Accepted Article

DR. ROOHOLLAH NASERI (Orcid ID : 0000-0002-9252-6565)

Article type : Systematic Review

Levels of smoking and dental implants failure: a systematic review and meta-
analysis.

Roohollah Naseri, Dental Research Center, Department of Periodontics, Dental Research Institute, School
of Dentistry, Isfahan University of Medical Science, Isfahan, Iran.
Jaber Yaghini, Dental Implants Research Center, Department of Periodontics, Dental research institute,
School of dentistry, Isfahan University of Medical Sciences, Isfahan, Iran.
Awat Feizi, Department of Epidemiology and Biostatistics, School of Health, Isfahan University of
Medical Sciences, Isfahan, Iran.

Running title: Levels of smoking and dental implant failure

Keywords: Dental implants, Smoking, Implant failure rate, Meta-analysis

Correspondence address:
Jaber Yaghini
Department of Periodontics
School of Dentistry
Isfahan University of Medical Science
Hezar jarib St.
Isfahan, Iran
E-mail: j_yaghini@dnt.mui.ac.ir
Conflict of Interest and Sources of Funding Statement:
The authors declare that there are no conflicts of interest in this study

This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process, which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1111/JCPE.13257
This article is protected by copyright. All rights reserved
Accepted Article
Abstract
Aim: The present systematic review and meta-analysis was performed to investigate if there was a
significantly enhanced risk of dental implant failure due to the increased number of cigarettes
smoked per day.
Materials and Methods:
Four databases, including PubMed, Embase, Web of Science, and Scopus were searched until
January, 2019. The search terms “dental implant, oral implant, smoking, smoker, tobacco,
nicotine, and non-smoker” were used in combination to identify the publications providing data
for dental implant failures related to the smoking habit. Publications were excluded if the quantity
of cigarettes consumed per day was not reported. Fixed- or random-effects meta-analyses were
used to pool the estimates of relative risk (RR) with 95% confidence intervals (CI).
Results:
Having additional information supplied by the authors, 23 articles were selected for final analysis.
The meta‐analyses based on implant- and patient- related data showed a significant increase in the
RR of implant failure in patients who smoked >20 cigarettes per day compared with non-smokers
(Implant based: P = 0.001; RR: 2.45; CI: 1.42-4.22 and Patient based: P < 0.001; RR: 4; CI: 2.72-
5.89).
Conclusion: The risk of implant failure was elevated with an increase in the number of cigarettes
smoked per day.

Clinical Relevance

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 Scientific rationale for study: Recent meta-analyses have reported a higher risk of dental implant
Accepted Article
failure in smokers, but the association between the number of cigarettes smoked and implant
failure is still unknown.
Principal findings: The findings showed the more cigarettes smoked daily, the more was the
probability of dental implant failure.
Practical implications: It seems that implant failure due to cigarette smoking operates along a
continuum. Smoking more than one pack/day can be considered a risk factor for implant failure.

Introduction:
Today's dental implants are highly successful (Levin, Laviv, & Schwartz‐Arad, 2006;
Schwartz‐Arad, Herzberg, & Levin, 2005). However, some factors might make patients
susceptible to a greater risk for implant failure. A better understanding of the factors associated
with the failure of implants provides an insight into predicting the dental implant outcomes.
Clinical studies have introduced several risk factors that may affect the short- and long-term
implant success, including quality and volume of bone, jaw location, implant dimensions, and
augmentation procedures, as well as systemic and environmental conditions, such as diabetes
mellitus and smoking (Bornstein, Cionca, & Mombelli, 2009; Palma-Carrió, Maestre-Ferrín,
Peñarrocha-Oltra, Peñarrocha-Diago, & Peñarrocha-Diago, 2011).
Previous studies have proved the detrimental effects of smoking on oral health. Oral precancerous
lesions, oral cancers and periodontal diseases are some of its effects on the oral cavity (Calsina,
Ramón, & Echeverría, 2002; Johnson & Bain, 2000). Smokers also have a higher rate of tooth loss
than non-smokers and the demands for dental implants in smoking patients have gradually been
increased (Jansson & Lavstedt, 2002). Some recent meta-analyses have reported a higher risk of
dental implant failure in smokers (Chen, Liu, Xu, Qu, & Lu, 2013; Chrcanovic, Albrektsson, &
Wennerberg, 2015; Moraschini, 2016; Strietzel et al., 2007). Smoking has also been shown to be a
risk factor for peri-implantitis (Heitz‐Mayfield, 2008; Renvert & Quirynen, 2015). Smokers have
shown a significant increase in the marginal bone loss around implants as compared with non-
smokers (Qian, Wennerberg, & Albrektsson, 2012). Therefore, identification of smoking patients
before implant therapy seems to be necessary. Current patient smoking status is the least
information that should be recorded (number of cigarettes smoked per day). The association
between the number of cigarettes smoked and implant failure is still unknown, but heavy smokers
may show a higher incidence (Alsaadi, Quirynen, Komarek, & van Steenberghe, 2007; Twito &

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 Sade, 2014; van Steenberghe, Facobs, Desnyder, Maffei, & Quirynen, 2002). A new critical
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review addressed this issue but failed to determine a relationship between the quantity of cigarette
consumption (in terms of smoking dose) and its effect on dental implant failure (Barzanji,
Chatzopoulou, & Gillam, 2018). However, this review was only able to include 8 studies
according to their inclusion criteria. In addition, there are some discrepancies in defining the heavy
smokers in various studies. Hence, we performed a systematic review and meta-analysis
concerning the relationship between the quantity of smoking and dental implant failure. This
research sought to determine if there was a significantly enhanced risk of implant failures in heavy
smokers compared with light smokers. Publications have reported the dental implant failure rates
on an implant- and/or patient-related basis. The patient-related data are based on the assumption
that patients are independent from each other, but implants within a patient mouth may be
correlated with each other (Herrmann, Lekholm, & Holm, 2003; Herrmann, Lekholm, Holm, &
Karlsson, 1999). This systematic review provided both implant- and patient-related data for implant
failure in smoker subgroups.
Materials and Methods
The methodology of this study was prepared in accordance to the PRISMA statement (Moher,
Liberati, Tetzlaff, & Altman, 2009). The study has been registered with PROSPERO, number
CRD42019121556. The purpose of the present systematic review and meta-analysis was to assess
the null hypothesis that there would be no difference in the implant failure rates by increasing the
quantity of cigarettes smoked per day. The focused question according to the PICO format
(Patient, Intervention, Comparison, and Outcome) was: in patients undergoing dental implant
placement, are heavy smoker patients versus light smokers at a higher risk for implant failure, on
an implant- and/or patient-related basis?
Search strategy
An electronic search was performed, with no time or language restrictions, in the following
electronic bibliographic databases: PubMed, EMBASE, Web of Science and Scopus, up to
January 2019. The following search model was accomplished using Boolean operators: (‘‘dental
implant’’ OR ‘‘oral implant’’) AND (‘‘smoking’’ OR ‘‘smoker’’ OR ‘‘tobacco’’ OR ‘‘nicotine’’
OR ‘‘non-smoker’’) (See the search strategies based on each database-specific filter in appendix-
supporting information). The reference part of the included studies (cross-referencing) and
previous systematic reviews was also searched for further papers. Smoking has been rarely
considered the main focus in dental implant studies and has been investigated as a complicating

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 factor involved in the implant success. Therefore, a broad-based search strategy was adopted to
Accepted Article
seek the articles that studied the effect of smoking on implant failure.
Selection criteria
A literature search was performed to seek randomized-controlled clinical trials, cohort studies or
case-control studies, and case series. The exclusion criteria were animal studies, in vitro studies,
case reports, finite element analysis studies, and reviews. Articles providing data on dental implant
failures related to the smoking habit were considered eligible in the first analysis. Publications
were excluded if the quantity of cigarettes consumed per day was not reported and smoking status
was not categorized at least in two subgroups (i.e. light smokers vs. heavy smokers). In this article,
implants were considered failures if they fulfilled the failure criteria presented in Table 1
(Table_1_SuppInfo.docx). To calculate the patient-level failure, if one or more implants were
failed in a patient, the treatment outcome was defined as failure.
Study Selection
The titles and abstracts of the searched results were screened initially by two independent authors
(R. N. and J. Y.). Publications were included for full text evaluation if they met the inclusion
criteria in the first analysis, or if insufficient information was provided in the title and abstract to
enable a decision to be made. Following full assessment, studies were either selected for inclusion
or rejected. Any disagreement between the authors was resolved by discussion with a third review
author (A. F.). In the papers that included inadequate or limited information about dental implant
failure in the smoking subgroups, the corresponding authors were contacted via e-mail for
clarification and requesting the missing data, and a reminder e-mail was sent twice after.
Quality Assessment
Quality assessment of the included observational studies was performed using the Newcastle–
Ottawa scale (NOS) (Peterson, Welch, Losos, & Tugwell, 2011). The NOS includes three
categories, and allocates a maximum of nine points, as follows: four points for selection, two
points for comparability and three points for outcome. Articles scoring six points or more were
considered to be of high quality.
Data Extraction
The following data, if available, were extracted from the studies selected for inclusion by one of
the reviewers: year of publication, country, study design, follow-up period, age of the subjects,
number of patients, smoking status, implant system, implant surface modification, dental implant

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 failure definition and failed and placed implants in the smoking subgroups based on implant-
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and/or patient-related data.
Statistical analysis
Because cigarette consumption was presented in different categories in the articles and meta-
analyses were performed separately in each category, for articles with different categories of
smoking, if possible, the odds ratios (ORs) of implant failure were also synthesized into other
smoking classifications to perform the meta-analysis. In cases where no events were observed in
each smoking subgroup, 0.5 was considered the significance value of these subgroups because
calculation of an OR was undefined (Fleiss, Levin, & Paik, 1981). Statistical heterogeneities were
assessed using Cochran’s Q-statistics (Lipsey & Wilson, 2001), the heterogeneity was quantified
using I² statistical test (J. P. Higgins & Thompson, 2002). I² values ranging from 0% to 100%, and
I² values of 25%, 50%, and 75% were indicated low, moderate, and high levels of heterogeneity,
respectively (J. P. Higgins & Thompson, 2002). If a statistically significant (P < 0.05)
heterogeneity was found, a random-effects model was used. A fixed-effect model was applied if
no statistically significant heterogeneity was observed. The funnel plot and Begg’s and Egger’s
tests were used to assess the publication bias. Sensitivity analysis was conducted to explore the
extent to which inferences might depend on a particular study or number of publications.
Statistical analyses were conducted using Stata version 11.2 (Stata Corp, College Station, TX,
USA). P < 0.05 was considered statistically significant.
Results
The flow diagram of the selection process is drawn in Fig. 1. The search strategy yielded 5035
papers, from which 2782 articles remained after elimination of the duplicate records. After
assessment of titles and abstracts, 2280 articles were omitted. Full text evaluation was performed
on the remaining 502 articles. 479 papers were excluded as they did not conform to the inclusion
criteria:
In 397 studies, the number and/or quantity of cigarettes was not reported. 109 studies reported the
quantity of cigarette smoking. Of them, 47 studies had excluded some smoking subgroups (Light
smokers or heavy smokers). Two studies were published with the same patient sample (further
results) (E. F. Gherlone et al., 2015; Enrico F Gherlone et al., 2016). In 41 papers, the
corresponding authors were contacted via e-mail for clarification of the missing data, 11 emails
were not delivered to the corresponding authors because the email addresses were not valid, and
23 authors did not respond to the additional information or could not retrieve the requested data. In

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 one article, information on implant failure in smoker subgroups was extracted from the chart (van
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Steenberghe et al., 2002). Finally, 23 publications, including one clinical trial (Agliardi, Clericò,
Ciancio, & Massironi, 2010), 6 prospective studies (Brizuela, Martín, Fernández, Larrazábal, &
Anta, 2014; Cercadillo-Ibarguren, Sánchez-Torres, Figueiredo, & Valmaseda-Castellón, 2017;
Franceschetti et al., 2014; E. F. Gherlone et al., 2015; Hinze, Thalmair, Bolz, & Wachtel, 2009;
Strietzel & Reichart, 20F07) and 16 retrospective studies (Alsaadi et al., 2007; Alsaadi, Quirynen,
Komarek, & van Steenberghe, 2008; Arora et al., 2017; Balderas Tamez, Neri Zilli, Fandiño, &
Guizar, 2017; Bornstein, Halbritter, Harnisch, Weber, & Buser, 2008; Correia, Gouveia, Felino,
Costa, & Almeida, 2017; Guido Mangano & Ghertasi Oskouei, 2018; Habsha, 2000; Kan,
Rungcharassaeng, Lozada, & Goodacre, 1999; Nitzan, Mamlider, Levin, & Schwartz-Arad, 2005;
Noguerol, Munoz, Mesa, de Dios Luna, & O'Valle, 2006; Peñarrocha, Guarinos, Sanchis, &
Balaguer, 2002; Sanchez-Perez, Moya-Villaescusa, & Caffesse, 2007; Testori, Weinstein,
Taschieri, & Del Fabbro, 2012; Twito & Sade, 2014; van Steenberghe et al., 2002) were included
in this systematic review and meta-analysis (31129 implants).
Detailed characteristics of the 23 included studies are presented in Table 2 (Table_2A and
2B_SuppInfo.docx). In four papers, the patients received implants in areas with sinus lifting
procedures (Brizuela et al., 2014; Franceschetti et al., 2014; Kan et al., 1999; Testori et al., 2012);
three studies reported the results of immediate implant loading (Agliardi et al., 2010; Cercadillo-
Ibarguren et al., 2017; Hinze et al., 2009), one study recruited patients with history of periodontal
disease (Correia et al., 2017), and one paper studied implant placement in the HIV-positive
patients (E. F. Gherlone et al., 2015). Depending on definition of patient smoking status, the
included studies were classified into four categories according to the number of cigarettes smoked
per day; studies categorizing patients into three subgroups: non-smokers, <10 or >10 cigarettes per
day (Agliardi et al., 2010; Balderas Tamez et al., 2017; Bornstein et al., 2008; Brizuela et al.,
2014; Correia et al., 2017; E. F. Gherlone et al., 2015; Hinze et al., 2009; Peñarrocha et al., 2002;
Strietzel & Reichart, 2007; van Steenberghe et al., 2002), and none, <15 or >15 cigarettes per day
(Franceschetti et al., 2014; Guido Mangano & Ghertasi Oskouei, 2018; Habsha, 2000; Kan et al.,
1999; Testori et al., 2012), and none, <20 or >20 cigarettes per day (Agliardi et al., 2010; Arora et
al., 2017) and studies categorizing patients in four subgroups (none, 1-10, 10-20 or >20 cigarettes
per day) (Alsaadi et al., 2007, 2008; Cercadillo-Ibarguren et al., 2017; Nitzan et al., 2005;
Noguerol et al., 2006; Sanchez-Perez et al., 2007; Twito & Sade, 2014). The NOS score of the one

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 relevant article was less than six points (E. F. Gherlone et al., 2015). The results of the quality
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assessment of the studies are summarized in Table 3 (Table_3_SuppInfo.docx).
Meta-analysis Based on Implant-related Data

The results of the meta-analyses of implant failure/success were allocated into four subgroups
according to the definition of patient smoking status in studies:
(Ⅰ) (None, <10 or >10): fourteen papers were in this subgroup. A higher implant failure rate was
found in the patients who smoked <10 cigarettes/day (cigarettes per day) than in non-smokers; (P
= 0.046) (Table 4, Fig. 2). There was a statistically significantly increased risk of failure rates in
patients who smoked >10 cigarettes/day than in non-smokers (P < 0.001) (Table 4, Fig. 3).
Furthermore, patients who smoked >10 cigarettes/day showed higher implant failure rates than
those with a smoking rate less than 10 cigarettes/day (P < 0.001) (Table 4, Figure_4_SuppInfo.tif).
(Ⅱ) (None, <15 or >15): four papers were categorized in this subgroup. The pooled estimates of
studies demonstrated no statistically significant difference between the patients who smoked <15
cigarettes/day and non-smokers (P = 0.335) (Table 4, Figure_5_SuppInfo.tif). Patients who
smoked >15 cigarettes/day showed higher implant failure rates than non-smokers (P = 0.048)
(Table 4, Figure_6_SuppInfo.tif). There was no statistically significant difference between the
patients who smoked <15 cigarettes/day and those who smoked >15 cigarettes/day (P = 0.125)
(Table 4, Figure_7_SuppInfo.tif).
(Ⅲ) (None, <20 or >20): eight articles were included in this subgroup. A higher implant failure
rate was found in the patients who smoked <20 cigarettes/day than in non-smokers; (P < 0.001)
(Table 4, Fig. 8). Similarly, the patients who smoked >20 cigarettes/day had a higher rate of
implant failure than the non-smokers (P = 0.001) (Table 4, Fig. 9). There was no statistically
significant difference between the patients who smoked <20 cigarettes/day and those who smoked
>20 cigarettes/day (P = 0.118) (Table 4, Figure_10_SuppInfo.tif).
(Ⅳ) (None, 1-10, 10-20, or >20): seven studies were categorized in this subgroup. A higher
implant failure rate was found in the patients who smoked <10 cigarettes/day than the non-
smokers (P = 0.045) (Table 4, Figure_11_SuppInfo.tif). Patients who smoked 10-20 cigarettes/day
had a higher rate of implant failure than the non-smokers (P < 0.001) (Table 4,
Figure_12_SuppInfo.tif). There was also a statistically significantly increased risk of failure rate in
the patients who smoked >20 cigarettes/day than the non-smokers (P = 0.001) (Table 4,
Figure_13_SuppInfo.tif). There was no statistically significant difference between the patients

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 who smoked <10 cigarettes/day and those who smoked 10-20 cigarettes/day (P = 0.313) (Table 4,
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Figure_14_SuppInfo.tif). Finally, the patients who smoked >20 cigarettes/day had a higher rate of
implant failure than those who smoked 10-20 cigarettes/day (P < 0.001) (Table 4,
Figure_15_SuppInfo.tif).
Meta-analysis Based on Patient-related Data
The results of meta-analysis based on the patient-related data were allocated into three subgroups:
(Ⅰ) (None, <10 or >10): ten papers were in this subgroup. The pooled estimates of studies
demonstrated no statistically significant difference between the patients who smoked <10
cigarettes/day and the non-smokers (P = 0.956) (Table 5, Figure_16_SuppInfo.tif). There was a
statistically significantly increased risk of failure rate in the patients who smoked >10
cigarettes/day than the non-smokers (P = 0.002) (Table 5, Figure_17_SuppInfo.tif). Moreover,
there were not statistically significant differences in implant failure rates between the patients who
smoked <10 and those who smoked >10 cigarettes/day (P = 0.154) (Table 5,
Figure_18_SuppInfo.tif).
(Ⅱ) (None, <15 or >15): three papers were included in this subgroup. There was no statistically
significant difference between the patients who smoked <15 cigarettes/day and non-smokers; (P =
0.192) (Table 5, Figure_19_SuppInfo.tif). Patients who smoked >15 cigarettes/day showed higher
implant failure rates than non-smokers (P = 0.002) (Table 5, Figure_20_SuppInfo.tif). There was
no statistically significant difference between the patients who smoked <15 cigarettes/day and
those who smoked >15 cigarettes/day (P = 0.285) (Table 5, Figure_21_SuppInfo.tif).
(Ⅲ) (None, <20 or >20): There were four studies in this subgroup. A higher implant failure rate
was found in the patients who smoked <20 or >20 cigarettes/day than non-smokers (P<0.001)
(Table 5, Figure_22 and 23_SuppInfo.tif). There was no statistically significant difference
between the patients who smoked <20 cigarettes/day and those who smoked >20 cigarettes/day (P
= 0.172) (Table 5, Figure_24_SuppInfo.tif).
Subgroup Meta-analysis
Subgroups meta-analysis based on different implant surfaces was performed in each smoking
subgroup. In implant-related data, statistical significance implant failure RRs were observed for
implants with micro-rough surfaces in comparison with other implant surfaces in patients who
smoked <10, >10 and <20 cigarettes/day than non-smokers. In subgroup who smoked >10
cigarettes/day, significant differences in implant failure rates were also obtained in both turned and

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 rough surfaces than non-smokers. The RR for each subgroup examined is given in Table 6
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(Table_6_SuppInfo.docx).
Subgroups meta-analyses of studies with implants placed in the grafted sinuses were also
performed in groups who smoked <15 cigarettes/day and those who smoked >15 cigarettes/day.
There was an increase in the RR of implant failure in the implants placed in the grafted sinuses in
the patients who smoked >15 cigarettes/day (Table_7_SuppInfo.docx).
A meta-regression analysis considering the mean follow-up period as a covariate was performed
for each smoking subgroup. No significant relationship was found between the follow-up time and
implant failure rate in any of the smoking subgroups (Table_8_SuppInfo.docx).
Publication bias
In all meta-analyses, neither inspection of the funnel plot nor formal assessment using Egger’s test
showed any evidence of publication bias. The result of Egger’s test for each subgroup is given in
Table 9 (Table_9_SuppInfo.docx).
Discussion
The ability to predict the treatment outcomes is a substantial point in implant treatment settings.
Among the variety of conditions considered to affect the outcome of dental implants, increasing
attention has been concentrated on the patient-related risk factors (systemic and environmental
conditions, such as smoking) (Moy, Medina, Shetty, & Aghaloo, 2005). Recent meta-analyses
demonstrated a significant relationship between smoking and the risk of implant failure
(Chrcanovic et al., 2015; Moraschini, 2016). To the best of our knowledge, this is the first
systematic review and meta-analysis that evaluates the association between the heaviness of
smoking and implant failure. A new critical review has addressed this issue but has failed to
determine a cut-off point in terms of the quantity of daily cigarette consumption for dental implant
failure (Barzanji et al., 2018).
Meta-analyses based on implant-related data, as expected, demonstrated an increase in the RRs of
implant failure in all smoker subgroups than in non-smokers. Significantly enhanced failure risks
were obtained among all smoker subgroups compared with non-smokers except in the subgroups
who smoked <15 cigarettes/day. The findings showed the more cigarettes smoked daily, the more
probable was the dental implant failure.
Comparing the implant failure rate between the smoker subgroups considering different ranges of
cigarettes smoked per day, there was a statistically significant risk of implant failure between the
smokers who smoked <10 and those who smoked >10 cigarettes/day. There were no significant

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 differences between the other subgroups who smoked <15 vs. >15 and <20 vs. >20 cigarettes/day.
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Based on these findings, smoking less than 10 cigarettes/day can be recommended with caution as
a safe level for dental implant failure. The success rate of dental implants dropped considerably
when the patients smoked >10 cigarettes/day (Kullar & Miller, 2019). However, some authors
believe no level of cigarette consumption can be considered "safe" with respect to the risk of the
disease (Husten, 2009).
Detailed meta-analyses on the publications that categorized the patients into four subgroups
(None, 1-10, 10-20, or >20) revealed a significantly enhanced implant failure risk among the
patients who smoked 10-20 compared with the patients who smoked >20 cigarettes/day. No
statistically significant difference was found between the subgroups who smoked <10 and those
who smoked 10-20 cigarettes/day. These findings cautiously confirm that smoking more than one
pack/day can be considered a risk factor for implant failure. The domain of 10-20 cigarettes
smoked per day is an uncertain range for implant failure. It seems that implant failure operates
along a continuum with no apparent threshold of smoking level. It is recommended that cigarette
consumption data be analyzed as a continuous rather than as a categorical variable in the future
studies (Husten, 2009).
To eliminate the cumulative effects of the patient risk factors, the patient-related data were
analyzed separately. Similar to the meta-analyses based on the implant-related data, there was an
increase in the implant failure RRs in all smoker subgroups (except those who smoked <10
cigarettes/day) than in the non-smoker group. Significant differences were not found between the
patients who smoked <10 and <15 cigarettes/day and the non-smokers. A statistically significant
difference was obtained between the patients who smoked >10, >15, <20, and >20 cigarettes/day
and the non-smokers, which confirms the results of the implant-based meta-analyses. The results
highlight the risk of dental implant failure as a result of consuming more than one pack of
cigarettes a day. Comparing the implant failure between the smoker subgroups considering
different ranges of cigarettes smoked per day-despite the increase in the RRs of implant failure -
there were no significant differences between the subgroups who smoked <10 vs. >10 , <15 vs.
>15, and <20 vs. >20 cigarettes/day. This confirms that the probability of implant failure due to
smoking is continuously increased by increasing the smoking level.
It should be noted when implant failure is calculated with the patient as the statistical unit, the
statistical methodology can overestimate the outcome, resulting in a more negative outcome for
patients with multiple implants because when one implant is failed in a patient with multiple

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 implants, the patient's treatment outcome is considered a failure. In the patient-based meta-
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analyses on the patient subgroups smoking <20 or >20 cigarettes/day compared with non-smokers,
almost twice RRs of implant failure rate were obtained compared to the results of our implant-
based analyses, though surprisingly the RRs of the patient-based implant failure in the patient
subgroups smoking <10 or >10 cigarettes/day compared with non-smokers were nearly half of the
values of the implant-based analyses. In the patient subgroups smoking <15 or >15 cigarettes/day,
almost similar results were obtained in implant- and patient-based meta- analyses. However, it
should be noted that the number of studies included in the patient-based meta-analyses was less
than that of the studies included in the implant-based meta-analyses. Many studies only reported
the failure outcome based on the effects of smoking on the implant level, which may not have
taken into account the patients receiving multiple implants. It is recommended that dental implant
failure be reported on both implant- and patient-related basis in further studies.
In the selected articles, there was no uniform classification for the quantification of smoking
considering the number of cigarettes smoked per day. We found four different classifications
according to the patient’s cigarette consumption levels. There were some discrepancies in the
definition of heavy smokers in various studies. This heterogeneity made it difficult to compare the
data of the included studies. A patient self-reporting method was used to determine smoking status
in all studies. Using other accurate methods may be necessary to determine the actual patient
smoking status to investigate the true impact of smoking on implant failure.
Within our limitations, the results of this study should be interpreted with caution. In most selected
studies, smoking was rarely considered the main focus and was investigated as a complicating
factor involved in the implant success. Therefore, most of the studies included in the analysis were
of the cohort type, which could increase the probability of biases (J. Higgins & Green, 2008). The
present study might have been exposed to all of the inherent confounding factors in the included
articles and we might not have been able to control all of these restricting factors. The
methodological diversity in the selected papers could have affected the outcomes of the meta-
analysis. For example, sample size and follow-up periods of studies, presence of medical history,
site of implant placement, type of implants, presence of advanced surgeries like GBR, open sinus
lift, etc. might have impacted the results of analysis.
Half of the papers included in this meta-analysis had a short-term follow-up period, lower than 2
years. Most of them assessed the early implant failure, up to abutment connection. This may have
distorted the results of our study. However, no significant relationship was found between the

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 follow-up time and implant failure rate in any of the smoking subgroups in this study. Previous
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meta-analyses have reported that the implant failure rates do not increase linearly with an increase
in the follow-up time, indicating a higher risk of early vs. delayed implant failure due to smoking
(Moraschini, 2016; Strietzel et al., 2007).
Concerning the subgroup meta-analyses for the different implant surfaces, increased RRs of
implant failure were more highlighted in the micro-rough implants than in other implant surfaces.
In a recent meta-analysis, Chrcanovic et al. reported that implants with roughened surfaces had a
higher implant failure risk ratio in comparison with the turned implants in smokers (Chrcanovic et
al. 2015). This is in contrast with the studies reporting an association between smoking and
implant failure among the turned surfaces not the new implant surfaces (Balshe, Eckert, Koka,
Assad, & Weaver, 2008).
The subgroups meta-analysis also suggested an increase in the RR of implant failure for the
implants placed in the grafted sinuses in patients who smoked >15 cigarettes/day. The association
between smoking and implant failure in sites with grafted sinuses has been demonstrated in a
previous meta-analysis (Chambrone et al., 2014). Our results may suggest an increased risk of
implant failure in the grafted sinus sites in the heavy smokers.
In conclusion, within the limitation of this study, the results suggested that the risk of implant
failure was elevated with an increase in the number of cigarettes smoked per day. Smoking more
than one pack/day can be considered a risk factor for implant failure. Further studies are
suggested to investigate smoking as a continuous variable rather than a categorical one.
Acknowledgements

We would like to thank Dr. Aritza Brizuela, Dr. Paolo Cappa, Dr. Francisco Correia, Dr. Massimo
Del Fabbro, Dr. Devorah Schwartz-Arad, Dr. Frank Peter Strietzel, Dr. Leonardo Trombelli, and
Dr. Agurne Uribarri who provided us with some supplementary data about their studies, and Dr.
Marco Esposito, Dr. Sergio García-Bellosta, Dr. Effrat Habsha, Dr. Henri Tenenbaum, Dr Tobias
Thalmair, Dr. Maurizio S. Tonetti who kindly responded to our e-mail although it was not possible
for them to provide the requested data.

References

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 Agliardi, E., Clericò, M., Ciancio, P., & Massironi, D. (2010). Immediate loading of full-arch
Accepted Article fixed prostheses supported by axial and tilted implants for the treatment of edentulous
atrophic mandibles. Quintessence International, 41(4).
Albrektsson, T., Zarb, G., Worthington, P., & Eriksson, A. (1986). The long-term efficacy of
currently used dental implants: a review and proposed criteria of success. Int J Oral
Maxillofac Implants, 1(1), 11-25.
Alsaadi, G., Quirynen, M., Komarek, A., & van Steenberghe, D. (2007). Impact of local and
systemic factors on the incidence of oral implant failures, up to abutment connection. J
Clin Periodontol, 34(7), 610-617. doi:CPE1077 [pii]
10.1111/j.1600-051X.2007.01077.x [doi]
Alsaadi, G., Quirynen, M., Komarek, A., & van Steenberghe, D. (2008). Impact of local and
systemic factors on the incidence of late oral implant loss. Clin Oral Implants Res, 19(7),
670-676. doi:CLR1534 [pii]
10.1111/j.1600-0501.2008.01534.x [doi]
Arora, A., Reddy, M. M., Mhatre, S., Bajaj, A., Gopinath, P. V., & Arvind, P. (2017).
Comparative evaluation of effect of smoking on survival of dental implant. Journal of
International Oral Health, 9(1), 24-27. doi:10.4103/0976-7428.201094
Balderas Tamez, J. E., Neri Zilli, F., Fandiño, L. A., & Guizar, J. M. (2017). Factors related to the
success or failure of dental implants placed in the specialty prosthodontics and
implantology at Universidad of La Salle Bajio. Revista Espanola de Cirugia Oral y
Maxilofacial, 39(2), 63-71. doi:10.1016/j.maxilo.2016.02.001
Balshe, A. A., Eckert, S. E., Koka, S., Assad, D. A., & Weaver, A. L. (2008). The effects of
smoking on the survival of smooth-and rough-surface dental implants. International
Journal of Oral & Maxillofacial Implants, 23(6).
Barzanji, A., Chatzopoulou, D., & Gillam, D. (2018). Impact of Smoking as a Risk Factor for
Dental Implant Failure: A Critical Review. BAOJ Dentistry.
Bornstein, M. M., Cionca, N., & Mombelli, A. (2009). Systemic conditions and treatments as risks
for implant therapy. Int J Oral Maxillofac Implants, 24(Suppl), 12-27.
Bornstein, M. M., Halbritter, S., Harnisch, H., Weber, H.-P., & Buser, D. (2008). A retrospective
analysis of patients referred for implant placement to a specialty clinic: indications,
surgical procedures, and early failures. The International journal of oral & maxillofacial
implants, 23(6), 1109.

This article is protected by copyright. All rights reserved

 Brizuela, A., Martín, N., Fernández, F. J., Larrazábal, C., & Anta, A. (2014). Osteotome sinus
Accepted Article floor elevation without grafting material: Results of a 2-year prospective study. Journal of
Clinical and Experimental Dentistry, 6(5), e479-e484. doi:10.4317/jced.51576
Buser, D., Mericske‐stern, R., Pierre Bernard, J. P., Behneke, A., Behneke, N., Hirt, H. P., . . .
Lang, N. P. (1997). Long‐term evaluation of non‐submerged ITI implants. Part 1: 8‐year
life table analysis of a prospective multi‐center study with 2359 implants. Clinical Oral
Implants Research, 8(3), 161-172.
Calsina, G., Ramón, J. M., & Echeverría, J. J. (2002). Effects of smoking on periodontal tissues.
Journal of Clinical Periodontology, 29(8), 771-776.
Cercadillo-Ibarguren, I., Sánchez-Torres, A., Figueiredo, R., & Valmaseda-Castellón, E. (2017).
Bimaxillary simultaneous immediate loading of full-arch restorations: A case series.
Journal of Clinical and Experimental Dentistry, 9(9), e1147-e1152.
doi:10.4317/jced.54172
Chambrone, L., Preshaw, P. M., Ferreira, J. D., Rodrigues, J. A., Cassoni, A., & Shibli, J. A.
(2014). Effects of tobacco smoking on the survival rate of dental implants placed in areas
of maxillary sinus floor augmentation: a systematic review. Clin Oral Implants Res, 25(4),
408-416. doi:10.1111/clr.12186 [doi]
Chen, H., Liu, N., Xu, X., Qu, X., & Lu, E. (2013). Smoking, radiotherapy, diabetes and
osteoporosis as risk factors for dental implant failure: a meta-analysis. PLoS One, 8(8),
e71955. doi:10.1371/journal.pone.0071955 [doi]
PONE-D-13-12119 [pii]
Chrcanovic, B. R., Albrektsson, T., & Wennerberg, A. (2015). Smoking and dental implants: A
systematic review and meta-analysis. J Dent. doi:S0300-5712(15)00060-3 [pii]
10.1016/j.jdent.2015.03.003 [doi]
Cochran, D. L., Buser, D., Ten Bruggenkate, C. M., Weingart, D., Taylor, T. M., Bernard, J. P., . .
. Simpson, J. P. (2002). The use of reduced healing times on ITI® implants with a
sandblasted and acid‐etched (SLA) surface: early results from clinical trials on ITI® SLA
implants. Clinical Oral Implants Research, 13(2), 144-153.
Correia, F., Gouveia, S., Felino, A. C., Costa, A. L., & Almeida, R. F. (2017). Survival rate of
dental implants in patients with history of periodontal disease: A retrospective cohort
study. International Journal of Oral and Maxillofacial Implants, 32(4), 927-934.
doi:10.11607/jomi.3732

This article is protected by copyright. All rights reserved

 Fleiss, J., Levin, B., & Paik, M. (1981). Statistical Methods for Rates and Proportions (2nd
Accepted Article edition ed.). New York: John Wiley & Sons.
Franceschetti, G., Farina, R., Stacchi, C., Di Lenarda, R., Di Raimondo, R., & Trombelli, L.
(2014). Radiographic outcomes of transcrestal sinus floor elevation performed with a
minimally invasive technique in smoker and non-smoker patients. Clin Oral Implants Res,
25(4), 493-499. doi:10.1111/clr.12188 [doi]
Gherlone, E. F., Cappare, P., Tecco, S., Polizzi, E., Pantaleo, G., Gastaldi, G., & Grusovin, M. G.
(2015). A Prospective Longitudinal Study on Implant Prosthetic Rehabilitation in
Controlled HIV-Positive Patients with 1-Year Follow-Up: The Role of CD4+ Level,
Smoking Habits, and Oral Hygiene. Clin Implant Dent Relat Res, 4(10), 12370.
Gherlone, E. F., Capparé, P., Tecco, S., Polizzi, E., Pantaleo, G., Gastaldi, G., & Grusovin, M. G.
(2016). Implant prosthetic rehabilitation in controlled HIV‐positive patients: a prospective
longitudinal study with 1‐year follow‐up. Clinical implant dentistry and related research,
18(4), 725-734.
Guido Mangano, F., & Ghertasi Oskouei, S. (2018). Low serum vitamin D and early dental
implant failure: Is there a connection? A retrospective clinical study on 1740 implants
placed in 885 patients. 12(3), 174-182. doi:10.15171/joddd.2018.027
Habsha, E. (2000). Survival of osseointegrated dental implants in smokers and non-smokers.
University of Toronto.
Heitz‐Mayfield, L. J. (2008). Peri‐implant diseases: diagnosis and risk indicators. Journal of
Clinical Periodontology, 35, 292-304.
Herrmann, I., Lekholm, U., & Holm, S. (2003). Statistical outcome of random versus selected
withdrawal of dental implants. International Journal of Prosthodontics, 16(1).
Herrmann, I., Lekholm, U., Holm, S., & Karlsson, S. (1999). Impact of implant interdependency
when evaluating success rates: a statistical analysis of multicenter results. International
Journal of Prosthodontics, 12(2).
Higgins, J., & Green, S. (2008). Cochrane Collaboration Cochrane handbook for systematic
reviews of interventions. Chichester, England: Wiley-Blackwell.
Higgins, J. P., & Thompson, S. G. (2002). Quantifying heterogeneity in a meta‐analysis. Statistics
in medicine, 21(11), 1539-1558.
Hinze, M., Thalmair, T., Bolz, W., & Wachtel, H. (2009). Immediate loading of fixed provisional
prostheses using four implants for the rehabilitation of the edentulous arch: a prospective

This article is protected by copyright. All rights reserved

Accepted Article clinical study. The International journal of oral & maxillofacial implants, 25(5), 1011-
1018.
Husten, C. G. (2009). How should we define light or intermittent smoking? Does it matter?
Nicotine & Tobacco Research, 11(2), 111.
Jansson, L., & Lavstedt, S. (2002). Influence of smoking on marginal bone loss and tooth loss–a
prospective study over 20 years. Journal of Clinical Periodontology, 29(8), 750-756.
Johnson, N., & Bain, C. (2000). Tobacco and oral disease. British Dental Journal, 189(4).
Kan, J. Y. K., Rungcharassaeng, K., Lozada, J. L., & Goodacre, C. J. (1999). Effects of smoking
on implant success in grafted maxillary sinuses. Journal of Prosthetic Dentistry, 82(3),
307-311. doi:10.1016/s0022-3913(99)70085-5
Kullar, A. S., & Miller, C. S. (2019). Are There Contraindications for Placing Dental Implants?
Dental Clinics, 63(3), 345-362.
Levin, L., Laviv, A., & Schwartz‐Arad, D. (2006). Long‐term success of implants replacing a
single molar. Journal of Periodontology, 77(9), 1528-1532.
Lipsey, M. W., & Wilson, D. B. (2001). Practical meta-analysis: SAGE publications, Inc.
Mir-Mari, J., Mir-Orfila, P., Valmaseda-Castellon, E., & Gay-Escoda, C. (2012). Long-term
marginal bone loss in 217 machined-surface implants placed in 68 patients with 5 to 9
years of follow-up: a retrospective study. Int J Oral Maxillofac Implants, 27(5), 1163-
1169.
Moher, D., Liberati, A., Tetzlaff, J., & Altman, D. G. (2009). Preferred reporting items for
systematic reviews and meta-analyses: the PRISMA statement. Annals of internal
medicine, 151(4), 264-269.
Moraschini, V. (2016). Success of dental implants in smokers and non-smokers: a systematic
review and meta-analysis. International journal of oral and maxillofacial surgery, 45(2),
205-215.
Moy, P. K., Medina, D., Shetty, V., & Aghaloo, T. L. (2005). Dental implant failure rates and
associated risk factors. International Journal of Oral & Maxillofacial Implants, 20(4).
Nitzan, D., Mamlider, A., Levin, L., & Schwartz-Arad, D. (2005). Impact of smoking on marginal
bone loss. Int J Oral Maxillofac Implants, 20(4), 605-609.
Noguerol, B., Munoz, R., Mesa, F., de Dios Luna, J., & O'Valle, F. (2006). Early implant failure.
Prognostic capacity of Periotest((R)): retrospective study of a large sample. Clinical Oral
Implants Research, 17(4), 459-464. doi:10.1111/j.1600-0501.2006.01250.x

This article is protected by copyright. All rights reserved

 Palma-Carrió, C., Maestre-Ferrín, L., Peñarrocha-Oltra, D., Peñarrocha-Diago, M. A., &
Accepted Article Peñarrocha-Diago, M. (2011). Risk factors associated with early failure of dental implants.
A literature review. Med Oral Patol Oral Cir Bucal, 16(4), e514-517.
Peñarrocha, M., Guarinos, J., Sanchis, J. M., & Balaguer, J. (2002). A retrospective study (1994-
1999) of 441 ITI® implants in 114 patients followed-up during an average of 2.3 years.
Medicina Oral, 7(2), 144-155.
Peterson, J., Welch, V., Losos, M., & Tugwell, P. (2011). The Newcastle-Ottawa scale (NOS) for
assessing the quality of nonrandomised studies in meta-analyses. Ottawa: Ottawa Hospital
Research Institute.
Qian, J., Wennerberg, A., & Albrektsson, T. (2012). Reasons for marginal bone loss around oral
implants. Clinical implant dentistry and related research, 14(6), 792-807.
Renvert, S., & Quirynen, M. (2015). Risk indicators for peri‐implantitis. A narrative review.
Clinical Oral Implants Research, 26, 15-44.
Sanchez-Perez, A., Moya-Villaescusa, M. J., & Caffesse, R. G. (2007). Tobacco as a risk factor
for survival of dental implants. J Periodontol, 78(2), 351-359.
doi:10.1902/jop.2007.060299 [doi]
Schwartz‐Arad, D., Herzberg, R., & Levin, L. (2005). Evaluation of long‐term implant success.
Journal of Periodontology, 76(10), 1623-1628.
Smith, D. E., & Zarb, G. A. (1989). Criteria for success of osseointegrated endosseous implants.
The Journal of prosthetic dentistry, 62(5), 567-572.
Strietzel, F. P., & Reichart, P. A. (2007). Oral rehabilitation using Camlog screw-cylinder
implants with a particle-blasted and acid-etched microstructured surface. Results from a
prospective study with special consideration of short implants. Clin Oral Implants Res,
18(5), 591-600. doi:CLR1375 [pii]
10.1111/j.1600-0501.2007.01375.x [doi]
Strietzel, F. P., Reichart, P. A., Kale, A., Kulkarni, M., Wegner, B., & Kuchler, I. (2007). Smoking
interferes with the prognosis of dental implant treatment: a systematic review and meta-
analysis. J Clin Periodontol, 34(6), 523-544. doi:CPE1083 [pii]
10.1111/j.1600-051X.2007.01083.x [doi]
Testori, T., Weinstein, R. L., Taschieri, S., & Del Fabbro, M. (2012). Risk factor analysis
following maxillary sinus augmentation: a retrospective multicenter study. Int J Oral
Maxillofac Implants, 27(5), 1170-1176.

This article is protected by copyright. All rights reserved

 Twito, D., & Sade, P. (2014). The effect of cigarette smoking habits on the outcome of dental
Accepted Article implant treatment. PeerJ, 2, e546. doi:10.7717/peerj.546 [doi]
546 [pii]
van Steenberghe, D., Facobs, R., Desnyder, M., Maffei, G., & Quirynen, M. (2002). The relative
impact of local and endogenous patient-related factors on implant failure up to the
abutment stage. Clinical Oral Implants Research, 13(6), 617-622. doi:10.1034/j.1600-
0501.2002.130607.x

Tables
Table 4. Meta-analysis of the smoking subgroups based on the implant-related data.

Subgroups Heterogeneity Fixed- or Relative 95% P value for

Random- risks Confidence overall
I2 % P value effects model Interval effect

Ⅰ None vs. <10 12.4% P = 0.317 Fixed 1.28 (1-1.64) P = 0.046

None vs. >10 53.8% p = 0.009 Random 2.4 (1.71-3.36) P < 0.001
<10 vs. >10 35.4% p = 0.092 Fixed 1.69 (1.31-2.17) P < 0.001
Ⅱ None vs. <15 37.9% P = 0.185 Fixed 1.29 (0.77-2.17) P = 0.335
None vs. >15 82.1% P = 0.001 Random 2.82 (1.01-7.9) P = 0.048
<15 vs. >15 23% P = 0.273 Fixed 1.54 (0.89-2.69) P = 0.125
Ⅲ None vs. <20 5.7% P = 0. 386 Fixed 1.46 (1.22-1.76) P < 0.001
None vs. >20 71% P = 0.001 Random 2.51 (1.47-4.28) P = 0.001
<20 vs. >20 70.9% P = 0.001 Random 1.6 (0.89-2.86) P = 0.118
Ⅳ None vs. 1-10 0% P = 0.524 Fixed 1.31 (1.01-1.7) P = 0.045
None vs. 10-20 34.4% P = 0.166 Fixed 1.53 (1.22-1.93) P < 0.001
None vs. >20 74.3% P = 0.001 Random 2.48 (1.46-4.22) P = 0.001
1-10 vs. 10-20 0% P = 0.644 Fixed 1.18 (0.86-1.62) P = 0.313
10-20 vs. >20 76.2% P < 0.001 Random 1.74 (1.33-2.26) P < 0.001
Accepted Article
Table 5. Meta-analysis of the smoking subgroups based on the patient-related data.

Heterogeneity Fixed- or Relative 95% P value for

Subgroups Random- risks Confidence overall effect
I2 % P value effects Interval
model
Ⅰ None vs. <10 0.0% P = 0.512 Fixed 0.99 (0.63-1.56) P = 0.956
None vs. >10 7.4% P = 0.373 Fixed 1.56 (1.18-2.06) P = 0.002
<10 vs. >10 0.0% P = 0.489 Fixed 1.44 (0.87-2.36) P = 0.154
Ⅱ None vs. <15 0.0% P = 0.702 Fixed 1.64 (0.78-3.46) P = 0.192
None vs. >15 0.0% P = 0.941 Fixed 2.73 (1.42-5.24) P = 0.002
<15 vs. >15 0.0% P = 0.660 Fixed 1.65 (0.66-4.12) P = 0.285
Ⅲ None vs. <20 0.0% P = 0.427 Fixed 2.82 (1.87-4.25) P < 0.001
None vs. >20 7.9% P = 0.354 Fixed 4 (2.72-5.89) P < 0.001
<20 vs. >20 0.0% P = 0.845 Fixed 1.35 (0.88-2.09) P = 0.172

Figure Legends
Fig. 1. Flow diagram of the selection process

Fig. 2. Forest plot for the event “implant failure between the patient who smoked <10
cigarettes/day and non-smokers” based on the implant-related data

Fig. 3. Forest plot for the event “implant failure between the patient who smoked >10
cigarettes/day and non-smokers” based on the implant-related data

Fig. 8. Forest plot for the event “implant failure between the patient who smoked <20
cigarettes/day and non-smokers” based on the implant-related data

Fig. 9. Forest plot for the event “implant failure between the patient who smoked >20
cigarettes/day and non-smokers” based on the implant-related data

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