; p = 0.023). The incidence
of peri-implantitis (OR = 5.93; 95% CI: 2.75–12.8; p < 0.001) and the weighted mean
(WM) of marginal bone loss (WM difference = 0.75 mm; 95% CI: 0.18–1 0.3;
p < 0.05) were statistically significantly greater in the periodontally compromised
group, whereas there was no significant difference between the two groups for peri-
implant probing depth.
Conclusion: A history of periodontitis can be considered a significant risk factor for
incident implant failure, peri-implantitis, and greater marginal bone loss.

This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any
medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
© 2024 The Authors. Clinical Implant Dentistry and Related Research published by Wiley Periodicals LLC.

Clin Implant Dent Relat Res. 2024;1–27. wileyonlinelibrary.com/journal/cid 1

 17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
2 SERRONI ET AL.

KEYWORDS
dental implants, epidemiologic studies, longitudinal studies, periodontal diseases, risk ratios

Summary Box

What is known
The most recent systematic review regarding effects of a history of periodontitis on the inci-
dence of implant complications included only six prospective longitudinal studies.

What this study adds

Based on 12 prospective longitudinal studies including 4425 implants observed up to 20 years,
the overall risk of implant failure (loss) was 74% greater in patients with a history of periodonti-
tis, with a 2.4- and 2.6-fold greater risk after 5 and 10 years, respectively. The incidence of peri-
implantitis was four times greater (5 studies, 884 implants), with a difference also noted in mean
marginal bone loss, but not in peri-implant probing depth.

1 | I N T RO DU CT I O N smoking habits, diabetes mellitus and other systemic conditions) could

Implant therapy represents an effective long-term option with pre-
dictability supported by a robust body of evidence demonstrating high
implant survival rates even after more than 10 years.1,2
Peri-implant mucositis and peri-implantitis constitute two clinical
phenotypes that compromise the health of peri-implant tissues.3
Whereas peri-implant mucositis is confined to the mucosa represent-
ing a status of inflammation in response to microbes embedded in the
accumulated plaque, peri-implantitis is characterized by additional
resorption of the supporting bone.3 Evidence supports a close associ-
ation between the mainly Gram-negative bacteria associated with
periodontitis and the microbiome around the implants with clinical
signs of peri-implantitis,4,5 although both diversity and composition
may differ between periodontal and peri-implant microbiomes.6–11
Consequently, implementation of adequate infection control and
proper periodontal support therapy is fundamental prior to implant
therapy.12–14
Recent investigations have also illuminated how features of
implant site preparation, along with the macro- and micro-designs of
the implant surface and the prosthetic component, can play significant
roles in influencing the types of bacterial accumulation observed
around implants.15 Furthermore, it has been found that the products
of titanium dissolution play a key role as a modifying factor of the
peri-implant microbiome, limiting its biodiversity and enriching the
bacterial community of specific taxa (such as Veillonella), which are
predominantly found in peri-implant disease conditions.16
The development of periodontitis and peri-implantitis could be
17,18
characterized by the same sequence of events. The overlap of
several etiological, microbiological, histopathological, and clinical
aspects makes it reasonable to hypothesize that the risk for disease
may follow similar patterns in the two diseases and that, in turn, the
susceptibility to periodontitis can be reflected in a greater risk of
developing peri-implantitis. The commonality of the same main risk
predictors (e.g., poor oral hygiene, lack of regular maintenance,
support this hypothesis.13,19–24
Similarly, genetic predisposition to periodontitis of a subset of the
population can lead to an exaggerated and/or dysregulated inflamma-
tory response when exposed to pathogens.25,26 It is reasonable to
hypothesize that these individuals may exhibit a comparable immune
response in the presence of implants, potentially leading to more sig-
nificant damage to the inherently more susceptible peri-implant
tissues,27–29 exacerbated by a foreign body reaction.27,28,30
Systematic reviews and meta-analyses indeed have found an
association between a history of periodontitis and incidence of peri-
implantitis.31–35 However, the majority of studies included in the most
recent systematic review by Carra and colleagues were of cross-
sectional and retrospective designs with only six prospective cohort
studies.31 Only two meta-analyses published in 2007 and 2015,
respectively, included prospective studies exclusively,33,34 but only a
small subset of the included studies employed a controlled/
comparative design. Based on the then current body of literature, the
2017 European Federation of Periodontology/American Academy of
Periodontology World Workshop concluded there is a strong correla-
tion between the history of periodontitis and peri-implantitis,36 which
subsequent studies have confirmed by reporting a greater prevalence
of peri-implantitis among those with a history of periodontitis, such as
50% versus 15.9% overall,37 and OR = 3.64 (95% confidence interval
[CI]; 1.25–10.6) compared to no history.38 Nonetheless, a retrospec-
tive study among 99 patients with 221 implants and a history of peri-
odontitis followed for 10 years, a greater rate of implant failure was
found among patients with periodontitis Grade C, but no difference in
peri-implant prevalence was seen between periodontitis Stages III/IV
and I/II.39
Because it is challenging to successfully treat peri-implantitis once
established,40,41 it is of crucial importance to prevent its initiation and
progression, which requires knowledge of the pertinent risk factors.
Heitz-Mayfield, Heitz, and Lang suggested in 2020 a new tool named
implant disease risk assessment (IDRA), to help identify people at risk

SERRONI ET AL.
for peri-implantitis and the first of eight factors is “history of
periodontitis”.42
Based on the aforementioned considerations and the conclusions
from epidemiologic studies that emphasize the importance of pro-
spective studies to identify risk factors for a specific disease,43,44 our
aim was to explore whether a history of periodontitis represents a risk
factor for implant failure and development of peri-implantitis through
a systematic literature review of prospective longitudinal studies,
meta-analysis evaluated by trial sequential analysis (TSA),45 evaluation
of study bias by the Newcastle-Ottawa scale (NOS),46 and
evaluation of the certainty/quality of the evidence by the grading of
recommendations, assessment, development, and evaluations
(GRADE) approach.47
2 | MATERIALS AND METHODS
2.1 | Protocol and registration
The protocol for this review was developed to ensure the ability of
subsequently reporting the findings according to the preferred report-
ing items for systematic reviews and meta-analyses (PRISMA) guide-
lines and was registered on the online database named international
prospective register of systematic reviews (PROSPERO) with the
identification number CRD42022369454.
2.2 | Aims
The clinical questions for this systematic review were formulated
48
according to the PECOS framework.
The primary question was:
A. In systemically healthy adult human subjects (P = population),
does a history of periodontitis (E = exposure) increase the rate of
implant failure (O = Outcome #1) compared to no history of peri-
odontitis in periodontally healthy subjects (C = control/compari-
son) as explored by prospective cohort studies (S = study type)?
Secondary questions were:
B. In systemically healthy adult human subjects (P = population),
does a history of periodontitis (E = exposure), compared to no his-
tory of periodontitis in periodontally healthy subjects
(C = control/comparison), lead to greater incidence of peri-
implantitis (O = Outcome #2), greater peri-implant probing depth
(PIPD) (O = Outcome #3) or greater marginal bone loss (MBL)
(O = Outcome #4) as explored by prospective cohort studies
(S = study type)?
 Population (P): Systemically healthy adult human subjects hav-
ing received implant therapy
17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
3
 Exposure (E): A periodontally compromised dentition [due to a
history of (treated) periodontitis] at the time of implant
placement
 Comparison (C): Periodontally healthy dentition (with no history
of periodontitis) at the time of implant placement
Outcomes (O):
(#1) Implant failure (loss) rate (clinical and/or radiographic
assessment).
(#2) Incidence of peri-implantitis (clinical and/or radiographic
assessment).
(#3) Changes in MBL (radiographic assessment).
(#4) Changes in PIPD (clinical assessment).
2.3 | Eligibility criteria
All eligible studies must meet the following requirements: (1) original
prospective cohort studies; (2) participants ≥18 years of age with ≥1
dental implant(s); (3) ≥1 year of follow-up after prosthetic loading;
(4) ≥10 patients: ≥5 patients with a periodontally compromised denti-
tion [due to a history of (treated) periodontitis] (exposed) and ≥5
patients without a history of periodontitis (not exposed); (5) reporting
information on implant “survival or failure” meant as “presence or loss
(removal”) of the implant during the observation period; and (6) evalu-
ating ≥1 of the following implant outcomes: incidence of peri-
implantitis, increase in MBL, or magnitude of PIPD, in both patients
with and without a history of periodontitis. Study exclusion criteria
were as follows: (1) case reports; case series; and retrospective cohort,
case–control, and cross-sectional studies; (2) experimental in vivo,
ex vivo, and in vitro studies; (3) reviews, editorials, commentaries, etc.
2.4 | Information sources and search strategies
A systematic, comprehensive electronic search was conducted inde-
pendently by two reviewers (MS, GB) to identify potentially eligible
records in October 2022. The National Library of Medicine (MEDLINE
via PubMed), the Cochrane Library, and EMBASE were searched. The
literature search was performed using terms in ‘All Fields’ and Bool-
ean operators (AND, OR) combined: (“peri-implantitis” OR “periim-
plantitis”) AND (“periodontal diseases” OR “periodontitis” OR “risk
factors” OR “risk indicators”).
The identification phase was subsequently supplemented through
careful manual search carried out until January 2024 of the following
scientific journals: Journal of Clinical Periodontology, Journal of Peri-
odontology, International Journal of Periodontics and Restorative Den-
tistry, Journal of Oral and Maxillofacial Surgery, Clinical Oral Implants
Research, International Journal of Oral and Maxillofacial Implants, Jour-
nal of Implant Dentistry and Related Research, International Journal of

4 SERRONI ET AL.
Oral Implantology, European Journal of Oral Implantology, Journal
of Dental Research, Implant Dentistry and Journal of Oral Implantology.
No restrictions were applied regarding language or publication date.
2.5 | Study selection and data collection
After removing the duplicates, two reviewers (MS, GB) independently
evaluated the titles and abstracts, upon which the full text of the can-
didate articles was assessed for eligibility. Pertinent data were col-
lected, and cases of disagreement were resolved by discussion in a
joint session with a third author (AR) who calculated the screening
inter-reviewer agreement. For each study, when available, the follow-
ing data were extracted and recorded: first author name, year of publi-
cation, study country, study setting (private practice or university),
average age of each subgroup, mean duration of follow-up upon pros-
thetic loading, implant placement site location, implant brand, peri-
odontitis classification, definition of peri-implantitis, total number of
patients and implants for each group, incidence of peri-implantitis,
implant survival (or failure) rate, as well as clinical and radiographic
peri-implant parameters (PIPD, MBL, plaque index, modified plaque
index [mPI], bleeding on probing [BoP], modified bleeding index, gingi-
val index, full mouth plaque score and full mouth bleeding score). Five
authors were contacted and asked to provide missing data and a
response was received from 1 of them.
2.6 | Risk of bias and qualitative assessment
The qualitative evaluation of the eligible prospective studies was con-
ducted independently by two authors (MS, MHAS) by applying two
different tools (NOS46 and GRADE49).
2.6.1 | NOS
The NOS tool is specifically designed for assessing the quality of
nonrandomised studies in meta-analyses. Each study is evaluated
on eight aspects, divided into the following three domains: selec-
tion of study groups, comparability of groups, and assessment of
the outcome of interest. Each study can earn 1 star in the Selection
and Outcomes categories, respectively, and 0, 1, or 2 stars can be
allocated in the Comparability category. The maximum achievable
quality corresponds to a total of nine stars. NOS results were con-
verted according to the US Federal Agency for Healthcare Research
and Quality (AHQR) standards in the following categories: 3 or
4 stars in the Selection domain and 1 or 2 stars in the Comparability
domain, and 2 or 3 stars in the Outcome domain corresponds to
‘Good’ quality; 2 stars in the Selection domain and 1 or 2 stars in
Comparability and 2 or 3 stars in Outcome domain corresponds to
‘Fair‘quality; 0 or 1 star in the Selection domain or 0 stars in the
Comparability domain or 0 or 1 stars in the Outcome domain corre-
sponds to ‘Poor‘quality.50
17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
2.6.2 | GRADE
Starting from a ‘low’ certainty/quality due to the inclusion of only
studies of the prospective cohort study design with no randomized
controlled trials (RCTs), five factors were used for downgrading (risk
of bias, inconsistency, imprecision, indirectness, and publication bias),
and three were used for upgrading (magnitude of effect, dose–
response gradient, and plausible confounding effect), if appropriate,
the certainty of evidence.49 Imprecision was evaluated using the
Required Information Size (RIS) obtained from the TSA. The certainty/
quality of the evidence was finally considered as high, moderate, low,
or very low. Methods and recommendations described in sections 8.5
and 8.7, and chapters 11 and 12, of the Cochrane handbook for sys-
tematic reviews of interventions were followed.51 GRADEpro GDT
software was then used to create a summary of findings (SoF) table,
including assessment of the certainty/quality of the body of evidence
(GRADEpro GDT 2021), in which all decisions to down- or upgrade
the certainty/quality of studies were justified using footnotes.
2.7 | Data synthesis and summary of findings
(SoF) table
First, all groups of patients with a history of periodontitis classified
into different types and severity according to Armitage et al. or Page
et al.52,53 were aggregated into a single test group (periodontally com-
promised patients [PCP] group) and were compared with the control
group (periodontally healthy patients [PHP] group) of patients without
a history of periodontitis.
Regarding failure and peri-implantitis incidence rates, the logarith-
mic risk ratio (logRR) was calculated for each study and the global
effect measure from a random-effects model with restricted
maximum-likelihood estimators was estimated. Forest plots including
95% CIs and weights for each study were generated to present
results. Due to the wide range of follow-up durations in the studies,
stratified subgroup analyses were conducted for ≤5 years and
>5 years duration.
Mean differences in MBL and PIPD between PHP and PCP were
estimated for each study and the weighted mean difference (WMD)
as the global effect measure in a random-effects model with corre-
sponding Z statistics, p-values, and 95% CIs were calculated for all
studies and for each duration stratum, respectively. Subsequently,
annual MBL and PIPD rates were calculated to compensate for the
studies' different follow-up durations, and the same analyses were
conducted.
Cochran's Q test was applied for the heterogeneity analysis. The
2
I index score was also calculated, representing the quantity of
between-studies variability compared to the total variability. Funnel
graphs were created to visually assess potential publication bias and
Egger's test was used to assess such bias in the meta-analyses via fun-
nel plot asymmetry. The level of significance used in the analysis was
5% (α = 0.05). Metafor and gemtc packages from the 2018 R 3.5.1
software package were used.54

SERRONI ET AL.
3 | RESULTS
3.1 | Study selection
During the identification phase, 1196 articles were generated from
PubMed (MEDLINE), 607 from Cochrane Library, 1498 from EMBASE
(Figure 1). After elimination of duplicates, titles and abstracts from 3132
records were screened and 36 articles underwent full-text evaluation.
Twenty-seven studies were excluded primarily because of their study
design (cross-sectional or retrospective) or due to the absence of a com-
parison between an exposed group (with a history of periodontitis) and a
non-exposed group (without a history of periodontitis). In addition, five
articles were identified by manual search and subsequently assessed for
eligibility. Finally, 14 articles met the aforementioned eligibility criteria
and were included for data collection.55–68
All eligible studies were included in the qualitative and quantita-
tive analyzes. Specifically, two papers reported the results at 10 years
of follow-up of the same cohort with part 1 reporting radiographic
results of MBL and implant survival rate and part 2 reporting the clini-
cal parameters,65,67 and two other papers reported results from the
same cohort after 10 and 20 years of follow-up, respectively.64,66
Therefore, results from 14 reports on a total of 12 cohorts were ana-
lyzed; and their characteristics are displayed in Table 1.
3.2 | Quality assessment
The NOS tool for prospective cohort studies was applied to assess
the quality and risk of bias, respectively (Table S1). Based on the NOS
star scores, eight studies were of ‘Good’ quality as they obtained 3 or
FIGURE 1 Study selection. (Page et al. 2021; http://www.prisma-statement.org/).
17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
5
4 stars in the Selection domain, 1 or 2 stars in the Comparability
domain and 2 or 3 stars in the Results domain.55–57,59,60,64–68 The
remaining four studies were judged to be of ‘Poor’ quality because
they did not earn any stars in the Comparability domain.58,61–63 Eight
studies were classified as having a ‘Low’ Risk of Bias,55–57,59,60,64–68
while four were assigned a ‘High’ Risk of Bias58,61–63 (Table S1).
The results of the application of the GRADE approach regarding
the outcomes-centered body of evidence and the pooled summary
estimates applied in an overall evaluation of the certainty/quality of
the evidence for all four outcomes of interest (implant failure, peri-
implantitis incidence, MBL, and PIPD) are illustrated in the results
summary table (Table 2).
In particular, a detailed analysis conducted by the GRADE tool
deduced that the results attesting to the correlation between implant
failure (both overall and after follow-up durations of both ≤5 and
>5 years, respectively) and a history of periodontitis is corroborated
by ‘Low’ quality level of evidence. At the same time, a ‘Very low’ level
of quality of evidence was observed in the overall analyses of out-
comes related to incidence of peri-implantitis, MBL, and PIPD.
3.3 | Characteristics of included studies
3.3.1 | Study designs and test group periodontitis
case definitions
All studies were prospective longitudinal studies that reported results
from 12 studies that included 1464 patients with 4425 implants55–68
(Table 1). All studies compared one control group of PHPs with ≥1
test groups of PCPs.
 6

TABLE 1 Characteristics of all the included prospective cohort studies (n = 12 studies/14 reports; n = 1464 pts; n = 4425 implants at last visit).a

(1) #Pts (F/M)/# (1) Mean age (SD, Range) (2) #

implants Patients/# implants Implant: (1) Brand

Article # author (year) reference # FU Mos (2) # Dropouts Periodontitis Smokers

country (setting) (±SD) (Pts/implants) PHP PCP definition % Pts (2) Location
Total (Mos/yrs) 89.8 (1) 1464 (NR/NR)/ (1) (NR) (1) (NR) NR
(7.5) 4425 (2) 647/1617 (2) 817/2808
(2) NR/NR
(#1) Karoussis et al. (2003)59 120 (1) 53(NR)/112 (1) NR (1) NR CP52 22.6% (1) Straumannb
Switzerland (Univ. & Priv.practice) (2) 0/0 (2) 45/91 (2) 8/21 (2) NR
(#2) Mengel et al. (2005)62 36 (1) 39(21/18)/150 (1) 31 (NR) (1) GAgP: 32 GAgP52 0% (1) Osseotite MK II,
Germany (Univ.) (2) 0/0 (2) 12/30 (NR) CP52 Nobel Biocarec
(1) CP: 34 (NR) (2) max & mand
(2) GAgP:
12/43
(2) CP: 15/77
(#3) Mengel et al. (2007a)61 120 (1) 10(8/2)/43 (1) NR (1) NR (31–44) Rapidly progres. NR (1) Nobel Biocarec
Germany (Univ.) (2) 0/0 (20–51) (2) 5/36 periodontitis53 (2) max & mand
(2) 5/7
(#4) Mengel et al. (2007b)63 36 (1) 17(8/9)/54 (1) 31 (NR) (1) 34 (NR) GAgP52 0% (1) Osseotite, BIOMET/3id
Germany (Univ.) (2) 0/0 (2) 8/13 (2) 9/41 CP52 (2) max & mand
(#5) Gatti et al. (2008)57 60 (1) 56(39/17)/227 (1) 40(18–61) (1) MP:56 (42– PSR69 PHP: 20% (1) Straumann,b Nobel Bio-care,c Zimmer
Italy (Priv. practice) (2) 6/NR (2) 27/72 70) MP: 43% Dental,e Mathys,f Dentsply Friadentg
(1) SP: 56 (35– SP: 19% (2) max & mand
85)
(2) MP: 5/26
(2) SP: 24/129
(#6) De Boever et al. (2009)55 48.1 (1) 194(102/92)/513 (1) 48.7 (1) GAgP: NR CP52 PHP: NR (1) Straumann SLA/TPSb
Belgium (Univ.) (±25.9) (2) 27/NR (±13.1) (1) CP: 60.1 ( GagP52 CP: 13% (2) max & mand
(2) 110/261 ±8.1) GAgP:
(2) GAgP: 25%
16/59
(2) CP: 68/193
(#7) Roccuzzo et al. (2010)67/ 120 (1) 101(NR)/246 (1) 45 (±13) (1) MP: 49 ( CP52 NR (1) Straumann TPSb
(2012)65* (2) 11/18 (2) 28/61 ±15.3) (2) NR
Italy (Priv. practice) (1) SP: 44 (
±8.6)
(2) MP: 37/95
(2) SP: 36/90
(#8) Levin et al. (2011)60 54.4 (1) 717(444/273)/ (1) 46.05 (1) MP: 53.77 ( MP52 PHP: (1) NR
Israel (Univ.) (±35.6) 2259 (±8.4) ±9.3) SP52 11.3% (2) NR
(2) NR/NR (2) 283/747 (1) SP: 54.93 ( MP: 10.7%
±14.9) SP: 19.3%
SERRONI ET AL.

17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
 TABLE 1 (Continued)

(1) #Pts (F/M)/# (1) Mean age (SD, Range) (2) #

implants Patients/# implants Implant: (1) Brand
SERRONI ET AL.

Article # author (year) reference # FU Mos (2) # Dropouts Periodontitis Smokers

country (setting) (±SD) (Pts/implants) PHP PCP definition % Pts (2) Location
(2) MP:
149/447
(2) SP:
285/1065
(#9) Jiang et al. (2012)58 24 (1) 60(39/21)/276 (1) 42 (NR) (1) 37 (NR) CP52 NR (1) NR
China (NR) (2) 0/0 (2) 30/127 (2) 30/149 (2) max & mand
(#10) Swierkot et al. (2012)68 99 (1) 53(NR)/179 (1) 38.6 (1) 39.6 (27– GAgP52 26.4% (1) NR
Germany (Univ.) (2) 0/0 (25–57) 56) (2) max & mand
(2) 18/30 (2) 35/149
(#11) Roccuzzo et al. (2014)66/ 240 (1) 84(NR)/172 (1) 63.4 (1) MP: 70.6 ( CP52 PHP: (1) Straumann SLAb
(2022)64* (2) 39/125 (±12.1) ±9.7) 18.2% (2) NR
Italy (Priv. practice) (2) 22/39 (1) SP: 71.0 ( MP: 13.8%
±7.8) SP: 18.2%
(2) MP: 29/61
(2) SP: 33/72
(#12) Degidi et al. (2016)56 120 (1) 80(NR)/194 (1) 53.1 (1) 53.1 (15.7) NR 28.8% (1) Xive Dentsplyg
Italy (Priv. practice) (2) 30/78 (±15.7) (2) 21/55 (2) NR
(2) 59/139

Abbreviations: #, number; CP, chronic periodontitis; F/M, female/male; FU, follow-up; GAgP, generalized aggressive periodontitis; mand, mandible; max, maxilla; Mos, months; MP, moderate periodontitis; NR,
not reported; PCP, periodontally compromised patients; PHP, periodontally healthy patients; Priv., private; progres., progressive; PSR, periodontal screening and recording index; Pts/pts, patients; SLA, sand-
blasted and acid-etched; SP, severe periodontitis; TPS, titanium-sprayed surfaces; Univ., university; Yrs, years.
a
Reports from the longest follow-up duration were used in case of ≥1 report from the same study.
b
Straumann Group AG, Waldenburg, Switzerland.
c
MK II, Brånemark System, Nobel Biocare, Gothenburg, Sweden.
d
Zimmer Biomet® (Palm Beach Gardens, Florida, USA).
e
Zimmer Dental (Carlsbad, California, USA).
f
Mathys (Bettlach, Switzerland).
g
Dentsply Friadent (Mannheim, Germany).
7

17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

8 SERRONI ET AL.
Six studies considered only one test group.56,58,59,61,63,68 Karous-
sis et al. and Jiang et al. recruited patients with a history of chronic
(not further specified) periodontitis, 58,59
Mengel et al. 61
considered
patients with a history of rapidly progressive periodontitis, Mengel
et al. and Swierkot et al. included patients with a history of general-
ized aggressive periodontitis,63,68 and Degidi et al. recruited patients
56
with a history of periodontitis (not further specified).
On the other hand, six articles regarding four cohorts included
two test groups, one with moderate and another with severe chronic
periodontitis.57,60,64–67 The remaining two studies also involved two
test groups, one of which comprised patients with generalized aggres-
sive periodontitis, whereas the second groups differed: Mengel et al.
62
examined patients with generalized chronic periodontitis, while De
Boever's group studied patients with adult chronic periodontitis.55,62
In 10 of the 12 studies, the periodontitis type was assigned
according to the classification by Armitage et al.,52 whereas Mengel
et al.61 applied the definition rapidly progressing periodontitis accord-
ing to Page and Kornman53 and Gatti et al.69 used the periodontal
screening and recording (PRS) index tool.
3.3.2 | Study duration
The study duration ranged from 2 to 20 years (Table 1). The studies
by Jiang et al.,58 Gatti et al.,57 and Swierkot et al.68 followed patients
for periods of 24, 60, and 99 months, respectively. Two studies
reported results from a mean follow-up of 48.1 (±25.9) and 54.4
55,60
(±35.6) months, respectively, whereas two studies lasted
3-years.62,63 Four research teams reported results from the 10-year
follow-up visit,56,59,61,65–67 and one study reported results after
64,66
20 years follow-up.
3.3.3 | Case definitions: peri-implantitis
The criteria used to define peri-implantitis differed among studies. For
instance, De Boever et al.55 determined the presence of peri-
implantitis using parameters that were not explicitly defined. In con-
trast, three studies provided clear threshold values that facilitated the
diagnosis of peri-implantitis.57,59,68 Meanwhile, Degidi et al.56 relied
on the definition of peri-implantitis established by Albrektsson & Isi-
dor.70 In the study by Roccuzzo et al.,64,66 the definition of peri-
3
implantitis was applied according to Renvert and co-authors. In one
study, a definition of peri-implantitis is not presented,65,67 but a
cumulative interceptive supportive therapy (CIST) depending on the
type of peri-implant disease is described.71 Finally, five studies did not
mention peri-implantitis as an outcome. 58,60–63
3.3.4 | Incidence of peri-implantitis and other peri-
implant parameters
The incidence of peri-implantitis was reported in five
cohorts56,57,59,64,68 (Table 4). Nine studies recorded the mean values
17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
of MBL at follow-up,55–57,59,61–63,67 while five studies reported the
mean PIPD values.56,59,62,63,65 Roccuzzo et al. recorded the number of
implants with >1 site with PIPD ≥6 mm and, secondarily, the percent-
age of peri-implant sites with MBL ≥3 mm, full mouth plaque score,
and full mouth bleeding score.66
Two studies recorded the mPI and the modified bleeding
index;58,59 three studies the gingival index and PI scores;61–63,72 one
study full mouth plaque and bleeding scores, respectively.66
One study reported the overall BoP and the overall implant plaque
score, without distinguishing between test and control groups.64
Finally, one study reported information about PI and BoP in the test
and control groups.65 Five studies did not report data on any index of
bleeding or plaque.55–57,60,68
3.4 | Quantitative synthesis of the evidence: meta-
analysis and TSA
All reports were included for quantitative synthesis. Quantitative and
qualitative data from the studies are shown in (Table 1).
3.4.1 | Implant failure rate (Outcome #1)
All 14 articles (reporting on 12 cohorts) involving a total number
of 4425 implants (1617 in PHP and 2808 in PCP) provided infor-
mation regarding implant failure,55–68 defined as loss resulting
from complete spontaneous loosening or mobility of the implant
that no longer allows function during the observation period, as
determined by clinical and/or radiographic observation (Table 3).
Results of the meta-analysis indicated that the risk of failure was
statistically significantly 74% greater in PCP compared to PHP
(RR = 1.74; 95% CI: 1.25–2.44; p = 0.001) (Figure 2A). The Gal-
braith plot showed high consistency (I2 = 0%) between studies
(Figure 2B), and the funnel plot showed a high level of symmetry
( p = 0.554, Egger's test) indicating low risk of publication bias
(Figure 2C).
In the TSA evaluating all 12 cohorts, the RIS (n = 688 implants)
was exceeded (4425 implants: 1515 in PHP and 2657 in PCP), sup-
porting both the significance of the difference in implant failure rates
between the two groups as well as the conclusiveness of the meta-
analytic results (Figure 2D).
In the following, results of sub-analyses of the implant failure rate
stratified by study duration are reported.
Study duration ≤5 years
Sub-analysis of the six studies with follow-up ≤5 years55,57,58,60,62,63
showed that the risk of failure was statistically significantly 62%
greater in the PCP group than the PHP group (RR = 1.62; 95% CI:
1.71–2.37; p = 0.013) (Figure 3A). The symmetry observed in the fun-
nel plot indicated no risk of publication bias (Figure 3B). In the TSA
evaluating the six studies, the required information size RIS (n = 703
implants) was reached (3479 implants:1250 in PHP and 2229 in PCP).
The significance of the difference between the two groups was
 SERRONI ET AL.

T A B L E 2 Summary of findings (SoF) from GRADE assessment of the certainty/quality of the evidence for the four peri-implant disease outcomes (#1–#4) explored in people with a history of
periodontitis versus no history of periodontitis at implant placement based on the respective prospective longitudinal studies.

# # Patients/# Summary estimates RR or Risk Magni-tude

Outcome # Studies implants mean (95% CI) p value of Bias Inconsistencya Indirectness Imprecision of Effect Certainty Importance
LL
(#1) Implant failure 12 1464/4425 1.74 (1.25; 2.44), Not Not serious Not serious Not serious Absent ◯◯ Critical
rate overall p = 0.001 serious (I2 = 0%) LOW
LL
(#1) Implant failure 6 1083/3479 1.62 (1.71; 2.37), Not Not serious Not serious Not serious Absent ◯◯ Critical
rate ≤5y p = 0.013 serious (I2 = 0%) LOW
LL
(#1) Implant failure 6 381/946 2.36 (1.12; 4.53), Not Not serious Not serious Not serious Absent ◯◯ Critical
rate >5y p = 0.023 serious (I2 = 0%) LOW
LL
(#1) Implant failure at 5 367/847 2.61 (1.19; 5.81), Not Not serious Not serious Not serious Absent ◯◯ Critical
10y p = 0.018 serious (I2 = 0%) LOW
L
(#2) Peri-implantitis 5 326/884 4.09 (1.93; 8.58), Not Moderate Seriousb Seriousc Largee ◯◯◯ Critical
incidence overall p < 0.001 serious (I2 = 52.8%) VERY LOW
L
(#2) Peri-implantitis 3 256/558 8.58 (4.06; 18.00), Not Not serious Seriousb Seriousc Largee ◯◯◯ Critical
incidence 10y p < 0.001 serious (I2 = 0%) VERY LOW
L
(#3) MBL (mean, total) 6 303/914 0.75 mm (0.18; 1.31), Not Serious Not serious Seriousd Absent ◯◯◯ Critical
p < 0.05 serious (I2 = 92.5%) VERY LOW
L
(#3) MBL (mean/year) 6 303/914 0.13 mm (0.02; 0.22), Not Serious Not serious Seriousc Absent ◯◯◯ Critical
p < 0.05 serious (I2 = 92.3%) VERY LOW
L
(#4) PIPD (mean, total) 5 300/756 0.33 mm ( 0.26; 0.91), Not Serious Not serious Seriousc Absent ◯◯◯ Critical
p = 0.273 serious (I2 = 89.8%) VERY LOW
L
(#4) PIPD (mean/year) 5 300/756 0.03 mm ( 0.06; 0.12), Not Serious Not serious Seriousc Absent ◯◯◯ Critical
p = 0.485 serious (I2 = 89.3%) VERY LOW

Note: Outcome #1, implant failure; Outcome #2, peri-implantitis incidence rate; Outcome #3, marginal bone loss (MBL); Outcome #4, peri-implant probing depth (PIPD). Bold font indicates statistical significance
at p < 0.05.
Abbreviations: #, number; CI, Confidence interval; GRADE, Grading of Recommendations Assessment, Development and Evaluation; MBL, radiographic marginal bone loss; OR, odds ratio; PIPD, peri-implant
probing depth; PPD, periodontal probing depth; RIS, required information size; RR, risk ratio.
a
Based on levels of heterogeneity (I2; %).
b
Differences in outcomes measures.
c
RIS criterion was not met.
d
RIS criterion was not met and the 95% CI overlaps no effect.
e
RR >2. Quality of evidence increases 1 level.
9

17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
 17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
10 SERRONI ET AL.

TABLE 3 Implant failure by history of periodontitis (n = 12 studies/14 reports; n = 4425 implants at last visit).

# Failed implants/ # implants (total) (# failed implants per year/%

implants failed per year)
Article # author (year) reference
# country (setting) FU Mos (yrs) #Pts/# implants PHP PCP
Total 89.8 1464/ 45/1617 (2.8%) 135/2808 (4.8%)
(7.5) 4425
(#1) Karoussis et al. (2003)59 120 53/112 2/91 (2.2%) 3/21 (14.2%)
Switzerland (Univ. & Priv. practice) (10) (0.2/0.2%) (0.3/1.4%)
(#2) Mengel et al. (2005)62 36 39/150 0/30 (0%) 2/120 (1.7%)
Germany (Univ.) (3) (0) (1.5/0.6%)
(#3) Mengel et al. (2007a)61 120 10/43 0/7 (0%) 3/36 (8.3%)
Germany (Univ.) (10) (0) (0.3/0.8%)
(#4) Mengel et al. (2007b)63 36 17/54 0/13 (0%) 1/41 (2.4%)
Germany (Univ.) (3) (0) (0.3/0.8%)
(#5) Gatti et al. (2008)57 60 56/227 0/72 (0%) 2/155 (1.3%)
Italy (Priv. practice) (5) (0) (0.4/0.3%)
(#6) De Boever et al. (2009)55 48.1 194/513 8/261 (3.1%) 16/252 (6.3%)
Belgium (Univ.) (4.0) (2/8%) (4/1.6%)
(#7) Roccuzzo et al. (2010)67/(2012)65* 120 101/246 2/61 (3.3%) 16/185 (8.6%)
Italy (Priv. practice) (10) (0.2/0.3%) (1.6/0.9%)
(#8) Levin et al. (2011)60 54.4 717/2259 23/747 (3.1%) 70/1512 (4.6%)
Israel (Univ.) (4.5) (5.1/0.7%) (15.6/1.0%)
(#9) Jiang et al. (2012)58 24 60/276 3/127 (2.4%) 6/149 (4.0%)
China (NR) (2) (1.5/1.2%) (3/2.0%)
(#10) Swierkot et al. (2012)68 99 53/179 0/30 (0%) 6/149 (4.0%)
Germany (Univ.) (8.3) (0) (0.7/0.5%)
(#11) Roccuzzo et al. (2014)66/(2022)64 240 84/172 2/39 (5.1%) 10/133 (7.5%)
Italy (Priv. practice) (20) (0.1/0.3%) (0.5/0.4%)
(#12) Degidi et al. (2016)56 120 80/194 5/139 (3.6%) 3/55 (5.5%)
Italy (Priv. practice) (10) (0.5/0.4%) (0.3/0.6%)

Abbreviations: #, number; F/M, female/male; FU, follow-up; GAgP, generalized aggressive periodontitis; GCP, generalized chronic periodontitis; mand,
mandible; max, maxilla; MBL, (radio-graphic) marginal bone loss; Mos, months; MP, moderate periodontitis; NR, not reported; PCP, periodontally
compromised patients; PHP, periodontally healthy patients; PPD, periodontal probing depth; Priv. practice, private practice; PSR, periodontal screening and
recording index; rapidly progres. perio, rapidly progressive periodontitis; SLA, sand-blasted and acid-etched; SP, severe periodontitis; TPS, titanium-sprayed
surfaces; Univ., university.

ascertained, and the conclusiveness of the meta-analytic results was was ascertained and the conclusiveness of the meta-analytic results
robust (Figure 3C). was robust (Figure 4C).

Study duration >5 years Study duration of 10 years

Similarly, sub-analysis of only the six studies with follow-up duration
of >5 years56,59,61,64,67,68 calculated a RR of 2.36 (95% CI: 1.12–4.53;
p = 0.023) indicating that the probability of failure was statistically
significantly 126% greater in PCP compared to PHP (Figure 4A). The
hypothesis of lack of publication bias was accepted ( p = 0.848,
Egger's test) as shown by the symmetry of the funnel plot (Figure 4B).
In the TSA evaluating the six studies, the required information size RIS
(n = 636 implants) was reached (946 implants: 367 in PHP and 579 in
PCP) so the significance in the difference between the two groups
Sub-analysis of only the five studies with 10 years follow-
up56,59,61,66,67 showed RR = 2.61 (95% CI: 1.19–5.81; p = 0.018)
indicating that the risk of failure was statistically significantly 161%
greater in the PCP group than the PHP group (Figure 5A). The
hypothesis of lack of publication bias was accepted ( p = 0.857,
Egger's test) as shown by the symmetry of the funnel plot
(Figure 5B). In the TSA evaluating the five studies, the RIS
(n = 636) was reached (847 implants: 352 in PHP and 495 in PCP).
The significance in the difference between the two groups was
17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
11

Legend on next page.

SERRONI ET AL.

FIGURE 2
 17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
12 SERRONI ET AL.

ascertained, and the conclusiveness of the meta-analytic results
was robust (Figure 5C).
3.4.2 | Peri-implantitis incidence (Outcome #2)
Information regarding the incidence rate of peri-implantitis was pro-
vided by five studies that included 326 patients with a total of
884 implants at the last visit, namely 371 in the PHP and 513 in the
PCP groups56,57,59,64,68 (Table 4). The forest plot in Figure 6A shows
that the peri-implantitis incident rate was statistically significantly four
times greater in the PCP group compared to the PHP group
(RR = 4.09; 95% CI: 1.93–8.58; p < 0.001).
The heterogeneity was moderate (I2 = 52.8%) and no specific
study contributed exceedingly thereto, as shown by the Galbraith
plot of inter-study consistency for incidence of peri-implantitis
(Figure 6B). The hypothesis of non-asymmetry was accepted
( p = 0.569, Egger's test), indicating the absence of publication bias
(Figure 6C).
Considering all five studies including 326 patients and
884 implants, the significance of the differences in the incidence of
peri-implantitis is reliable and robust as the z-curve crossed both the
5%-conventional and the adjusted boundaries (Figure 6D). However,
because the RIS (n = 1726 implants) was not reached, the results of
the meta-analysis are highly probable, but not conclusive.
In this case, a further sub-analysis was not conducted for the
stratification of study duration (i.e., ≤ or >5 years) since four out of
the five studies had a follow-up duration exceeding 5 years, while
1 study had a follow-up exactly 5 years long.
Study duration of 10 years
Sub-analysis of only the three studies with 10 years follow-up56,59,66
showed RR = 8.58 (95% CI: 4.06–18.00; p < 0.001), indicating that
the peri-implantitis incident rate was statistically significantly 8.5
times greater in the PCP group compared to the PHP group
(Figure 7A). Galbraith plot of inter-study consistency showed no het-
erogeneity (I2 = 00.0%) (Figure 7B).
The hypothesis of lack of publication bias was accepted
( p = 0.747, Egger's test) as shown by the symmetry of the funnel plot
(Figure 7C). In the TSA evaluating the three studies, significance in the
difference between the two groups was ascertained. However,
the required information size RIS (n = 852 implants) was not reached
(558 implants: 284 in PHP and 274 in PCP), so the results of the
meta-analysis are inconclusive, but highly probable (Figure 7D).
3.4.3 | MBL changes (Outcome #3)
Eight reports provided data about MBL at patient-level,55–57,59,61–
63,67
however two studies were excluded from the analysis due to the
absence of the SD.55,59 Conventional meta-analysis reported values
of WMD for MBL that were significantly greater in the test (PCP)
group than in the control group (PHP) (WMD = 0.75 mm; 95% CI:
0.18–1.3; p < 0.05) (Figure 8A). However, due to outlying greater
values reported by two studies,57,61 the graphs show high levels of
both heterogeneity (I2 = 92.5%) (Figure 8B) and asymmetry
(p = 0.001, Egger's test) (Figure 8C).
The TSA revealed that using the currently available sample size
(n = 303 implants), the z-curve crossed the 5% conventional and
adjusted boundaries (Figure 8D), indicating that the significance of
WMD for annualized MBL between the PCP and the PHP groups was
reliable. However, the RIS (n = 401 implants) was not achieved and
hence, the conclusiveness of the results of the present meta-analysis
could not be supported.
Annualized mean MBL
In order to mitigate the heterogeneity in study duration, the mean
annualized MBL was calculated (total MBL/number of years follow-up
duration) and a new meta-analysis was conducted (Figure 9A). Signifi-
cantly greater values of annual MBL for the test group (PCP) com-
pared to the control group (PHP) was till reported, showing the
benefit of the absence of a history of periodontitis to moderate
the annual MBL progression, although the magnitude was much smal-
ler (WMD = 0.13 mm; 95% CI: 0.04–0.22; p < 0.01). The Galbraith
plot revealed high level of heterogeneity between studies
(I2 = 92.5%) (Figure 9B) but the funnel plot for potential publication
bias analysis for annualized MBL now showed sufficient symmetry
(p = 0.149) to accept the hypothesis of lack of publication bias
(Figure 9C).
It is already known from the total MBL analysis that the RIS was
not reached (Figure 8D). Since the RIS was not reached with all five
available studies combined, and any subanalyses or stratifications
would further diminish the statistical power, no further analyses were
conducted.
3.4.4 | PIPD changes (Outcome #4)
Five reports provided data regarding PIPD at patient-level.56,59,62,63,65
The meta-analysis calculated a greater value of WMD for PIPD

F I G U R E 2 Overall incident implant failure rate (n = 12 studies (14 reports); n = 1617 PHP + 2808 PCP = 4425 implants at last visit).
(A) Meta-analysis of LogRR for failure rate. Log RR >0 (equivalent to RR >1) indicates that the failure rate was greater in the PCP group than in
the PHP group. (B) Galbraith plot of inter-study consistency shows high consistency (I2 = 0%) (no heterogeneity) between studies. (C) Funnel plot
of LogOR for potential publication bias shows a high level of symmetry ( p = 0.540, Egger's test) with no publication bias risk. (D) TSA evaluating
the implant failure rates comparing PCP to PHP. The RIS (n = 688) was surpassed (n = 1587 implants).
Abbreviations: CI, confidence interval; EC, events (failed implants) in the control group (PHP); ET, events (failed implants) in the test group (PCP);
PCP, periodontally compromised patients; PHP, periodontally healthy patients; RIS, required information size; TSA, trial sequential analysis; TT,
total number of implants in the test group (PCP); TC, total number of implants in the control group (PHP).
 17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SERRONI ET AL. 13

F I G U R E 3 Implant failure rate according to studies with ≤5 years follow-up (n = 6 studies (6 reports); n = 1250 PHP + 2229 PCP = 3479
implants at last visit). (A) Meta-analysis of LogRR for failure rate. Log RR >0 (equivalent to RR >1) indicates that the failure rate was greater in the PCP
group than in the PHP group. (B) Funnel plot of LogRR for potential publication bias shows a good level of symmetry (p = 0.937, Egger's test) with no
publication bias risk. (C) TSA evaluating the implant failure rates comparing PCP to PHP. The RIS (n = 703) was surpassed (n = 3479 implants).
Abbreviations: CI, confidence interval; EC, events (failed implants) in the control group (PHP); ET, events (failed implants) in the test group (PCP); PCP,
periodontally compromised patients; PHP, periodontally healthy patients; RIS, required information size; TSA, trial sequential analysis; TT, total
number of implants in the test group (PCP); TC, total number of implants in the control group (PHP).

(WMD = 0.33 mm; 95% CI: 0.26–0.91; p = 0.273) in the PCP group results between the studies, as reflected in the calculated high level of
than in the PHP group, but statistical significance was not reached heterogeneity (I2 = 89.8%) (Figure 10B), but Egger's test did not reveal
(Figure 10A). Visual inspection of the forest plot reveals highly varying any signals of publication bias shown in the funnel plot (Figure 10C).
 17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
14 SERRONI ET AL.

F I G U R E 4 Implant failure rate according to studies with >5 years follow-up (n = 6 studies (8 reports); n = 367 PHP + 579 PCP = 946 implants
at last visit). (A) Meta-analysis of LogRR for failure rate. Log RR >0 (equivalent to RR >1) indicates that the failure rate was greater in the PCP group
than in the PHP group. (B) Funnel plot of LogRR for potential publication bias shows a good level of symmetry (p = 0.937, Egger's test) with no
publication bias risk. (C) TSA evaluating the implant failure rates comparing PCP to PHP. The RIS (n = 636) was surpassed (n = 946 implants).
Abbreviations: CI, confidence interval; EC, events (failed implants) in the control group (PHP); ET, events (failed implants) in the test group (PCP);
PCP, periodontally compromised patients; PHP, periodontally healthy patients; RIS, required information size; TSA, trial sequential analysis; TT, total
number of implants in the test group (PCP); TC, total number of implants in the control group (PHP).

Results of TSA for PIPD using the current sample size (n = 290 implants) between the PCP and PHP groups. Moreover, neither the RIS (n = 1444
showed that the z-curve did not cross the 5% conventional nor the implants) nor the futility lines were reached, confirming the inconclusive-
adjusted boundary line, demonstrating no significance in WMD for PIPD ness of the meta-analytic results (Figure 10D).
 17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SERRONI ET AL. 15

F I G U R E 5 Implant failure rate according to studies with 10 years follow-up (n = 5 studies; n = 352 PHP + 495 PCP = 847 implants at last
visit). (A) Meta-analysis of LogRR for failure rate. Log RR >0 (equivalent to RR >1) indicates that the failure rate was greater in the PCP group than
in the PHP group. (B) Funnel plot of LogRR for potential publication bias shows a good level of symmetry (p = 0.857, Egger's test) with no
publication bias risk. (C) TSA evaluating the implant failure rates comparing PCP to PHP. The RIS (n = 636) was surpassed (n = 847 implants).
Abbreviations: CI, confidence interval; EC, events (failed implants) in the control group (PHP); ET, events (failed implants) in the test group (PCP);
PCP, periodontally compromised patients; PHP, periodontally healthy patients; RIS, required information size; TSA, trial sequential analysis; TT,
total number of implants in the test group (PCP); TC, total number of implants in the control group (PHP).
 17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
16 SERRONI ET AL.

TABLE 4 Incidence of peri-implantitis by history of periodontitis (n = 5 studies; n = 326 pts; n = 884 implants at last visit).

# Implants w/peri-implantitis/#
implants (%) [total] (# implants w/peri-
implantitis per year/% implants per year
Article (#) author (year) reference
# country (setting) FU Mos (yrs) Peri-implantitis case definition PHP PCP
Total Various
(#1) Karoussis et al. (2003)59 120 PIPD ≥5 mm 5/91 (5.5%) 8/21 (38.1%)
Switzerland (Univ. & Priv. practice) (10) BoP (0.5/0.6%) (0.8/3.8%)
MBL
(#5) Gatti et al. (2008)57 60 MBL >2 mm > prior 0/72 (0%) 29/155 (18.7%)
Italy (Priv. practice) (5) X-ray assessment; (0/0%) 4/155 (2.6%)
infection sign (e.g., pus); (0.8/0.5%)
PIPD >5 mm
(#10) Swierkot et al. (2012)68 99 PIPD >5 mm (±BoP) & annual MBL >0.2 mm 3/30 (10%) 39/149 (26.2%)
Germany (Univ.) (8.3) (0.4/1.2%) (4.7/3.2%)
(#11) Roccuzzo et al. (2022)64 240 Bone loss >3 mm, bone loss >3 mm and PIPD >6 mm 7/39 (17.9%) 45/133 (33.8%)
Italy (Priv. practice) (20) (0.4/0.9%) (2.3/1.7%)
(#12) Degidi et al. (2016)56 120 Infection (pus) & MBL55 3/139 (2.2%) 13/55 (23.6%)
Italy (Priv. practice) (10) (0.3/0.2%) (5.5/2.4%)

Abbreviations: #, number; BoP, bleeding on probing; CIST, cumulative interceptive supportive therapy; FU, follow-up; MBL, marginal (radiographic) bone
loss; Mos, months; NR, not reported; PCP, periodontally compromised patients; PHP, periodontally healthy patients; PIPD, peri-implant probing depth;
Priv., private; Pts/pts, patients; Univ., university; X-ray, radiographic.

Annualized mean PIPD
Similarly to MBL, the annualized mean PIPD (total PIPD/follow-up
duration in years) was analyzed. The annualized PIPD rates still
showed a greater, but not statistically significant, value of WMD in
the test group (PCP) compared to the control group (PHP) (0.03 mm;
95% CI: 0.06–0.12; p = 0.485) (Figure 11A). Furthermore, the het-
erogeneity was still high (I = 89.3%), indicating that the different
2
lengths of observation periods in the studies are not the cause for the
observed differences (Figure 11B). No significant signals of publication
bias were detected by the funnel plot (p = 0.106) (Figure 11C). It is
already known from the total PIPD analysis that the RIS was not
reached (Figure 10D). Since the RIS was not reached with all five
available studies combined, and any subanalyses or stratifications
would further diminish the statistical power, no further analyses were
conducted.
4 | DISCUSSION
deeper into the body of literature to attempt to draw more robust
conclusions. Notably, our meta-analyses that included only prospec-
tive cohort studies revealed a significantly stronger correlation
between having a history of periodontitis and both risk of implant fail-
ure and incidence of peri-implantitis compared to having no history of
periodontitis. Analyses stratified by the three study durations of ≤5,
>5, and exactly 10 years, respectively, consistently demonstrated a
significantly elevated risk of implant failure among PCPs compared to
PHPs across all study durations. In terms of the incidence of peri-
implantitis, meta-analytic results encompassing all studies revealed a
4-fold—and those specifically with 10 years of follow-up an 8.5-fold—
greater rate for PCPs compared to PHPs, respectively.
Additionally, calculations for the mean MBL, both overall and
annualized, indicated a statistically greater bone loss in PCPs, although
with substantial variability between studies and low robustness of the
meta-analytic results as indicated by the TSA. In contrast, comparable
values for the PIPD parameter between the two groups were found,
both overall and annualized.

4.1 | Summary of main findings

The two main goals of our systematic review, meta-analysis, and TSA
were to qualitatively and quantitatively assess and synthesize the cer-
tainty/quality of the evidence from prospective cohort studies regard-
ing associations and potential causality between a history of
periodontitis at the time of implant placement and incidence
of implant failure and peri-implantitis, respectively.
While there is ample evidence on this subject, the methodological
limitations we identified in previous studies prompted us to delve
4.2 | Certainty/quality of the evidence
According to the NOS scoring, 75% (8/12) of the studies were of
‘Good’ quality and the same eight studies had ‘Low’ risk of bias,
whereas the remaining four studies were or ‘Poor’ quality and had
‘High; risk of bias (Table 4). The reason for the latter four studies’
score of ‘Poor’ quality was due to all of them scoring 0 (zero) stars in
the Comparability domain and one study scoring only two of three
possible stars in the Selection domain.
17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
17

Legend on next page.

SERRONI ET AL.

FIGURE 6
 17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
18 SERRONI ET AL.

When applying the GRADE tool for assessment of the certainty/
quality of the evidence relating to the outcomes of interest, the lack
of RCTs automatically imposed an initial rating score of “Low” for
each parameter. In particular, the certainty/quality of the evidence for
implant failure and peri-implantitis incidence was scored as “Low” and
“Very low”, respectively. Despite no significant anomalies surfacing
across the analyzed factors, the absence of upgrading elements pre-
cluded the strengthening of the level of certainty/quality. Concerning
both the overall and annual MBL and PIPD, the certainty/quality of
the evidence was rated “Very low” by the GRADE scoring system.
For the peri-implantitis incidence outcome, the rating of “Serious”
risk of bias stems above all from the indirectness domain, considering
the inhomogeneity among the criteria used to clinically determine the
presence of peri-implantitis. Imprecision, based on the width of
the 95% CI as well as the sample size, proved to be “considerable” for
peri-implantitis incidence and “moderate” for both MBL and PIPD,
whereas high heterogeneity mostly due to the I2 value in the inconsis-
tency domain, the incidence of peri-implantitis parameter was deter-
mined to have “moderate” risk of bias while the MBL and PIPD were
of “Serious” risk of bias.
4.3 | Agreements and disagreements with other
studies
First, this systematic review investigated whether a history of peri-
odontitis might increase the risk of implant failure (Outcome #1) and
found significantly greater risks for the PCP group compared to the
PHP group of 65% and 136% for study durations of ≤5 and >5 years,
respectively. Two prior meta-analyses used eligibility criteria similar to
33,34
ours, but included only two (older) prospective studies. They
reported partially different results regarding implant-level survival/
failure rate. Karoussis and team found no statistically significant dif-
ferences between PHP and PCP in survival rates, neither in the short
nor long-term.33 On the other hand, Sgolastra et al. reported a RR of
1.89 for implant failure, similar to our meta-analysis results showing
the PCP group to have a 1.74 times greater risk than the PHP group.34
Upon evaluating other meta-analyses that manifested notable eligibil-
ity disparities vis-à-vis ours, a series of contradictory results emerged.
73 74
Studies by both Schou et al. and Ramanauskaite et al. failed to
delineate statistically significant differences in implant loss rate
between PHP and PCP groups, both within a <5-year follow-up
period or within a longer term context. In contrast, Carra et al.
reported an RR of 1.81 for implant failure for the PCP group
compared to PHP,31 which result strikingly aligns with the results of
our meta-analysis, despite being based on studies of varying designs
that included only six prospective cohort studies.
Second, this systematic review explored whether a history of
periodontitis might increase the incidence of peri-implantitis (Outcome
#2), and found a significantly almost 4-fold greater risk for the PCP
group compared to the PHP group. Several prior systematic reviews
with meta-analyses also confirmed this hypothesis,31,34,74 but
reported lower odds ratio values than our meta-analysis. The out-
comes of our study are more in line with the meta-analysis by Ferreira
et al.32 who found an OR value of 5.15 when analyzing only cohort
studies. Although the magnitude of the effect in our review is
relevant, the TSA conducted for the incidence of peri-implantitis
established that the results of our meta-analysis are highly probable,
but still inconclusive. These findings diverge from the assertions of
the 2017 World Workshop of the European Federation of Periodon-
tology/American Academy of Periodontology. The workshop posited
that, despite not exclusively relying on longitudinal studies, robust evi-
dence exists supporting the notion that a history of chronic periodon-
titis serves as a significant risk factor or indicator for the development
of peri-implantitis.36
Including studies of various designs, one meta-analysis detected a
significantly greater peri-implantitis incidence only in the long term.33
However, this distinction was not possible in our study since only one
of the five (exclusively prospective cohort) studies investigating this
parameter had a follow-up duration of <5 years.
In agreement with the studies by Lin et al.75 and Sgolastra et al.,34
results of our meta-analysis would seem to suggest that the absence
of a history of periodontitis may also have a protective effect on the
progression of MBL (Outcome #3). Indeed, the PCP group experienced
a significantly more pronounced WDM for the MBL than the PHP
group. However, only six studies provided information on this param-
eter in our meta-analysis. The high heterogeneity—probably related to
outliers by Gatti et al.57 and Mengel et al.61—and the TSA results,
however, undermined the strength of our conclusions.
Finally, regarding the PIPD parameter (Outcome #4), the results of
our meta-analysis did not show any difference between implants
placed in the PHP group and in the PCP group. In disagreement with
our study, Karoussis et al.33 reported a significant long-term increase
in PIPD values in patients with a history of periodontitis. The small
number of eligible studies included, the high heterogeneity, and the
failure to achieve RIS in the TSA could explain this discrepancy. More-
over, it is difficult to compare PIPD in different studies and its values
should always be interpreted with caution. In fact, the PIPD

F I G U R E 6 Incident peri-implantitis rate (n = 5 studies; n = 326 pts; n = 371 PHP + 513 PCP = 884 implants at last visit). (A) Meta-analysis
of LogRR for failure rate. Log RR >0 (equivalent to RR >1) suggests that the failure rate was greater in the PCP group than in the PHP group.
(B) Galbraith plot of inter-study consistency shows moderate consistency (I2 = 52.8%) (moderate level of heterogeneity) between studies.
(C) Funnel plot of LogRR for potential publication bias shows no significant level of asymmetry (p = 0.569, Egger's test) indicating no evidence of
publication bias risk. (D) TSA evaluating the implant failure rates comparing PCP and PHP. The RIS of 1726 implants was not reached.
Abbreviations: CI, confidence interval; EC, events (peri-implantitis) in the control group (PHP); ET, events (peri-implantitis) in the test group (PCP);
PCP, periodontally compromised patients; PHP, periodontally healthy patients; pts, patients; RIS, required information size; TSA, trial sequential
analysis; TT, total number of implants in the test group (PCP); TC, total number of implants in the control group (PHP).
 17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SERRONI ET AL. 19

F I G U R E 7 Incident peri-implantitis rate at 10 years follow-up (n = 3 studies; n = 326 pts; n = 284 PHP + 274 PCP = 558 implants at last
visit) (A) Meta-analysis of LogRR for failure rate. Log RR >0 (equivalent to RR >1) suggests that the failure rate was greater in the PCP group than
in the PHP group. (B) Galbraith plot of inter-study consistency shows high consistency (I2 = 00.0%) between studies. (C) Funnel plot of LogRR for
potential publication bias shows no significant level of asymmetry (p = 0.747, Egger's test) indicating no evidence of publication bias risk. (D) TSA
evaluating the implant failure rates comparing PCP and PHP. The RIS of 852 implants was not reached.
Abbreviations: CI, confidence interval; EC, events (peri-implantitis) in the control group (PHP); ET, events (peri-implantitis) in the test group (PCP);
PCP, periodontally compromised patients; PHP, periodontally healthy patients; pts, patients; RIS, required information size; TSA, trial sequential
analysis; TT, total number of implants in the test group (PCP); TC, total number of implants in the control group (PHP).
 17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
20 SERRONI ET AL.

F I G U R E 8 Comparison of change in marginal bone level (MBL) in PCP and PHP (n = 6 studies; n = 164 PHP + 139 PCP = 303 patients at
last visit). (A) Meta-analysis of WMD for MBL change. (B) Galbraith plot of inter-study consistency shows (I2 = 92.5%) (high level of
heterogeneity) between studies. (C) Funnel plot of WMD for potential publication bias shows a high level of a symmetry ( p = 0.001, Egger's test)
with high level of publication bias risk. (D) TSA evaluating the WMD of the MBL comparing PCP to PHP. RIS (n = 401 implants) was not reached.
Abbreviations: CI, confidence interval; mC, mean in the control group (PHP); mT, mean in the test group (PCP); PCP, periodontally compromised
patients; PHP, periodontally healthy patients; sdC, standard deviation in the control group (PHP); TT, total number of patients in the test group
(PCP); TC, total number of patients in the control group (PHP) WMD, weighted mean difference.
 17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SERRONI ET AL. 21

F I G U R E 9 Comparison of change in annualized marginal bone level (MBL) in PCP and PHP in the same studies as in Figure 8 (n = 6 studies;
n = 164 PHP + 139 PCP = 303 patients at last visit). (A) Meta-analysis of WMD for annualized MBL change. (B) Galbraith plot of inter-study
consistency shows (I2 = 92.5%) (high level of heterogeneity) between studies. (C) Funnel plot of WMD for potential publication bias shows a high
level of a symmetry ( p = 0. 0.149, Egger's test) with high level of publication bias risk.
Abbreviations: CI, confidence interval; mC, mean in the control group (PHP); mT, mean in the test group (PCP); PCP, periodontally compromised
patients; PHP, periodontally healthy patients; sdC, standard deviation in the control group (PHP); TT, total number of patients in the test group
(PCP); TC, total number of patients in the control group (PHP); WMD, weighted mean difference.

measurements around implants could be strongly conditioned by sev-
eral factors, such as the emergence profile of the prosthesis, the posi-
tion of the implant, and the gingival thickness.76
Some systematic reviews of prospective cohort studies also
included studies without a control group that was not exposed to the
risk factor we are investigating. Other systematic reviews and meta-
analyses, however, included retrospective, cross-sectional, and case-
series studies in addition to prospective cohort studies. Therefore, the
methodological differences between our systematic review and prior
meta-analyses on the same topic basically prevent any meaningful
comparison.
Finally, no previous review of the topic has used the novel
method TSA to assess the conclusiveness of the results of the meta-
analyses, NOS for evaluation of the quality and risk of bias of each
study, as well as GRADE assessment for complete evaluation of the
strength/certainty of evidence overall.
17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SERRONI ET AL.

Legend on next page.

FIGURE 10
22
 17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SERRONI ET AL. 23

F I G U R E 1 1 Comparison of annualized mean PIPD among PCP and PHP (n = 5 studies; n = 138 PHP + 152 PCP = 290 patients). (A) Meta-
analysis comparing annualized WMD for PIPD in PCP versus PHP, showing a greater value in the PCP than the PHP group. (B) The Galbraith plot
of inter-study consistency shows a high (I2 = 89.3%) level of heterogeneity. (C) Funnel plot of OR for potential publication bias shows no
significant level of asymmetry ( p = 0.398, Egger's test) indicating no evidence of publication bias risk.
Abbreviations: CI, confidence interval; EC, events (peri-implantitis) in the control group (PHP); ET, events (peri-implantitis) in the test group (PCP);
PCP, periodontally compromised patients; PHP, periodontally healthy patients; pts, patients; RIS, required information size; TT, total number of
patients in the test group (PCP); TC, total number of patients in the control group (PHP).

F I G U R E 1 0 Comparison of mean PIPD among PCP and PHP (n = 5 studies; n = 138 PHP + 152 PCP = 290 patients). (A) Meta-analysis
comparing WMD for PIPD in PCP versus PHP, showing a greater value in the PCP than the PHP group. (B) The Galbraith plot of inter-study
consistency shows a high (I2 = 89.8%) level of heterogeneity. (C) Funnel plot of OR for potential publication bias shows no significant level of
asymmetry (p = 0.398, Egger's test) indicating no evidence of publication bias risk. (D) TSA evaluating the WMD of the PIPD comparing PCP to
PHP. The RIS of 1444 was not reached.
Abbreviations: CI, confidence interval; EC, events (peri-implantitis) in the control group (PHP); ET, events (peri-implantitis) in the test group (PCP);
PCP, periodontally compromised patients; PHP, periodontally healthy patients; pts, patients; RIS, required information size; TSA, trial sequential
analysis; TT, total number of patients in the test group (PCP); TC, total number of patients in the control group (PHP).

24
4.4 | Strengths and limitations
4.4.1 | Strengths
Because of the questions posed, it is not possible to design RCTs,
so by including only prospective longitudinal studies, we explore
the evidence of the best possible design. The TSA evaluation of
the meta-analytic results is novel and generates greater confidence
in the results. Application of the NOS tool provides good assess-
ment of the quality and risk of bias, respectively, by each study.
For completeness' sake, we also applied the commonly used
GRADE system to evaluate the evidence, but due to this tool's reli-
ance on RCTs, it was not very helpful in evaluating the certainty of
the evidence.
4.4.2 | Limitations
Our study suffers from limitations primarily due to confounders
potentially influencing the true relationship between the exposure to
and impact of the putative risk factor. Key confounding variables
encompass smoking habits and variations in implant characteristics as
well as periodontitis case definitions and severity. Other relevant fac-
tors include differences in implant positions, the nature of prosthetic
restoration, timing of implant insertion, the application of guided bone
regeneration procedures; and oral hygiene status. As is the case with
periodontitis, smoking might impact implant survival rates. However,
current literature provides only limited or inconclusive evidence
regarding the association between smoking and peri-implantitis.34,36
Nine of the 12 cohorts in our meta-analyses included cigarette
smokers, with a prevalence ranging from 11.4% to 28.8%. Only two
studies excluded smoking patients via their eligibility criteria.62,63 On
the other hand, one study did not clearly report information about
smoking habits,61 while one study excluded only patients who smoked
58
>10 cigarettes a day. Because no study provided any estimate of
any clustering effect due to multiple implants or several periodontitis
affected teeth being present within the same individual, we had no
way of adjusting for such clustering. Moreover, the available studies
did not report their findings in sufficient detail for us to estimate the
actual MBL and PIPD for each follow-up year. Therefore, our annual-
ized mean values are simply crude means of the total, cumulative
change over the duration of the study divided by the number of years
of follow-up, hence resulting in values that automatically infer the
same rate of change in each of these years, which may not be correct.
Nonetheless, this estimation was necessary to compare results from
the studies with different durations.
The lack of detail in the data reported by the included studies and
the consequent impossibility of conducting a meta-regression analysis
while controlling for such potential confounders must however be
included in the evaluation of our conclusions. Lack of the possibility
to analyze the results according to specific case definitions of peri-
odontitis represents another inherent limitation of our study. How-
ever, due to the 2017 classification of periodontal diseases,77 and the
17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SERRONI ET AL.
conclusions of a recent study conducted by our group that did not
detect any significantly greater incidence of peri-implantitis in patients
with periodontitis Stages III-IV compared with Stages I and II,39 we
did not consider it appropriate to make any subdivisions by periodon-
titis case definition.
A significant limitation of our study arises from the application of
by now outdated periodontitis case definitions as well as the absence
of uniformity in peri-implantitis diagnostic criteria and consequently
case definitions. Since all cohorts were recruited before 2014, none
adhered to the diagnostic guidelines for peri-implantitis established by
the 2017 world workshop.36 This lack of consistency resulted in
imprecision and unreliability in our analyses.
Consequently, we welcome the publication of the international
consensus report named “Relevant domains, core outcome sets and
measurements for implant dentistry clinical trials: The Implant Dentistry
Core Outcome Set and Measurement (ID-COSM).”78 We hope that
future researchers will follow these recommendations for both study
design and reporting of results and thereby facilitate comparisons of
results from different studies regarding implants and hence promote
greater certainty/quality of future evidence.
5 | CONC LU SION
Within the limitations of this study that could not adjust for potential
confounders, the evidence derived from the available prospective
cohort studies demonstrated that a history of periodontitis is a risk
factor for implant failure and peri-implantitis. PCPs were statistically
significantly associated with 74% increased odds of implant failure
both overall, and by 62% after shorter (≤5 years) and 126% after lon-
ger (>5 years) study durations, respectively. In addition, the risk of
developing peri-implantitis was found to be 4-fold greater in PCPs
compared to PHPs. The magnitude of MBL is also greater in PCP
patients, but not conclusively, while no difference with PHP patients
was detected for PIPD.
AUTHOR CONTRIBU TIONS
Andrea Ravidà and Matteo Serroni conceived the concept/design.
Matteo Serroni and Giuseppe Balice conducted the data collection.
Matteo Serroni, Andrea Ravidà, Wenche S. Borgnakke, Michele Pao-
lantonio, Luigi Romano, and Muhammad H. A Saleh were involved in
the analysis/interpretation of the data. Matteo Serroni, Wenche
S. Borgnakke, and Andrea Ravidà drafted the article. All the authors
critically revised the manuscript. Luigi Romano, Matteo Serroni,
Andrea Ravidà, and Giuseppe Balice secured funding for the statisti-
cian who conducted the analyses. All authors approved the final
manuscript.
ACKNOWLEDG MENT
None.
CONFLIC T OF INTER E ST STATEMENT
The authors declare no conflict of interest.

SERRONI ET AL.
DATA AVAI LAB ILITY S TATEMENT
All the data that supports the findings of this study are available in the
cited publications. No new data were generated for this study.
ORCID
Matteo Serroni https://orcid.org/0000-0002-2081-6651
Wenche S. Borgnakke https://orcid.org/0000-0003-3593-093X
Michele Paolantonio https://orcid.org/0000-0002-6139-6665
Muhammad H. A. Saleh https://orcid.org/0000-0001-5067-7317
Andrea Ravidà https://orcid.org/0000-0002-3029-8130
RE FE R ENC E S
1. Moraschini V, Poubel LA, Ferreira VF, Barboza ES. Evaluation of sur-
vival and success rates of dental implants reported in longitudinal
studies with a follow-up period of at least 10 years: a systematic
review. Int J Oral Maxillofac Surg. 2015;44(3):377-388. doi:10.1016/j.
ijom.2014.10.023
2. Tomasi C, Albouy JP, Schaller D, Navarro RC, Derks J. Efficacy of
rehabilitation of stage IV periodontitis patients with full-arch fixed
prostheses: tooth-supported versus implant-supported: a systematic
review. J Clin Periodontol. 2022;49(Suppl 24):248-271. doi:10.1111/
jcpe.13511
3. Renvert S, Persson GR, Pirih FQ, Camargo PM. Peri-implant health,
peri-implant mucositis, and peri-implantitis: case definitions and diag-
nostic considerations. J Clin Periodontol. 2018;45(Suppl 20):S278-
S285. doi:10.1111/jcpe.12956
4. Iusan SAL, Lucaciu OP, Petrescu NB, et al. The main bacterial commu-
nities identified in the sites affected by periimplantitis: a systematic
review. Microorganisms. 2022;10(6):1232. doi:10.3390/
microorganisms10061232

5. Carvalho EBS, Romandini M, Sadilina S, Sant'Ana ACP, Sanz M. Micro-
biota associated with peri-implantitis - a systematic review with
meta-analyses. Clin Oral Implants Res. 2023;34(11):1176-1187. doi:
10.1111/clr.14153
6. Retamal-Valdes B, Formiga MC, Almeida ML, et al. Does subgingival
bacterial colonization differ between implants and teeth? A system-
atic review. Braz Oral Res. 2019;33(Suppl 1):e064. doi:10.1590/1807-
3107bor-2019.vol33.0064
7. Gazil V, Bandiaky ON, Renard E, Idiri K, Struillou X, Soueidan A. Cur-
rent data on oral peri-implant and periodontal microbiota and its path-
ological changes: a systematic review. Microorganisms. 2022;10(12):
2466. doi:10.3390/microorganisms10122466
8. Rajasekar A, Varghese SS. Microbiological profile in periodontitis and
peri-implantitis: a systematic review. J Long Term Eff Med Implants. 2022;
32(4):83-94. doi:10.1615/JLongTermEffMedImplants.2022043121
9. Zhou N, Huang H, Liu H, et al. Microbiota analysis of peri-implant
mucositis in patients with periodontitis history. Clin Oral Investig.
2022;26(10):6223-6233. doi:10.1007/s00784-022-04571-1
10. Kim HJ, Ahn DH, Yu Y, et al. Microbial profiling of peri-implantitis
compared to the periodontal microbiota in health and disease using
16S rRNA sequencing. J Periodontal Implant Sci. 2023;53(1):69-84.
doi:10.5051/jpis.2202080104
11. Renvert S, Quirynen M. Risk indicators for peri-implantitis; a narrative
review. Clin Oral Implants Res. 2015;26(Suppl 11):15-44. doi:10.
1111/clr.12636
12. D'Ambrosio F. Periodontal and peri-implant diagnosis: current evi-
dence and future directions. Diagnostics. 2024;14(3):256. doi:10.
3390/diagnostics14030256
13. Guabello G, Zuffetti F, Ravidà A, et al. Avoiding implant-related com-
plications in medically compromised patients with or without
unhealthy lifestyle/elevated oxidative stress. Periodontol 2000. 2023;
92(1):329-349. doi:10.1111/prd.12503
17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
25
14. Pjetursson BE, Helbling C, Weber HP, et al. Peri-implantitis suscepti-
bility as it relates to periodontal therapy and supportive care. Clin Oral
Implants Res. 2012;23(7):888-894. doi:10.1111/j.1600-0501.2012.
02474.x
15. Monje A, Kan JY, Borgnakke W. Impact of local
predisposing/precipitating factors and systemic drivers on peri-
implant diseases. Clin Implant Dent Relat Res. 2023;25(4):640-660.
doi:10.1111/cid.13155
16. Kotsakis GA, Romanos GE. Biological mechanisms underlying compli-
cations related to implant site preparation. Periodontol 2000. 2022;
88(1):52-63. doi:10.1111/prd.12410
17. Belibasakis GN. Microbiological and immuno-pathological aspects of
peri-implant diseases. Arch Oral Biol. 2014;59(1):66-72. doi:10.1016/
j.archoralbio.2013.09.013
18. Berglundh T, Jepsen S, Stadlinger B, Terheyden H. Peri-implantitis
and its prevention. Clin Oral Implants Res. 2019;30(2):150-155. doi:
10.1111/clr.13401
19. Darby I. Risk factors for periodontitis & peri-implantitis. Periodontol
2000. 2022;90(1):9-12. doi:10.1111/prd.12447
20. Genco RJ, Borgnakke WS. Risk factors for periodontal disease. Period-
ontol 2000. 2013;62(1):59-94. doi:10.1111/j.1600-0757.2012.
00457.x
21. Monje A, Catena A, Borgnakke WS. Association between diabetes
mellitus/ hyperglycaemia and peri-implant diseases: systematic
review and meta-analysis. J Clin Periodontol. 2017;44(6):636-648. doi:
10.1111/jcpe.12724
22. Tan J, Lamont GJ, Scott DA. Tobacco-enhanced biofilm formation by
Porphyromonas gingivalis and other oral microbes. Mol Oral Microbiol.
2024. doi:10.1111/omi.12450
23. Chih SM, Cheng CD, Chen SH, Sung CE, Huang RY, Cheng WC. The
impact of smoking on peri-implant microbiota: a systematic review.
J Dent. 2023;133:104525. doi:10.1016/j.jdent.2023.104525
24. Naseri R, Yaghini J, Feizi A. Levels of smoking and dental implants fail-
ure: a systematic review and meta-analysis. J Clin Periodontol. 2020;
47(4):518-528. doi:10.1111/jcpe.13257
25. Shi LX, Zhang L, Zhang DL, et al. Association between TNF-alpha
G-308A (rs1800629) polymorphism and susceptibility to chronic peri-
odontitis and type 2 diabetes mellitus: a meta-analysis. J Periodontal
Res. 2021;56(2):226-235. doi:10.1111/jre.12820
26. Tegelberg P, Leppilahti JM, Ylöstalo A, et al. Genome-wide associa-
tion study of periodontal pocketing in Finnish adults. BMC Oral
Health. 2021;21(1):611. doi:10.1186/s12903-021-01964-8
27. Jin Q, Teng F, Cheng Z. Association between common polymorphisms
in IL-1 and TNFalpha and risk of peri-implant disease: a meta-analysis.
PLoS One. 2021;16(10):e0258138. doi:10.1371/journal.pone.
0258138
28. Ibáñez L, de Mendoza I, Setien-Olarra A, García-De la Fuente AM,
Aguirre-Urizar JM, Marichalar-Mendia X. Role of proinflammatory
mutations in peri-implantitis: systematic review and meta-analysis. Int
J Implant Dent. 2022;8(1):2. doi:10.1186/s40729-022-00400-y
29. Alves CH, Russi KL, Rocha NC, et al. Host-microbiome interactions
regarding peri-implantitis and dental implant loss. J Transl Med. 2022;
20(1):425. doi:10.1186/s12967-022-03636-9
30. Anitua E, Alkhraisat MH, Eguia A. On peri-implant bone loss theories:
trying to piece together the jigsaw. Cureus. 2023;15(1):e33237. doi:
10.7759/cureus.33237
31. Carra MC, Rangé H, Swerts PJ, Tuand K, Vandamme K, Bouchard P.
Effectiveness of implant-supported fixed partial denture in patients
with history of periodontitis: a systematic review and meta-analysis.
J Clin Periodontol. 2022;49(Suppl 24):208-223. doi:10.1111/jcpe.
13481
32. Ferreira SD, Martins CC, Amaral SA, et al. Periodontitis as a risk fac-
tor for peri-implantitis: systematic review and meta-analysis of
observational studies. J Dent. 2018;79:1-10. doi:10.1016/j.jdent.
2018.09.010

26
33. Karoussis IK, Kotsovilis S, Fourmousis I. A comprehensive and critical
review of dental implant prognosis in periodontally compromised par-
tially edentulous patients. Clin Oral Implants Res. 2007;18(6):669-679.
doi:10.1111/j.1600-0501.2007.01406.x
34. Sgolastra F, Petrucci A, Severino M, Gatto R, Monaco A. Periodontitis,
implant loss and peri-implantitis; a meta-analysis. Clin Oral Implants
Res. 2015;26(4):e8-e16. doi:10.1111/clr.12319
35. Stacchi C, Berton F, Perinetti G, et al. Risk factors for peri-implantitis:
effect of history of periodontal disease and smoking habits. A system-
atic review and meta-analysis. J Oral Maxillofac Res. 2016;7(3):e3. doi:
10.5037/jomr.2016.7303
36. Schwarz F, Derks J, Monje A, Wang HL. Peri-implantitis. J Clin Period-
ontol. 2018;45(Suppl 20):S246-S266. doi:10.1111/jcpe.12954
37. Astolfi V, Ríos-Carrasco B, Gil-Mur FJ, et al. Incidence of peri-
implantitis and relationship with different conditions: a retrospective
study. Int J Environ Res Public Health. 2022;19(7):4147. doi:10.3390/
ijerph19074147
38. Seki K, Hasuike A, Hagiwara Y. Clinical evaluation of the relationship
between systemic disease and the time of onset of peri-implantitis: a
retrospective cohort study. J Oral Implantol. 2023;49(1):55-61. doi:
10.1563/aaid-joi-D-21-00186
39. Ravidà A, Rodriguez MV, Saleh MHA, et al. The correlation between
history of periodontitis according to staging and grading and the
prevalence/severity of peri-implantitis in patients enrolled in mainte-
nance therapy. J Periodontol. 2021;92(11):1522-1535. doi:10.1002/
JPER.21-0012
40. Heitz-Mayfield LJ, Aaboe M, Araujo M, et al. Group 4 ITI consensus
report: risks and biologic complications associated with implant den-
tistry. Clin Oral Implants Res. 2018;29(Suppl 16):S351-S358. doi:10.
1111/clr.13307
41. Heitz-Mayfield LJA, Salvi GE, Mombelli A, et al. Supportive peri-
implant therapy following anti-infective surgical peri-implantitis treat-
ment: 5-year survival and success. Clin Oral Implants Res. 2018;29(1):
1-6. doi:10.1111/clr.12910
42. Heitz-Mayfield LJA, Heitz F, Lang NP. Implant disease risk assessment
IDRA-a tool for preventing peri-implant disease. Clin Oral Implants
Res. 2020;31(4):397-403. doi:10.1111/clr.13585
43. Borrell LN, Papapanou PN. Analytical epidemiology of periodontitis.
J Clin Periodontol. 2005;32(Suppl 6):132-158. doi:10.1111/j.1600-
051X.2005.00799.x
44. Heitz-Mayfield LJ. Peri-implant diseases: diagnosis and risk indicators.
J Clin Periodontol. 2008;35(8 Suppl):292-304. doi:10.1111/j.1600-
051X.2008.01275.x
45. Kang H. Trial sequential analysis: novel approach for meta-analysis.
Anesth Pain Med (Seoul). 2021;16(2):138-150. doi:10.17085/apm.
21038
46. Wells GA, Shea B, O'Connell D, et al. The Newcastle-Ottawa scale
(NOS) for assessing the quality of nonrandomised studies in meta-
analyses. 2011 http://www.ohri.ca/programs/clinical_epidemiology/
oxford.asp
47. Guyatt G, Oxman AD, Akl EA, et al. GRADE guidelines: 1. Introduc-
tion—GRADE evidence profiles and summary of findings tables. J Clin
Epidemiol. 2011;64(4):383-394. doi:10.1016/j.jclinepi.2010.04.026
48. Morgan RL, Whaley P, Thayer KA, Schünemann HJ. Identifying the
PECO: a framework for formulating good questions to explore
the association of environmental and other exposures with health
outcomes. Environ Int. 2018;121(Pt 1):1027-1031. doi:10.1016/j.
envint.2018.07.015
49. Schünemann H, Brożek J, Guyatt G, Oxman A, eds. GRADE Hand-
book 2013. 2013 https://gdt.gradepro.org/app/handbook/handbook.
html
50. Baumeister SE, Schlecht I, Trabert B, Nolde M, Meisinger C,
Leitzmann MF. Anthropometric risk factors for ovarian cancer in the
NIH-AARP diet and health study. Cancer Causes Control. 2021;32(3):
231-239. doi:10.1007/s10552-020-01377-y
17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
SERRONI ET AL.
51. Higgins JPT, Thomas JSE, Chandler J, et al. Cochrane Handbook for
Systematic Reviews of Interventions Version 6.0 (Updated July 2019).
2nd ed. John Wiley & Sons; 2019.
52. Armitage GC. Development of a classification system for periodontal
diseases and conditions. Ann Periodontol. 1999;4(1):1-6. doi:10.1902/
annals.1999.4.1.1
53. Page RC, Kornman KS. The pathogenesis of human periodontitis: an
introduction. Periodontol 2000. 1997;14:9-11. doi:10.1111/j.1600-
0757.1997.tb00189.x
54. R Core Team. R: a language and environment for statistical comput-
ing. R Foundation for Statistical Computing, Vienna. 2018 https://
www.R-project.org
55. de Boever AL, Quirynen M, Coucke W, Theuniers G, de Boever JA.
Clinical and radiographic study of implant treatment outcome in peri-
odontally susceptible and non-susceptible patients: a prospective
long-term study. Clin Oral Implants Res. 2009;20(12):1341-1350. doi:
10.1111/j.1600-0501.2009.01750.x
56. Degidi M, Nardi D, Piattelli A. 10-year prospective cohort follow-up
of immediately restored XiVE implants. Clin Oral Implants Res. 2016;
27(6):694-700. doi:10.1111/clr.12642
57. Gatti C, Gatti F, Chiapasco M, Esposito M. Outcome of dental
implants in partially edentulous patients with and without a history of
periodontitis: a 5-year interim analysis of a cohort study. Eur J Oral
Implantol. 2008;1(1):45-51.
58. Jiang BQ, Lan J, Huang HY, et al. A clinical study on the effectiveness
of implant supported dental restoration in patients with chronic peri-
odontal diseases. Int J Oral Maxillofac Surg. 2013;42(2):256-259. doi:
10.1016/j.ijom.2012.08.001
59. Karoussis IK, Salvi GE, Heitz-Mayfield LJ, Bragger U, Hammerle CH,
Lang NP. Long-term implant prognosis in patients with and without a
history of chronic periodontitis: a 10-year prospective cohort study
of the iti dental implant system. Clin Oral Implants Res. 2003;14(3):
329-339. doi:10.1034/j.1600-0501.000.00934.x
60. Levin L, Ofec R, Grossmann Y, Anner R. Periodontal disease as a risk
for dental implant failure over time: a long-term historical cohort
study. J Clin Periodontol. 2011;38(8):732-737. doi:10.1111/j.1600-
051X.2011.01745.x
61. Mengel R, Behle M, Flores-de-Jacoby L. Osseointegrated implants in
subjects treated for generalized aggressive periodontitis: 10-year
results of a prospective, long-term cohort study. J Periodontol. 2007b;
78(12):2229-2237. doi:10.1902/jop.2007.070201
62. Mengel R, Flores-de-Jacoby L. Implants in patients treated for gener-
alized aggressive and chronic periodontitis: a 3-year prospective lon-
gitudinal study. J Periodontol. 2005;76(4):534-543. doi:10.1902/jop.
2005.76.4.534
63. Mengel R, Kreuzer G, Lehmann KM, Flores-de-Jacoby L. A telescopic
crown concept for the restoration of partially edentulous patients
with aggressive generalized periodontitis: a 3-year prospective longi-
tudinal study. Int J Periodontics Restorative Dent. 2007a;27(3):
231-239.
64. Roccuzzo A, Imber JC, Marruganti C, Salvi GE, Ramieri G,
Roccuzzo M. Clinical outcomes of dental implants in patients with
and without history of periodontitis: a 20-year prospective study.
J Clin Periodontol. 2022;49(12):1346-1356. doi:10.1111/jcpe.13716
65. Roccuzzo M, Bonino F, Aglietta M, Dalmasso P. Ten-year results of a
three arms prospective cohort study on implants in periodontally
compromised patients. Part 2: clinical results. Clin Oral Implants Res.
2012;23(4):389-395. doi:10.1111/j.1600-0501.2011.02309.x
66. Roccuzzo M, Bonino L, Dalmasso P, Aglietta M. Long-term results of
a three arms prospective cohort study on implants in periodontally
compromised patients: 10-year data around sandblasted and acid-
etched (SLA) surface. Clin Oral Implants Res. 2014;25(10):1105-1112.
doi:10.1111/clr.12227
67. Roccuzzo M, de Angelis N, Bonino L, Aglietta M. Ten-year results of a
three-arm prospective cohort study on implants in periodontally

SERRONI ET AL.
compromised patients. Part 1: implant loss and radiographic bone
loss. Clin Oral Implants Res. 2010;21(5):490-496. doi:10.1111/j.1600-
0501.2009.01886.x
68. Swierkot K, Lottholz P, Flores-de-Jacoby L, Mengel R. Mucositis, peri-
implantitis, implant success, and survival of implants in patients with
treated generalized aggressive periodontitis: 3- to 16-year results of a
prospective long-term cohort study. J Periodontol. 2012;83(10):1213-
1225. doi:10.1902/jop.2012.110603
69. Landry RG, Jean M. Periodontal screening and recording (PSR) index:
precursors, utility and limitations in a clinical setting. Int Dent J. 2002;
52(1):35-40. doi:10.1111/j.1875-595x.2002.tb00595.x
70. Albrektsson T, Isidor F. Consensus report: implant therapy. Proceed-
ings of the 1st European workshop on periodontology, charter house
at Ittingen, Thurgau, Switzerland, February 1–4, 1993. Quintessence,
Berlin, Germany 1994:365–369. 1994.
71. Mombelli A, Lang NP. The diagnosis and treatment of peri-implantitis.
Periodontol 2000. 1998;17:63-76. doi:10.1111/j.1600-0757.1998.
tb00124.x
72. Silness J, Löe H. Periodontal disease in pregnancy. II. Correlation
between oral hygiene and periodontal condition. Acta Odontol Scand.
1964;22(1):121-135. doi:10.3109/00016356408993968
73. Schou S. Implant treatment in periodontitis-susceptible patients: a
systematic review. J Oral Rehabil. 2008;35(Suppl 1):9-22. doi:10.
1111/j.1365-2842.2007.01830.x
74. Ramanauskaite A, Baseviciene N, Wang HL, Tözüm TF. Effect of his-
tory of periodontitis on implant success: meta-analysis and systematic
review. Implant Dent. 2014;23(6):687-696. doi:10.1097/ID.
0000000000000156
75. Lin CY, Chen Z, Pan WL, Wang HL. Is history of periodontal disease still
a negative risk indicator for peri-implant health under supportive post-
17088208, 0, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/cid.13330, Wiley Online Library on [26/05/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
27
implant treatment coverage? A systematic review and meta-analysis. Int
J Oral Maxillofac Implants. 2020;35(1):52-62. doi:10.11607/jomi.7714
76. Serino G, Turri A, Lang NP. Probing at implants with peri-implantitis
and its relation to clinical peri-implant bone loss. Clin Oral Implants
Res. 2013;24(1):91-95. doi:10.1111/j.1600-0501.2012.02470.x
77. Tonetti MS, Greenwell H, Kornman KS. Staging and grading of peri-
odontitis: framework and proposal of a new classification and case
definition. J Clin Periodontol. 2018;45(Suppl 20):S149-S161. doi:10.
1111/jcpe.12945
78. Tonetti MS, Sanz M, Avila-Ortiz G, et al. Relevant domains, core out-
come sets and measurements for implant dentistry clinical trials: the
implant dentistry core outcome set and measurement (ID-COSM)
international consensus report. J Clin Periodontol. 2023;50(Suppl 25):
5-21. doi:10.1111/jcpe.13808
SUPPORTING INF ORMATION
Additional supporting information can be found online in the Support-
ing Information section at the end of this article.
How to cite this article: Serroni M, Borgnakke WS, Romano L,
et al. History of periodontitis as a risk factor for implant failure
and incidence of peri-implantitis: A systematic review, meta-
analysis, and trial sequential analysis of prospective cohort
studies. Clin Implant Dent Relat Res. 2024;1‐27. doi:10.1111/
cid.13330