The Impact of Cigarette Smoking, Waterpipe Smoking, and E-Cigarette Vaping on Peri-Implant Clinical Outcomes and Inflammatory Markers: a Systematic Review and Meta-Analysis

Objectives: The purpose of this systematic review and meta-analysis was to evaluate and compare the impact of cigarette smoking, waterpipe smoking, and electronic cigarette vaping on peri-implant clinical outcomes and inflammatory biomarkers in comparison with non-smokers.

Material and Methods: The systematic review was conducted following PRISMA guidelines. A comprehensive literature search was performed using the MEDLINE (PubMed) database. Studies published between October 2015 and October 2025 involving adults with dental implants were included. Random-effects models calculated mean differences (MD) for marginal bone loss and cytokines, and standardized mean differences (SMD) for plaque index and bleeding on probing (BOP).

Results: All smoking modalities were associated with significantly worse peri-implant outcomes than non-smokers. Plaque index increased for cigarette (+5.22 units), waterpipe (+6.31), and e-cigarette users (+1.61). Marginal bone loss was greater in cigarette (+2.16 mm), waterpipe (+1.9 mm), and e-cigarette users (+0.83 mm). Cigarette smokers showed the highest IL-1β (MD = 239.63 pg/mL), while e-cigarette users exhibited elevated IL-1β (+170 pg/mL) and TNF-α (+17.6 pg/mL). A paradoxical reduction in BOP was observed. Subgroup analyses confirmed a risk gradient of cigarette > waterpipe > e-cigarette > non-smoker.

Conclusions: Cigarette smoking exerts the greatest detrimental effect on peri-implant outcomes, followed by waterpipe and e-cigarette use. All modalities promote bone loss, plaque accumulation, and inflammation despite reduced bleeding, likely due to nicotine-induced vasoconstriction. Evidence on waterpipe and vaping remains limited, emphasizing the need for standardized long-term studies.

J Oral Maxillofac Res 2025;16(4):e1

doi: 10.5037/jomr.2025.16401

Accepted for publication: 18 December 2025

Keywords: biomarkers; cigarette smoking; dental implants; electronic nicotine delivery systems; vaping; waterpipe smoking.

INTRODUCTION

Dental implants have become a widely accepted and effective treatment modality for replacing missing teeth, offering high long-term success rates and improved quality of life for patients [1]. Since their clinical introduction in the 1960s by Per-Ingvar Brånemark, dental implants have undergone significant evolution and are now routinely used in modern dentistry [2]. However, like natural teeth, implants are subject to biological and environmental challenges that may compromise their stability and longevity [3,4]. Among the various risk factors that affect peri-implant health, smoking and nicotine exposure have been consistently associated with adverse clinical outcomes. This has prompted increasing interest in exploring how different forms of nicotine consumption impact the peri-implant tissues and whether other types of smoking affect the peri-implant soft and hard tissues differently [5].

Historically, conventional cigarette smoking has been the most studied in relation to oral health and implant complications. In recent years, there has been a growing shift toward alternative forms of nicotine consumption, including e-cigarettes, heated tobacco, smokeless tobacco, and waterpipes, which have become increasingly prevalent, especially among middle school and high school students [6,7]. These products are often perceived as less harmful than traditional cigarettes, but their biological effects on oral and peri-implant tissues remain unclear [8].

Among these alternatives, electronic nicotine delivery systems (ENDS), such as e-cigarettes, have garnered particular attention. According to the 2018 National Youth Tobacco Survey [9], e-cigarette use increased sharply among U.S. students, by 78% in high schoolers and 48% in middle schoolers, despite legal prohibitions on sales to minors. Despite being marketed as safer alternatives, studies have identified harmful substances in their vapour, including heavy metals like aluminium, arsenic, and nickel, which may affect soft and hard tissues around implants [10,11].

Waterpipe smoking, a practice with cultural roots in the Middle East and South Asia, has also gained global popularity. While users often believe that the water filters out harmful substances, research shows that toxic components still reach the oral cavity and respiratory system, potentially compromising peri-implant health [12-14]. Despite the growing prevalence of these non-combustible and alternative nicotine delivery methods, their specific effects on peri-implant tissues have not been well characterized in the literature. Considering the differences in their composition, frequency of use, and exposure patterns, it is essential to examine whether these products pose similar or unique risks compared to conventional smoking [15,16]. Therefore, this review aims to evaluate the current evidence on the impact of various nicotine consumption methods - including cigarettes, waterpipes, and electronic nicotine delivery systems - on peri-implant health, assessed through clinical and radiographic outcomes. Two objectives were defined:

1. Compare peri-implant clinical parameters - bleeding on probing, probing depth, plaque index, and marginal bone loss among adult dental implant patients who are cigarette smokers, waterpipe smokers, e-cigarette users, and non-smokers.

2. Evaluate and compare the levels of inflammatory biomarkers (interleukin-1β, tumour necrosis factor-α) in peri-implant sulcular fluid among cigarette smokers, waterpipe smokers, e-cigarette users, and non-smokers.

MATERIAL AND METHODS

Protocol and registration

This review was conducted in accordance with the PRISMA guidelines [17] and was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) under the identifier CRD420251137108, accessible at https://www.crd.york.ac.uk/PROSPERO/.

Focus question

The focus question was formulated using the Patient, Intervention, Comparison, and Outcome (PICO) framework (Table 1): “Among adults with dental implants, which form of smoking, cigarettes, e-cigarettes, or waterpipe, has the most detrimental effect on peri-implant clinical parameters and inflammatory biomarker levels compared to non-smokers?”

Information sources

A comprehensive search was conducted in MEDLINE (PubMed), supplemented by a manual search of reference lists of relevant studies.

Search strategy

The search was conducted in stages: database retrieval using predefined terms. The search covered studies published between October 1, 2015, and October 1, 2025. The combinations of MeSH terms and free-text keywords were used as presented in Table 2.

Selection of studies

Screening and study selection were conducted by two reviewers (L.B. and I.L.) using the online screening tool Rayyan^® (Qatar Computing Research Institute; HBKU, Doha, Qatar [www.rayyan.ai]). Duplicate records were removed, followed by title and abstract screening. The remaining articles were then retrieved for full-text evaluation according to the inclusion and exclusion criteria, resulting in the final selection of eligible studies. In cases of disagreement between the reviewers, the senior researcher (G.J.) was consulted. The level of agreement between the two authors (L.B. and I.L.) in selecting abstracts and studies to be read in full-text was tested using the Cohen´s kappa coefficient (κ). Reasons for exclusion at the full-text stage were documented and summarized in a PRISMA flow diagram.

Types of publications

Only refereed scientific publications in peer-reviewed journals, including original articles, were considered. Literature reviews, systematic reviews, meta-analyses, case reports, editorials, conference abstracts, theses, and non-refereed publications were excluded.

Types of studies

Eligible studies included randomized controlled trials, prospective and retrospective cohort studies, and cross-sectional studies, provided that each study included a minimum of 10 patients.

Types of participants

The review included adult patients (≥ 18 years) with at least one functional dental implant. Participants were categorized as cigarette smokers, waterpipe smokers, electronic cigarette users, or non-smokers (controls).

Inclusion criteria

• Studies involving adult patients with dental implants.

• Studies published between October 2015 and October 2025.

• Full text available.

• Studies written in English.

• Randomized controlled trials, cross-sectional studies, case-control studies, case series, and cohort studies.

• Minimum 10 patients in the study.

• Studies including test groups of cigarette smokers and/or waterpipe smokers and/or e-cigarette users, and non-smokers as controls.

Exclusion criteria

• Systematic review.

• Literature review.

• Studies conducted on species other than humans.

• Animal studies, in vitro studies, or cadaveric studies.

• Case reports, editorials, or conference abstracts.

Sequential search strategy

Initial electronic database search, application of inclusion and exclusion criteria, full-text screening of potentially eligible studies, final selection of articles for qualitative and quantitative analysis.

Data extraction

The first reviewer (L.B.) independently extracted relevant information from studies, based on the objectives and tasks of this study. A second reviewer (I.L.) then verified the extracted data for accuracy and consistency before compiling it into a final dataset. Discrepancies were resolved through discussion or the intervention of senior investigator (G.J.) to reconcile the inconsistency.

Data items

The following items were extracted: first author, publication year, follow-up, study design, intervention group, number of patients in each group, mean age (or range), duration of the longest follow-up (years) presented in the article, habit duration (years), daily frequency (in minutes), duration of each session (in minutes), brushing (once/twice, %), number of implants, implant duration, plaque index (%), probing depth (PD) > 4 mm (%)/mm, bleeding on probing (BOP, %), marginal bone loss (MBL, mm), and inflammatory biomarkers: interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α).

Risk of bias within the studies

Two research authors (L.B and I.L) conducted a formal risk of bias evaluation using the Joanna Briggs Institute (JBI) Critical Appraisal Checklists for analytical cross-sectional studies (Table 3), case-control studies (Table 4), and cohort studies (Table 5).

Studies with ≤ 49% positive responses were classified as having a high risk of bias, those with 50 to 69% as moderate risk, and those with ≥ 70% as low risk.

Statistical analysis

Numerical values are presented as mean and standard deviation (M [SD]). The level of P-value was set considerably statistically significant at < 0.05.

Meta-analyses were performed in RStudio version 2025.05.0-496 (Posit PBC; Boston, Massachusetts, USA) using the meta package. A random-effects model with restricted maximum likelihood (REML) estimation was used to account for between-study heterogeneity. Mean differences (MD) with 95% confidence intervals (CIs) and prediction intervals (PIs) were calculated. For outcomes reported on different scales (e.g., plaque index, BOP), standardized mean differences (SMDs) were used. Forest plots were generated to display pooled effect sizes, and funnel plots were used for visual inspection of potential small-study effects. Because fewer than 10 studies contributed to each analysis, Egger’s regression was not performed, as it is considered unreliable under these conditions.

Additional analysis

Subgroup analyses were conducted to compare different smoking habits (cigarette vs waterpipe, cigarette vs e-cigarette, and waterpipe vs e-cigarette) across clinical and inflammatory outcomes.

RESULTS

Study selection

A total of 255 records were identified. After removing 2 duplicates, 253 records remained for screening. A total of 205 were excluded at titles and abstracts screening stage. Forty-eight full-text articles were assessed for eligibility. Finally, nine studies were included (Figure 1). The level of agreement between the two authors (L.B. and I.L.) in selecting abstracts and studies to be read in full-text were measured at κ = 0.9 and κ = 1.0, indicating perfect reliability of agreement.

Exclusion of studies

After full-text review, thirty-nine studies were excluded: thirty-seven for not meeting inclusion criteria [18-54], one was a non-English article [55], and one was a retracted article [56].

Risk of bias assessment

Using the JBI Critical Appraisal Checklists, the studies included in the present study demonstrated a low risk of bias. Five [57-61] of nine studies rated low risk of bias, while four [62-65] studies were of moderate risk of bias (Tables 6, 7 and 8).

Study characteristics

This review included nine studies published between 2018 and 2023 [57-65]. Most were cross-sectional (n = 6) [57-62], with two case-control studies [63,64] and one retrospective cohort study with an 8-year follow-up [65]. All studies included a never-smoker comparison group and evaluated at least one smoking exposure group, including cigarette smokers [57,58,60,62,63], vape smokers [57-61,65], and/or waterpipe smokers [58,60,62-64]. Sample sizes were generally comparable between groups within each study, with group sizes ranging from 19 to 64 participants. As summarized in Table 9, several studies reported smoking-related exposure characteristics, including habit duration, daily frequency, and session duration, as well as oral hygiene behavior (brushing frequency). Implant-related characteristics were also reported, including the number of implants per group (where available) and implant functional duration, which was presented in months or years depending on the study.

Outcomes of the included studies

Inflammatory biomarkers

Inflammatory biomarker outcomes are summarized in Table 10. For IL-1β, all studies reporting this outcome showed higher concentrations in smokers than in non-smokers. Cigarette smokers consistently had markedly elevated IL-1β compared with non-smokers, with significant differences in both [57] (246.53 [SD 115.2] vs 36.91 [SD 22.3] pg/mL) and [58] (281.4 [SD 13.2] vs 19.7 [SD 22.3] pg/mL; P < 0.01 to P < 0.001). Vape smokers also showed significantly higher IL-1β than non-smokers in studies reporting vape smokers, with reported means around 196 to 205 pg/mL (significant across studies; P values as shown in Table 10) [57-59,61]. Waterpipe smokers likewise demonstrated elevated IL-1β where reported, including 272.6 (SD 15.9) pg/mL in [58], significantly higher than non-smokers (P < 0.01).

For TNF-α, fewer studies reported data. In the study of AlQahtani et al. [58], cigarette smokers had substantially higher TNF-α than non-smokers (109.2 [SD 20.5] vs 6.7 [SD 8.1] pg/mL; P < 0.01), and waterpipe smokers was similarly high (105.6 [SD 22.7] pg/mL). Vape smokers also showed higher TNF-α than non-smokers in the studies reporting this comparison, with a reported mean of 24.3 (SD 32.4) pg/mL and statistically significant differences (P < 0.01 or P < 0.001) [58,59,61]. TNF-α was not reported in the remaining studies (Table 10).

Plaque index

In the included studies, plaque accumulation was assessed using two main approaches. Several studies recorded plaque dichotomously (present/absent) at six sites per implant and reported the percentage of implant sites exhibiting visible plaque (%). Other studies assessed plaque using ordinal plaque indices scored on a 0 - 3 scale (such as the Löe plaque index or a modified peri-implant) were reported either as the percentage of implant sites with visible plaque or as an ordinal Silness and Löe plaque score (0 - 3). Plaque index outcomes are presented in Table 11.

Across studies reporting plaque as a percentage, cigarette smokers had significantly higher plaque levels than non-smokers, with cigarette smokers typically around 56 to 67% versus about 30 to 39% in non-smokers (P < 0.05 to P < 0.01) [57,58,63]. Waterpipe smokers also showed higher plaque percentages than non-smokers (significant in the studies reporting waterpipe smokers) [58,63]. Vape smokers demonstrated intermediate plaque accumulation, but still significantly higher than non-smokers in the studies reporting vape smokers [57,58]. In studies using the 0 - 3 ordinal plaque index, non-smokers showed markedly lower plaque scores than cigarette smokers and waterpipe smokers [62] (P < 0.01), while Alazmi et al. [65] reported no significant differences between groups (P > 0.05).

Probing depth

PD is a linear measurement expressed in millimetres (mm). However, PD ≥ 4 mm is commonly used as a threshold to indicate the proportion of sites with pathologic pocketing. Therefore it was reported either as the percentage of sites with PD > 4 mm or as mean PD in mm. PD outcomes are presented in Table 11.

In studies reporting PD as a percentage and including a non-smoker comparator, cigarette smokers consistently showed a higher proportion of sites with PD > 4 mm than non-smokers (cigarette smokers: 4.3 [SD 0.2]% to 23.8 [SD 2.7]% vs non-smokers: 0.8 [SD 0.1]% to 5.1 [SD 0.2]%; P < 0.01 or P < 0.05) [57,58,60,63]. Waterpipe smokers also demonstrated higher PD > 4 mm percentages than non-smokers in the studies reporting waterpipe smokers (P < 0.01 or P < 0.05) [58,60,63,64]. Similarly, vape smokers showed higher PD > 4 mm percentages than non-smokers across the studies reporting vape smokers (vape smokers: 3.2 [SD 0.3]% to 15.9 [SD 1.4]%; P < 0.01 or P < 0.05) [57-61]. For studies reporting mean PD (mm), Ali et al. [62] found higher mean PD in smokers than controls (cigarette smokers: 4.7 [SD 0.4] mm and waterpipe smokers: 4.5 [SD 0.4] mm vs control: 1.7 [SD 0.2] mm; P < 0.01), whereas Alazmi et al. [65] reported no significant difference between vape smokers and non-smokers (vape smokers: 1.8 [SD 0.1] mm vs non-smokers: 1.6 [SD 0.03] mm; P > 0.05).

Bleeding on probing

BOP is presented in Table 11 as the percentage of sites that bleed after probing. Across studies with a non-smokers comparator, cigarette smokers consistently showed significantly lower BOP than non-smokers (cigarette smokers: 6.8 [SD 1.2]% to 18.4 [SD 4.8]% vs non-smokers: 19.8 [SD 1.3]% to 41.5 [SD 2.7]%; P < 0.01 or P < 0.05) [57,58,60,63]. Waterpipe smokers also demonstrated significantly lower BOP than non-smokers in the studies reporting waterpipe smokers (waterpipe smokers: 7.9 [SD 1.8]% to 20.4 [SD 2.4]% vs non-smokers: 19.8 [SD 1.3]% to 41.5 [SD 2.7]%; P < 0.01 or P < 0.05) [58,60,63,64]. Similarly, vape smokers had lower BOP than non-smokers across the studies reporting vape smokers (vape smokers: 6.6 [SD 1.3]% to 24.7 [SD 5.3]% vs non-smokers: 19.8 [SD 1.3]% to 39.8 [SD 18.1]%; P < 0.01 or P < 0.05) [57-61]. BOP was not reported in two studies [62, 65].

Marginal bone loss

MBL is reported in Table 11 in mm as mean (SD). Some studies report a single mean MBL, while others report mesial and distal values. Across all studies that compared cigarette smokers with non-smokers, cigarette smokers consistently had higher MBL, with statistically significant differences (P < 0.01) [57,58,62] and (P < 0.05) [63]. Vape smokers generally showed higher MBL than non-smokers (significant differences) [57,59,61], while no significant differences were found in vape smokers vs non-smokers for either mesial or distal MBL [65]. Waterpipe smokers also showed higher MBL than non-smokers in studies reporting waterpipe smokers (P < 0.01) [62], (P < 0.05) [63], and (P < 0.05) [64].

Meta-analysis

Cigarette smokers vs non-smokers

Clinical outcomes and inflammatory biomarkers were compared between cigarette smokers and non-smokers. A significant reduction in BOP (SMD = -6.67; 95% CI = -9.7 to -3.64; PI = -17.46 to 9.1) was observed in smokers (Figure 2). In contrast, plaque index was significantly higher in smokers, with a pooled increase of 5.22 units (95% CI = 2.69 to 7.75) (Figure 3). Marginal bone loss was also greater, with smokers showing an average increase of 2.16 mm compared with non-smokers, although heterogeneity was high (τ² = 0.39, I² = 94%) (Figure 4). Moreover, IL-1β levels were markedly elevated among smokers (MD = 239.63; 95% CI = 189.19 to 290.07; PI = -298.69 to 777.95; τ² = 1132.64; I² = 83.5%) (Figure 5). There were insufficient studies to perform a meta-analysis for TNF-α.

Waterpipe smokers vs non-smokers

The results of subgroup meta-analysis comparing clinical outcomes between waterpipe smokers and non-smokers are presented in Figures 6, 7 and 8. Bleeding on probing was significantly reduced in waterpipe smokers (SMD = -5.99; 95% CI = -8.37 to -3.61; PI = -14.37 to 2.39; τ² = 5.46; I² = 95.5%) (Figure 6). In contrast, plaque index was substantially higher, with a pooled increase of 6.31 units (95% CI = 2.38 to 10.24; PI = -7.16 to 19.78; τ² = 19.5; I² = 96.2%) (Figure 7). Marginal bone loss was also significantly greater in waterpipe smokers, with a mean increase of 1.9 mm compared with non-smokers (95% CI = 1.11 to 2.68; PI = -6.82 to 10.61; τ² = 0.31; I² = 97%) (Figure 8). There were insufficient studies to evaluate TNF-α or Interleukin-1β outcomes in this subgroup.

Vape smokers vs non-smokers

Figures 9, 10, 11, 12 and 13 present the results of the subgroup analysis comparing outcomes between vape smokers and non-smokers. Bleeding on probing (BOP) was significantly reduced in vape smokers (SMD = -4.76; 95% CI = -7.66 to -1.87; PI = -14.7 to 5.17).

Plaque index was significantly higher in vape smokers (SMD = 1.61; 95% CI = 1 to 4.21; PI = -7.38 to 10.59), confirming increased plaque accumulation compared to non-smokers (Figure 10).

MBL was also modestly but significantly greater in vape smokers, with a mean difference of 0.83 mm (95% CI = 0.32 to 1.33; τ² = 0.015; I² = 43.6%) (Figure 11).

Inflammatory biomarkers consistently showed significant elevations: TNF-α was higher by 17.6 units (95% CI = 11.9 to 23.3; τ² = 0; I² = 0.0%), and IL-1β was elevated by 170 units (95% CI = 144.9 to 195.3; PI = 129.19 to 211.05; τ² = 0; I² = 0.0%) (Figure 12 and 13).

Additional analysis

Subgroup analysis was conducted among cigarette vs waterpipe smokers, cigarette vs e-cigarette smokers, and waterpipe vs e-cigarette smokers.

Cigarette vs waterpipe smokers

For BOP, the pooled model showed no statistically significant difference between cigarette and waterpipe smokers (SMD = -0.27; 95% CI = -0.53 to -0.01), with very high heterogeneity (I² = 97.4%) (Figure 14).

For plaque index, the analysis revealed a statistically significant difference, with cigarette smokers demonstrating higher values compared with waterpipe smokers (SMD = 0.4; 95% CI = 0.16 to 0.63), although heterogeneity remained substantial (I² = 96%) (Figure 15).

For MBL, the pooled model favoured cigarette smokers, who exhibited significantly greater bone loss than waterpipe smokers (MD = 0.26 mm; 95% CI = 0.12 to 0.4), with very high heterogeneity (I² = 99.9%) (Figure 16).

For IL-1β, heterogeneity was moderate (I² = 64.5%), and the pooled random-effects model showed no statistically significant difference between cigarette and waterpipe smokers (MD = -2.75 pg/mL; 95% CI = -34.92 to 29.42) (Figure 17).

Cigarette and e-cigarette smokers

For BOP, the pooled model showed no statistically significant difference between cigarette and e-cigarette smokers (SMD = -0.19; 95% CI = -1.45 to 1.08), with very high heterogeneity (I² = 94.9%) (Figure 18). For plaque index, cigarette smokers exhibited significantly higher values compared with e-cigarette users (SMD = 2.13; 95% CI = 0.83 to 3.43), although heterogeneity was also substantial (I² = 91.1%) (Figure 19). For MBL, the pooled effect favoured cigarette smokers, who showed significantly greater bone loss than e-cigarette users (MD = 1.33 mm; 95% CI = 0.55 to 2.11), with high heterogeneity (I² = 84.7%) (Figure 20).

For IL-1β, heterogeneity was absent (I² = 0.0%), and cigarette smokers had significantly higher levels compared with e-cigarette users (MD = 59.05 pg/mL; 95% CI = 17.43 to 100.66) (Figure 21).

Taken together, these findings indicate that cigarette smoking is associated with greater peri-implant plaque accumulation, MBL, and IL-1β upregulation compared with e-cigarette use, whereas differences in BOP remain inconclusive due to high variability across studies.

E-cigarette smokers vs waterpipe smokers

For BOP, the pooled model did not show a statistically significant difference between e-cigarette and waterpipe smokers (SMD = -0.2; 95% CI = -2.18 to 1.79), with very high heterogeneity (I² = 97%) (Figure 22).

For plaque index, the pooled analysis indicated a statistically significant difference, with waterpipe smokers demonstrating higher plaque accumulation compared with e-cigarette users (SMD = 2.05; 95% CI = 0.62 to 3.47). However, heterogeneity was also high (I² = 91.4%) (Figure 23).

Taken together, these findings suggest that waterpipe smoking may be associated with greater plaque accumulation than e-cigarette use, while differences in BOP remain inconclusive due to substantial heterogeneity and limited available data.

DISCUSSION

This study compared the effects of cigarette smoking, waterpipe smoking, and e-cigarette use on peri-implant clinical parameters and inflammatory biomarkers, with non-smokers serving as controls. Across all modalities, all types of smoking were consistently associated with worse peri-implant outcomes. Smokers exhibited significantly higher plaque index and greater MBL, as well as elevated pro-inflammatory biomarkers (IL-1β and TNF-α) compared to non-smokers. Increased PD (PD > 4 mm (%)/mm) was also reported in several included studies, although this parameter was not pooled in the meta-analysis. These finding are in line with Dreyer et al. [66] who found that smoking was significantly associated with an increased risk of peri-implantitis, with smokers having 1.7 times higher odds compared to non-smokers.

A paradoxical but consistent finding across all smoking modalities was the reduction in BOP. Cigarette smokers (SMD = -6.67; 95% CI = -9.7 to -3.64; PI = -17.46 to 9.1), waterpipe smokers (SMD = -5.99; 95% CI = -8.37 to -3.61; PI = -14.37 to 2.39), and e-cigarette users (SMD = -4.76; 95% CI = -7.66 to -1.87; PI = -14.67 to 5.17) all showed lower BOP than controls, with the greatest reduction observed in cigarette smokers, followed by waterpipe smokers, and the least reduction in e-cigarette users. This paradoxical finding aligns with de Souza et al. [67] who reported that smokers had 2.9 times fewer sites with BOP compared to non-smokers. More recently, Amerio et al. [68] confirmed this effect, reporting that smokers had significantly less peri-implant BOP than non-smokers (OR = 0.356; 95% CI = 0.193 to 0.66), suggesting that smoking reduces the diagnostic sensitivity of BOP for peri-implant inflammation.

The underlying cause of this phenomenon is explained by Scott and Singer [69] who noted that tobacco smoke masks gingival inflammation because nicotine constricts blood vessels, suppresses the formation of new microvessels during inflammatory responses, and alters inflammatory mediator activity. Supporting this, Sharma et al. [70] emphasized that nicotine-induced vasoconstriction reduces gingival blood flow and, together with heavier keratinization of the gingiva in smokers, diminishes visible bleeding despite ongoing inflammation.

For plaque index, cigarette smokers (+5.22 units; 95% CI = 2.69 to 7.75) and waterpipe smokers (+6.31 units; 95% CI = 2.38 to 10.24) exhibited the greatest increases, while e-cigarette users also showed significantly higher plaque accumulation (+1.61 units; 95% CI = 1 to 2.21) compared to non-smokers, though still less than cigarette and waterpipe users. These findings are consistent with an impaired oral environment favouring biofilm accumulation, a pattern also observed by Mokeem et al. [71] who reported significantly higher plaque scores in cigarette and waterpipe smokers compared with e-cigarette users and never-smokers.

MBL was consistently greater across modalities. Cigarette smokers exhibited the greatest bone loss (+2.16 mm; I² = 94%), followed by waterpipe smokers (+1.9 mm; I² = 97%), while e-cigarette users (+0.83 mm; I² = 43.6%) showed the least but still significant increase compared with non-smokers. However, the extreme heterogeneity for combustion-based products indicates that these pooled averages are not reliable predictors for individual patients, as study outcomes varied widely. The broad prediction intervals (e.g., -6.82 to 10.61 mm for waterpipes) reinforce this uncertainty. By contrast, the moderate heterogeneity for e-cigarettes suggests a more consistent and predictable biological effect. These findings are in agreement with Peñarrocha et al. [72] who reported significantly greater MBL in smokers compared to non-smokers, supporting the detrimental role of tobacco use in peri-implant bone stability. Similarly, Afshari et al. [73] demonstrated a clear dose-response relationship, with patients smoking more than 10 cigarettes per day experiencing significantly greater MBL than both lighter smokers and non-smokers, indicating that the severity of smoking exposure amplifies peri-implant bone loss.

Regarding inflammatory biomarkers, IL-1β and TNF-α are key pro-inflammatory cytokines in peri-implant tissue breakdown. Both stimulate osteoclast differentiation and bone resorption, and serve as early biochemical markers of peri-implant inflammation when detected in peri-implant crevicular fluid [74,75].

In this review, only four [58,60,64,65] studies reported on inflammatory biomarkers, all of which assessed peri-implant sulcular fluid. Among the smoking modalities, only cigarette smokers and e-cigarette users were evaluated, while data on waterpipe smokers were insufficient for quantitative analysis. Cigarette smokers showed the greatest increase in IL-1β (MD = 239.63 pg/mL; I² = 83.5%). Among e-cigarette users, both IL-1β (+170 units) and TNF-α (+17.6 units) were significantly elevated compared with controls, with I² = 0% for both markers, indicating very high consistency across studies. These findings are aligned with Ryder et al. [76], who demonstrated that smokers’ mononuclear cells secreted significantly higher IL-1β than those of non-smokers, whereas TNF-α levels were paradoxically higher in non-smokers, highlighting the complex and sometimes divergent cytokine responses to tobacco exposure. In comparison, Kamal and Shams [77] reported that both cigarette smokers and e-cigarette users exhibited elevated salivary IL-1β levels compared with non-smokers, with cigarette smokers showing significantly higher concentrations of both biomarkers than e-cigarette users. This indicates that while vaping induces measurable inflammation, conventional smoking exerts a stronger pro-inflammatory and pro-oncogenic effect.

A recent network meta-analysis by Vámos et al. [78] also compared cigarette, waterpipe, e-cigarette, and smokeless tobacco users with non-smokers, reporting overall detrimental effects of combustion-based products. However, their findings regarding e-cigarettes were less consistent, with no significant differences from non-smokers across several clinical parameters. In contrast, the present analysis identified significant increases in plaque accumulation and inflammatory biomarkers among e-cigarette users, suggesting that vaping may carry a measurable inflammatory burden.

Head-to-head subgroup analyses provided additional insights into the relative risk hierarchy among smoking modalities. When comparing cigarette smokers with e-cigarette users, cigarette smokers exhibited significantly greater MBL (MD = 1.33 mm; 95% CI = 0.55 to 2.11; I² = 84.7%) and higher IL-1β levels (MD = 59.05 pg/mL; 95% CI = 17.43 to 100.66; I² = 0%). Cigarette smokers also demonstrated significantly higher plaque scores (SMD = 2.13; 95% CI = 0.83 to 3.43; I² = 91.1%), while differences in BOP were not statistically significant (SMD = -0.19; 95% CI = -1.45 to 1.08; I² = 94.9%).

Comparisons between cigarette and waterpipe smokers revealed meaningful differences across outcomes. For BOP, cigarette smokers showed significantly lower bleeding than waterpipe smokers (SMD = -0.27; 95% CI = -0.53 to -0.01), although heterogeneity was very high (I² = 97.4%). Plaque index was also significantly higher in cigarette smokers compared with waterpipe smokers (SMD = 0.4; 95% CI = 0.16 to 0.63; I² = 96%), indicating greater biofilm accumulation in conventional tobacco users. Similarly, cigarette smokers exhibited significantly greater marginal bone loss than waterpipe smokers (MD = 0.26 mm; 95% CI = 0.12 to 0.40; I² = 99.9%). In contrast, no statistically significant difference in IL-1β was observed between the two groups (MD = -2.75 pg/mL; 95% CI = -34.92 to 29.42; I² = 64.5%).

Finally, waterpipe smokers exhibited significantly higher plaque index than e-cigarette users (SMD = 2.05; 95% CI = 0.62 to 3.47; I² = 91.4%), whereas BOP differences between these groups were not statistically significant (SMD = -0.2; 95% CI = -2.18 to 1.79; I² = 97%).

Taken together, these subgroup analyses reinforce the overall risk gradient of cigarette > waterpipe > e-cigarette > non-smoker. All nicotine exposures were harmful to peri-implant tissues, but the variability of combustion-based products contrasts with the striking consistency of inflammatory responses to e-cigarette use. Clinicians should be cautious not to interpret reduced BOP as a sign of health in nicotine users, and should instead rely on PD, radiographic bone loss, and biomarker data where available. Future research should prioritize prospective cohort and randomized designs, with standardized exposure measures, to better define both the magnitude and the mechanisms of risk.

Limitations

This review is limited by the number of eligible studies, with only four reporting biomarker data and insufficient evidence for waterpipe smokers. Most included studies were cross-sectional, restricting causal inference. Considerable heterogeneity was observed for combustion-based products, reflecting differences in exposure definitions, smoking intensity, and outcome measurement protocols across studies. Several studies did not adequately control for confounding factors such as oral hygiene and systemic health, which may have influenced peri-implant outcomes. At the review level, only English-language studies were included, and the small sample size precluded formal assessment of publication bias.

CONCLUSIONS

This systematic review and meta-analysis shows that cigarette, waterpipe, and e-cigarette use are all associated with significantly worse peri-implant clinical outcomes compared with non-smokers. Cigarette smoking exerts the greatest detrimental effect, with significantly higher plaque accumulation, probing depth, marginal bone loss, and IL-1β elevations. Waterpipe smokers also demonstrated significantly greater plaque and bone loss, though biomarker evidence was less consistent. E-cigarette users presented a measurable inflammatory burden, with significant increases in plaque, IL-1β, and TNF-α, despite smaller effects on bone loss.

All smoking groups showed a paradoxical reduction in BOP, reflecting nicotine-induced vasoconstriction rather than tissue health. Overall, the risk hierarchy was confirmed as cigarette > waterpipe > e-cigarette > non-smoker, with nicotine exposure in any form promoting peri-implant inflammation. Well-designed, long-term studies with standardized exposure definitions are needed to confirm both the magnitude and mechanisms of risk.

ACKNOWLEDGMENTS AND DISCLOSURE STATEMENTS

The authors declare no conflicts of interest related to this study. The authors alone are responsible for the content and writing of the paper. No financial or personal relationships influenced the outcomes of this research.

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