
==== Front
Nicotine Tob Res
Nicotine Tob Res
nictob
Nicotine & Tobacco Research
1462-2203
1469-994X
Oxford University Press US

38618685
10.1093/ntr/ntae085
ntae085
Review
AcademicSubjects/MED00010
AcademicSubjects/SOC02541
Editor's Choice
The Effect of Nicotine-Containing Products on Peri-Implant Tissues: A Systematic Review and Network Meta-Analysis
Vámos Orsolya DMD Department of Prosthodontics, Semmelweis University, Budapest, Hungary
Centre for Translational Medicine, Semmelweis University, Budapest, Hungary

Komora Péter DMD Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
Department of Restorative Dentistry and Endodontics, Semmelweis University, Budapest, Hungary

Gede Noémi PhD Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary

Hegyi Péter PhD Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary
Institute of Pancreatic Diseases, Semmelweis University, Budapest, Hungary

Kelemen Kata DMD Department of Prosthodontics, Semmelweis University, Budapest, Hungary
Centre for Translational Medicine, Semmelweis University, Budapest, Hungary

Varga Gábor PhD Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
Department of Oral Biology, Semmelweis University, Budapest, Hungary

Mikulás Krisztina PhD Department of Prosthodontics, Semmelweis University, Budapest, Hungary
Centre for Translational Medicine, Semmelweis University, Budapest, Hungary

Kerémi Beáta PhD Centre for Translational Medicine, Semmelweis University, Budapest, Hungary
Department of Restorative Dentistry and Endodontics, Semmelweis University, Budapest, Hungary

https://orcid.org/0000-0002-0530-0905
Kispélyi Barbara PhD Department of Prosthodontics, Semmelweis University, Budapest, Hungary
Centre for Translational Medicine, Semmelweis University, Budapest, Hungary

Corresponding Author: Barbara Kispélyi, PhD, Department of Prosthodontics, Semmelweis University, Szentkirályi utca 47, 1088 Budapest, Hungary. Telephone: 36208250338; Fax: 3613175270; E-mail: kispelyi.barbara@semmelweis.hu
10 2024
15 4 2024
15 4 2024
26 10 12761285
19 10 2023
08 4 2024
10 4 2024
20 6 2024
© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.

Abstract

Introduction

Smokers have a higher chance of developing peri-implant diseases and are therefore considered an at-risk population. Our aim was to compare peri-implant characteristics in users of electronic cigarettes (EC), waterpipes (WP), cigarettes (CS), smokeless tobacco (ST), and nonsmokers (nonusers of any nicotine and tobacco product; NS).

Aims and Methods

A systematic search of four electronic databases (PubMed, EMBASE, Web of Science, and CENTRAL) was performed until April 2023, restricted to English language. Thirty-nine observational studies were included in the qualitative synthesis, of which 32 studies were included in a Bayesian network meta-analysis. Using a predesigned form, two researchers independently collected data about marginal bone loss (MBL), probing pocket depth (PPD), plaque index, bleeding on probing, modified plaque index, probing pocket depth > 4 mm (PPD > 4), gingival index, peri-implant sulcular fluid volume, and TNF-α and IL-1β levels. QUIPS and CINeMA were used to evaluate the risk of bias and certainty of evidence.

Results

Nonsmokers had the smallest MBL. Most nicotine-containing product users had significantly higher MBL (CS, mean difference [MD]: 1.34 credible interval [CrI]: 0.85, 1.79; WP, MD: 1.58 CrI: 0.84, 2.35; ST, MD: 2.53, CrI: 1.20, 3.87) than NS. Electronic cigarettes did not show significant difference compared to NS (MD: 0.52 CrI: −0.33, 1.36). In secondary outcomes, NS were ranked in first place. Subset analysis based on smoking habit, implant duration, and maintenance control revealed no differences in ranking probability.

Conclusions

Most nicotine-containing product users presented worse peri-implant parameters compared to NS, while EC users did not show significant differences to NS in many outcomes.

Implications

Alternative nicotine-containing products are gaining popularity and are often considered less harmful by the general public compared to traditional cigarettes. This is the first network meta-analysis comparing users of four nicotine-containing products and NS. This study shows that CS, WP, and ST have a detrimental effect on the overall health of peri-implant tissues. EC users also presented inferior parameters compared to NS; however, the difference was not significant in many outcomes. It is essential to educate patients who are using nicotine-containing products, and to provide proper maintenance and appropriate cessation support. Well-designed multiarmed studies are needed for direct comparison of different products, including heated tobacco products. Greater transparency of confounding factors is needed regarding smoking habit and oral hygiene.

Centre for Translational Medicine, Semmelweis University
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pmcIntroduction

Dental implants are presently a safe option for tooth replacement, regardless of the cause of tooth loss.1 The cumulative survival rate for implants in healthy patients is 96.1% over 10 years and 83.8% over 25 years.2,3 However, complications like peri-implant mucositis or peri-implantitis are frequently identified and diagnosed and if not treated, patients can lose implants.4

Smoking is known to be a contributing factor that increases the chance of implant failure rates and postoperative infections.5 Several studies have demonstrated that tobacco use compromises the clinico-radiographic, microbiological, and immunoinflammatory status of dental implants over time.6,7

While global smoking rates are decreasing,8 alternative nicotine-containing products (eg, electronic cigarettes, heated tobacco products, smokeless tobacco, waterpipes) have gained popularity in recent years, especially among the younger population.9 Alternative nicotine-containing products are often perceived as a relatively safer alternative than traditional cigarettes.10 Nicotine e-cigarettes have been demonstrated to be more effective in smoking cessation than traditional nicotine-replacement therapy,11 although recently there has been growing concern over their safety to cardiopulmonary health.12

Recent meta-analyses investigated the effect of waterpipes13 and electronic cigarettes on periodontal14 and peri-implant parameters.15 However, there is a lack of comprehensive analysis comparing the effects of traditional cigarettes, electronic cigarettes, waterpipes, and smokeless tobacco on peri-implant health. Therefore, the aim of this network meta-analysis (NMA) and systematic review was to investigate the clinical, radiographic, and immunological peri-implant parameters in users of different types of nicotine-containing products and nonsmokers (NS). We hypothesized that users of all nicotine-containing products would have worse clinico-radiographic and immunological peri-implant parameters compared to nonsmokers.

Methods

Protocol and Registration

Our systematic review and meta-analysis are reported in accordance with the recommendations of the PRISMA 2020 guideline,16 while the Cochrane Handbook17 has been followed. The protocol of the study was registered on PROSPERO International Prospective Register of Systematic Reviews (registration number CRD42022375399).

Eligibility Criteria

Studies assessing the peri-implant health of various nicotine-containing product users and nonsmokers were considered eligible for our systematic review and meta-analysis. We defined a question and created a PECO (patient/population-exposure-control-outcome) framework:

Population (P): patients with dental implants

Exposure (E): different types of nicotine-containing products:traditional cigarette (E1), electronic cigarette (E2), waterpipe (E3), and smokeless tobacco (E4)

Control (C): nonsmokers (nonusers of any nicotine and tobacco product)

Outcome (O): primary outcome: peri-implant crestal bone loss measured in millimeters; secondary outcome: clinical and immunological peri-implant parameters examined in the study: probing pocket depth (PPD), bleeding on probing (BOP), plaque index (PI), gingival index (GI), peri-implant sulcular fluid (PISF) volume, and levels of proinflammatory cytokines (TNF-α and IL-1β)

We excluded case reports, case series, animal studies, in vitro research, review articles, abstracts, posters, letters, and editorials. Articles written in English language were screened. Studies of patients with diagnosed systemic conditions or peri-implant diseases were excluded. We excluded patients who had received implants less than 1 year prior.

Information Sources and Search Strategy

A systematic search of four electronic databases (PubMed [MEDLINE], EMBASE, Web of Science, and Cochrane Library [Cochrane Central Register of Controlled Trials—CENTRAL]) was in April 2023. Our search strategy corresponded to the PECO framework. We searched for all published English articles. Also, the reference lists of eligible publications and review articles were evaluated.

For each database, the following search query was employed: (Electronic cigarette OR e-cigarette OR vaping OR nicotine OR cigarette OR smoking OR smoker OR tobacco OR waterpipe OR water pipe OR smokeless OR betel) AND (implant OR peri-implant OR peri-implant).

On PubMed, Web of Science, and Cochrane Library no filters were applied, while a title and abstract filter were applied on EMBASE.

Selection Process

After conducting a systematic search, the references were imported into a citation management program (Rayyan)18 and screened for duplicates, which were deleted both automatically and manually. After removing duplicates, two review authors (VO and KP) independently examined titles, abstracts, and full texts against specified eligibility criteria. Throughout the selection procedure, Cohen’s kappa coefficient19 was determined to evaluate interrater reliability. A third reviewer (KK) resolved the disagreements.

Data Collection Process and Data Items

Using a standardized data collection form, two separate reviewers (VO and KP) extracted data, and a third independent reviewer (KK) settled any discrepancies. The following data were extracted from each eligible article: first author, year of publication, country, digital object identifier, study design, study period, patient demographics, type of nicotine-containing product used, number and position of implants, duration and frequency of smoking, family history of smoking, oral hygiene habits, mean and standard deviation of the outcomes.

Study Risk of Bias Assessment

Risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool.20 The QUIPS tool uses six important domains that should be critically appraised: study participation, study attrition, prognostic factor measurement, outcome measurement, study confounding, statistical analysis, and reporting. Each domain comprises numerous items that are evaluated individually. Based on the ratings of the included items, a conclusive judgment of the risk of bias in each domain is made and expressed on a three-grade scale (high, moderate, or low).20 Two independent review authors (VO and KP) evaluated the included records separately, and any disagreements between them were discussed until a consensus was reached. A third review author (KK) was consulted to resolve conflicts.

Certainty of Evidence

The certainty of evidence was determined using the Confidence in Network Meta-Analysis (CINeMA)21 web application. Within-study bias, reporting bias, indirectness, imprecision, heterogeneity, and incoherence were evaluated.

Synthesis Methods and Effect Measures

The minimum number of treatments/interventions was three in the main part(s) of the network—where the comparator treatments/interventions must be the same in the studies—for performing a Bayesian Network Meta-Analysis. As we assumed considerable between-study heterogeneity in all cases, a random-effects model was used to pool effect sizes. We optimized the model and generated posterior samples using the Monte Carlo methods.

For continuous outcomes, the mean difference (MD) with a 95% credible interval (CrI) was used as the effect size measure. To calculate the pooled difference, the sample size, mean, and standard deviation (SD) from each study were extracted. If the standard deviation (SD) was not provided, but the standard error (SE) or confidence interval was, we calculated the SD based on the SE or confidence interval (eg, by multiplying the SE by the square root of the sample size or by using the t-distribution value for the confidence interval based on the confidence level provided).

The treatments/interventions were visualized on a network plot, with the nodes representing the different treatments/interventions and the edges representing direct comparisons. A summary of the network characteristics was performed for each network. It includes the number of interventions, studies, patients in the network, total number of feasible pairwise comparisons, total number of pairwise comparisons with direct data, number of two-arm studies, and number of multiarm studies. A league table was created to display the network estimates (pooled estimates of direct and indirect data) for each treatment/intervention. By determining the surface under the cumulative ranking (SUCRA) curve values, the interventions were ordered by their posterior probability. The SUCRA scale ranges from 0 to 100%. The higher the SUCRA value and the closer it is to 100%, the more likely a therapy is in the top rank or one of the top rankings; the lower the SUCRA value and the closer it is to 0 the more likely a therapy is in the bottom rank or one of the bottom ranks. The consistency is examined with a plot, which can help identify loops where the inconsistency is present. The statistical analysis of the data was conducted using the R software (R Core Team, 2019, Vienna, Austria) using the BUGSnet (Audrey Beliveau, 2021. Bayesian network meta-analyses in compliance with best practice and reporting guidelines. https://github.com/audrey-b/BUGSnet/) packages for calculations.22

Results

Search and Selection

The search query yielded a total of 10 282 records. After duplicate removal, a total of 6362 studies underwent title and abstract selection with a Cohen’s Kappa agreement score of 0.88. Subsequently, 92 articles underwent full-text screening with a Cohen’s Kappa agreement score of 0.91. After the selection process (Figure 1), a total of 39 studies7,23–60 were included in the qualitative synthesis, of which 327,23–26,28–31,33–36,39–46,48,50,51,53–60 were suitable for inclusion in the quantitative synthesis. The reference lists of the included articles were analyzed using a citation chaser program. Following a comprehensive process of backward and forward chasing, one additional eligible article was included in our analysis.

Figure 1. Study selection process, PRISMA flowchart containing results of systematic search and article selection. *Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). **If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools.16

Basic Characteristics of the Included Studies

All included studies were published in English between 1996 and 2022. Case-control, cross-sectional, and cohort observational studies were included in our analysis (Supplementary Table 1).

Risk of Bias

Out of the 39 included studies, nine were judged to have an overall low risk of bias, 10 of them were judged to have a moderate risk of bias, and 20 of them were judged to have an overall high risk of bias (Supplementary Document 1, Supplementary Figure 1.1). Specific limitations included the lack of information on the population included, bias because of prognostic factor measurement, and bias because of adjustment for confounders.

Synthesis of the Results

Thirty-two studies7,23–26,28–31,33–36,39–46,48,50,51,53–60 were included in the NMA. Network characteristic tables, including the most important data for each group, were used to describe the results of each analysis (Supplementary Document 2).

Primary Outcome—Marginal Bone Loss

The network (Figure 2A) includes 25 studies.7,23–26,28–31,33,34,36,39,41,42,45,46,48,51,54,56–60 The total number of examined implants in the network is 4049. SUCRA values (Figure 2B) indicate that NS are likely to have the smallest marginal bone loss (SUCRA: 97.17%) followed by electronic cigarette users (SUCRA: 75.95%). Cigarettes (CS), waterpipes (WP), and smokeless tobacco (ST) were ranked, respectively (SUCRA: 43.12%, 29.54%, 4.2%). Heat plot for marginal bone loss (Figure 2C) represents the pairwise comparisons of different nicotine-containing product users and nonsmokers. CS (MD: 1.34 CrI: 0.85, 1.79) and WP (MD: 1.58 CrI: 0.84, 2.35) had significantly higher marginal bone loss than NS, while ST had significantly higher marginal bone loss compared to NS (MD: 2.53, CrI: 1.20, 3.87) and electronic cigarettes (EC) (MD: 2.01 CrI:0.40, 3.6). When examining the consistency-inconsistency plot, points that are further to the 45° line indicate the existence of bias or noticeable heterogeneity. Examining the MBL, we observe that none of the data points are beyond the consistency-inconsistency line (Figure 2D), indicating that we did not find any significant heterogeneity.

Figure 2. (A) Network geometry of the eligible comparisons of marginal bone loss in different nicotine-containing product user groups and nonsmokers; (B) the league-heat diagram shows the mean difference and 95% credible interval for all possible treatment pairs, with CS, WP, and ST showing statistically higher marginal bone loss (MBL) than NS; ST has statistically higher MBL than EC; (C) surface under the cumulative ranking curves (SUCRA%) values of marginal bone loss, NS has the greatest likelihood of ranking first. Second, EC has the highest probability of reaching one of the top rankings; and (D) the consistency-inconsistency plot reveals no significant heterogeneity. CS = cigarette smokers; EC = electronic cigarette; NS = nonsmokers; ST = smokeless tobacco; WP = waterpipe.

Secondary Outcomes

Probing Pocket Depth

The network (Figure 3A) includes 18 studies.23–25,31,33–36,39,41,43,44,48,52,53,59,60 The total number of examined implants in the network is 3296. SUCRA values (Figure 3C) indicate that NS are likely to have the smallest PPD (SUCRA: 95.46%) followed by EC (SUCRA: 67.22%). CS, WP, ST were ranked, respectively (SUCRA: 58.34%, 20.95%, 8.04%). Heat plot for PPD (Figure 3B) represents the pairwise comparisons of different nicotine-containing product users and nonsmokers. CS (MD: 0.90 CrI: 0.29, 1.54), WP (MD: 2.16 CrI: 0.29, 3.39), and ST (MD: 3.11 CrI: 0.84, 5.42) users had significantly higher PPD than NS, while no statistically significant differences were detected between the different nicotine-containing products. The consistency-inconsistency plot (Figure 3D) shows no remarkable heterogeneity.

Figure 3. (A) Network geometry of the eligible comparisons of probing pocket depth in different nicotine-containing product user groups and nonsmokers; (B) the league-heat diagram shows the mean difference and 95% credible interval for all possible treatment pairs, with CS, WP, and ST showing statistically higher probing pocket depth (PPD) than NS; (C) surface under the cumulative ranking curves (SUCRA%) values of PPD, NS has the greatest likelihood of ranking first. Secondly, EC, then thirdly, CS has the highest probability of reaching one of the top rankings; and (D) the consistency-inconsistency plot reveals no significant heterogeneity. CS = cigarette smokers; EC = electronic cigarette; NS = nonsmokers; ST = smokeless tobacco; WP = waterpipe.

Plaque Index

The network (Figure 4A) includes 17 studies.7,23–26,29–31,35,36,40–42,46,53,57,58 The total number of examined implants in the network is 2049. SUCRA values (Figure 4C) indicate that NS are likely to have the smallest PI (SUCRA: 99.38%) followed by EC (SUCRA: 72.84%). CS, WP, ST were ranked respectively (SUCRA: 33.18%, 27.19%, 17.43%). Heat plot for plaque index (Figure 4B) represents the pairwise comparisons of different nicotine-containing product users and nonsmokers. EC (MD: 8.25 CrI: 0.44, 16.7), CS (MD: 17.45, CrI: 12.25, 22.55), WP (MD: 18.29 CrI: 11.65, 24.81), and ST (MD: 22.01 CrI: 5.30, 39.21) had significantly higher plaque index than NS. CS (MD: 9.20 CrI: 0.69, 17.51) and WP (MD: 10.04 CrI: 0.52, 19.09) had statistically significantly higher plaque index compared to EC. The consistency-inconsistency plot (Figure 4D) shows no remarkable heterogeneity.

Figure 4. (A) Network geometry of the eligible comparisons of plaque index in different nicotine-containing product user groups and nonsmokers; (B) the league-heat diagram contains the mean difference and 95% credible interval for all possible treatment pairs, all nicotine-containing product users have statistically higher plaque index (PI) than NS; CS and WP have statistically higher PI than EC; (C) surface under the cumulative ranking curves (SUCRA%) values of PI, NS has the greatest likelihood of ranking first. Secondly, EC has the highest probability of reaching one of the top rankings; and (D) the consistency-inconsistency plot reveals no significant heterogeneity. CS = cigarette smokers; EC = electronic cigarette; NS = nonsmokers; ST = smokeless tobacco; WP = waterpipe.

Bleeding on Probing

The network (Figure 5A) includes 17 studies.7,23–26,28–31,35,36,40–42,46,57,58 The total number of examined implants in the network is 2178. SUCRA values (Figure 5C) indicate that WP are likely to have the smallest bleeding on probing (SUCRA: 88.3%) followed by EC (SUCRA: 77.47%). CS, NS, ST were ranked respectively (SUCRA: 59.18%, 24.75%, 0.26%). Heat plot for bleeding on probing (Figure 5B) represents the pairwise comparisons of different nicotine-containing product users and nonsmokers. NS have statistically higher BOP than WP (MD: 16.13 CrI: 10.49, 21.7), EC (MD: 14.67 CrI: 7.82, 21.54), and CS (MD: 12.41 CrI:7.95, 16.91). ST has statistically higher BOP than WP (MD: 33.59 CrI: 18.3, 48.85), EC (MD: 32.13 CrI: 16.02, 48.32), CS (MD: 29.87 CrI: 14.82, 44.34), and NS (MD: 17.46 CrI: 2.63, 31.87). The consistency-inconsistency plot (Figure 5D) shows no remarkable heterogeneity.

Figure 5. (A) Network geometry of the eligible comparisons of bleeding on probing in different nicotine-containing product user groups and nonsmokers; (B) the league-heat diagram contains the mean difference and 95% credible interval for all possible treatment pairs, ST have statistically higher bleeding on probing (BOP) than other groups, NS have statistically higher BOP than WP, EC, CS; (C) surface under the cumulative ranking curves (SUCRA%) values of bleeding on probing, NS has the greatest likelihood of ranking first. Secondly, EC has the highest probability of reaching one of the top rankings; and (D) the consistency-inconsistency plot reveals no significant heterogeneity. CS = cigarette smokers; EC = electronic cigarette; NS = nonsmokers; ST = smokeless tobacco; WP = waterpipe.

Other Clinical and Immunological Parameters, Oral Hygiene

Results of the analysis of GI, PPD > 4 mm, modified plaque index, PISF volume, and TNF-α and IL-1β levels are presented in Supplementary Document 1 (Supplementary Figure 1.2–1.7). Oral hygiene habits of the included participants are presented in Supplementary Document 1 (Supplementary Figure 1.8).

Subset Analysis

Subset analysis was performed based on the smoking habit, implant duration, and maintenance control. The subgroup division and analysis results are detailed in Supplementary Document 3.

Certainty of Evidence

Using the CINeMA tool, the quality of evidence was found to be low. The confidence rating was low because of the observational study design; however, the use of RCTs was not possible in our meta-analysis. The evidence was also downgraded because of heterogeneity, incoherence, and reporting bias (Supplementary Document 4, Supplementary Figure 4.1–4.10).

Discussion

The findings of the current investigation support the hypothesis that smokers exhibit inferior peri-implant clinical and radiographic parameters and also higher proinflammatory cytokine profile in comparison to nonsmokers. The results of the present study are in line with the findings of the previous systematic reviews61 and meta-analyses13,15,62 that indicate the detrimental effect of nicotine-containing products on peri-implant health.

Cigarette and waterpipe smoke contains harmful chemicals, such as CO, nicotine, and tar.63 EC vapor contains toxic compounds, including nicotine, formaldehyde, acetaldehyde, and acrolein.64 Cigarette smoking and vaping are suspected to induce oxidative stress and increase the expression of advanced glycation end products (AGEs).42 Elevated levels of AGEs can stimulate the proliferation of macrophages and monocytes and increase the expression of systemic and local proinflammatory cytokines.7 TNF-α, IL-6, and IL-1β play a crucial role in accelerating peri-implant tissue destruction and alveolar bone loss around dental implants.65 Nicotine has been associated with impaired cellular healing response66 and also increased oral biofilm accumulation on titanium plates in vitro.67

Nicotine causes gingival vasoconstriction, which leads to a reduction in gingival bleeding compared to individuals who do not smoke.68 As they have fewer sites with BOP, nicotine-containing users may be unaware of the possibility of a persistent inflammatory process in the oral soft tissues.15,69 The greater rate of plaque index among cigarette and waterpipe users may be related to their disregard for oral hygiene maintenance. Smokeless tobacco users insert the product in the buccal vestibule. As a result, it has been proposed that peri-implant inflammatory parameters may be worse surrounding implants positioned in the vicinity of smokeless tobacco placement, in comparison to implants situated on the opposite side.70 Oral premalignant and malignant lesions were strongly associated with smokeless tobacco use, presumably because of the smokeless tobacco’s topical action on the oral mucosa.71

It is known that smoking and periodontal disease have a dose-dependent and dose-duration-dependent relationship.14 In our analysis, EC users did not show significant differences from NS in many outcomes; however, the differences were significant on a study level.7,29,35,42,57 Individuals with a prolonged history and greater daily frequency of smoking are more susceptible to peri-implant inflammation.72 Duration of the smoking habit and daily frequency of use were relatively shorter in EC group compared to CS. Furthermore, EC users were relatively younger, and it is known that periodontal disease severity can increase with age.13

Maintaining a good oral hygiene is a key factor to prevent plaque accumulation,73 thereby reducing the risk of peri-implant diseases.74 Only a few included studies assessed the brushing frequency of included participants (Supplementary Document 1, Supplementary Figure 1.8). NS and EC users reported similar habit of brushing their teeth twice daily, while CS brushed their teeth less frequently. Alazmi et al.33 reported that dental implants can remain functionally stable in both NS and EC when strict domestic oral hygiene measures are kept and routine dental prophylaxis is carried out.

In most studies, strict inclusion criteria were used, as well as people with systemic diseases like diabetes mellitus were left out of the studies to reduce possible confounding factors. The majority of the studies used strict criteria to define smoker groups; however, some papers lacked a precise definition of smokers45,48,55 and nonsmokers.27,44,45,47,48,54,55 Most studies relied on self-reported data regarding the smoking status and smoking history of the included participants. Alqahtani et al.35 examined the peri-implant sulcular fluid cotinine levels, while BinShabaib et al.46 assessed the salivary cotinine level of the included participants to verify their smoking status. Cotinine is a metabolite of nicotine, and it can be found in saliva and gingival crevicular fluid for a period of up to 1 week following the use of nicotine products.35 No biochemical testing was made in the rest of the articles to confirm the participants’ smoking status, which introduces uncertainty regarding their accuracy. Although current cigarette smoking was an exclusion criterion among EC, WP, and ST users, only few studies excluded participants with past smoking habit.7,26,33,46 Furthermore, some studies did not exclude former smokers from the nonsmoker group as well.56,59,60 Differences in demographics, such as gender, age, socioeconomic status, or other prognostic factors could also influence the results.14 Friedman et al.75 found that more educated smokers are more likely to switch to exclusive e-cigarette use. Good educational background is associated with favorable oral health knowledge.76 Many studies included only male participants. Females are suspected to be more prone to peri-implant soft tissue inflammation and crestal bone loss because of hormonal imbalances.28 It should also be noted that majority of the studies included in this analysis were carried out in the Middle East. Cultural or racial traits specific to this region may have an impact on the clinical results, hence limiting the generalizability of the findings.

Strengths and Limitations

Regarding the strengths of our analysis, we followed our preregistered protocol, performed both univariate and multivariate analyses to achieve objectivity, and employed rigorous methodology. Furthermore, this was the first systematic review and NMA investigating the peri-implant status of users of four types of nicotine-containing products and nonsmokers. We conducted a comprehensive evaluation of various outcomes and were able to establish direct comparisons among most of the products.

Some limitations of this meta-analysis must be acknowledged. First, we included observational studies, as RCTs on this topic cannot be conducted. The articles employed various screening methodologies for PPD, gingival, and plaque indices. Thus, concerning certain outcomes, only a limited number of studies could be included. This resulted in an incomplete network geometry, which prevented a high-quality statistical evaluation. Heterogeneity in patient characteristics could also be a limitation. Insufficient reporting of confounders was observed in certain articles. Including only English-language studies is another limitation regarding the high rates of nicotine-containing product use in non-English-speaking regions (South Asian, Middle Eastern countries, etc.).

Implication for Practice

The findings gathered from this review may serve as an informative tool for healthcare professionals that any kind of nicotine-containing product might have a negative impact on peri-implant health. It is essential to address the misconception that smokeless tobacco and waterpipe is safer to use than conventional cigarettes. Electronic cigarette smokers presented comparable peri-implant parameters to nonsmokers, thus might be considered a less harmful alternative to cigarette smoking; however, they are not entirely harmless. Patients should be provided with information indicating that the use of any nicotine-containing product carries potential risks of adverse effects on dental implants, with an emphasis on the benefits of quitting smoking.

Implication for Research

The adoption of novel scientific findings is crucial for community dentistry.77,78 Well-designed, multiarmed studies are needed for direct comparison of different products. Future studies should include heated tobacco products since there is no available literature concerning them. Greater transparency of confounding factors is needed regarding smoking habit and oral hygiene. In addition, we recommend measuring various periodontal parameters according to the standard protocol so that studies can be compared in future meta-analyses.

Conclusion

Most nicotine-containing product users presented worse clinico-radiographic and immunological peri-implant parameters compared to NS. EC users did not show significant differences to NS in many outcomes.

Supplementary Material

Supplementary material is available at Nicotine and Tobacco Research online.

ntae085_suppl_Supplementary_Data_S1

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ntae085_suppl_Supplementary_Table_S1

Funding

Funding was provided by the Centre for Translational Medicine, Semmelweis University. Sponsors had no role in the design, data collection, analysis, interpretation, and manuscript preparation.

Declaration of Interests

The authors claim that the study was carried out without any commercial or financial associations that could be interpreted as a possible source of conflict of interest.

Author Contributions

Orsolya Vámos (Conceptualization [equal], Data curation [lead], Formal analysis [supporting], Investigation [lead], Methodology [equal], Visualization [equal], Writing—original draft [lead]), Péter Komora (Data curation [equal], Investigation [lead], Writing—review & editing [supporting]), Noémi Gede (Formal analysis [lead], Writing—review & editing [supporting]), Péter Hegyi (Conceptualization [equal], Methodology [lead], Supervision [lead], Writing—review & editing [equal]), Kata Kelemen (Conceptualization [equal], Methodology [lead], Project administration [equal], Supervision [equal], Writing—review & editing [equal]), Gábor Varga (Supervision [equal], Writing—review & editing [equal]), Krisztina Mikulás (Writing—review & editing [equal]), Beáta Kerémi (Writing—review & editing [equal]), and Ida Barbara Kispelyi (Conceptualization [equal], Data curation [supporting], Methodology [equal], Project administration [equal], Supervision [lead], Writing—review & editing [lead])

Ethical Approval

No ethical approval was required for this systematic review with meta-analysis, as all data were already published in peer-reviewed journals. No patients were involved in the design, conduct, or interpretation of our study.

Data Availability

The data sets used in this study can be found in the full-text articles included in the systematic review and meta-analysis.
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