Search Results (1,050)

Background/Objectives: Metabolic syndrome (MetS), defined by abdominal obesity, dysglycemia, dyslipidemia, hypertension, and insulin resistance, markedly increases the risk of type 2 diabetes mellitus and cardiovascular disease. Affecting an estimated 25–30% of the global adult population, MetS represents a major and growing public health challenge. A growing body of evidence supports a significant bidirectional relationship between MetS and oral health, particularly periodontitis. The present study aimed to synthesize current evidence on the pathophysiological mechanisms, epidemiological associations, interventional outcomes, and clinical implications of the bidirectional relationship between metabolic syndrome (MetS) and periodontitis. Methods: A narrative review following the SANRA framework was performed. PubMed, Scopus, and Web of Science were searched for articles published in January 2021–March 2026 using MeSH and free-text terms including “metabolic syndrome”, “periodontal disease”, “insulin resistance”, and “oral microbiota”. Eligible studies included original research and systematic reviews in English with full-text availability; animal and in vitro studies were included if directly informative of mechanistic pathways. Results: A total of 64 references were selected for inclusion. Shared mechanisms include chronic systemic inflammation, insulin resistance, oxidative stress, adipokine imbalance, endothelial dysfunction, and oral–gut microbiome dysbiosis. Cross-sectional and longitudinal studies show that MetS components are independently associated with higher prevalence and severity of periodontitis; meta-analyses report pooled odds ratios of 1.7–1.9 compared with metabolically healthy controls. Non-surgical periodontal therapy produces modest but significant reductions in glycated hemoglobin (HbA1c) and systemic inflammatory markers. Sodium–glucose cotransporter-2 (SGLT2) inhibitors may alter oral microbiota composition and cause mucosal changes, while glucagon-like peptide-1 (GLP-1) receptor agonists may increase caries risk through gastrointestinal side effects and xerostomia; both drug classes warrant proactive dental monitoring. Conclusions: The bidirectional relationship between MetS and oral health supports integrated screening and interdisciplinary management. Routine periodontal assessment should be integrated into the metabolic risk management pathway, and dental professionals should screen patients with severe periodontitis for metabolic risk factors. The oral microbiome emerges as a promising target for future mechanistic research and therapeutic intervention. Recognition of oral health as an integral component of metabolic health may improve risk stratification, prevention, and long-term patient outcomes. Large-scale randomized controlled trials with standardized endpoints are needed to establish causal directionality and optimize combined therapeutic strategies. Full article

Background/Objectives: Cholesterol homeostasis is often framed as a dietary problem, but circulating low-density lipoprotein (LDL) biology is governed largely by endogenous sterol handling, with the liver acting as the principal integrative organ for cholesterol synthesis, LDL receptor-mediated clearance, very-low-density lipoprotein (VLDL) export, bile acid production, and biliary sterol disposal. This narrative review evaluates the hepatic basis of cholesterol regulation, statin pharmacology, gut microbial sterol metabolism, chronic hepatic inflammation, and a proposed oral–gut–liver–artery axis in atherogenesis. The aim of this narrative review is to clarify which elements of the proposed axis are established, which are supported but incomplete, and which remain hypothesis-generating. Methods: Mechanistic, translational, clinical, and review literature were synthesized to separate established mechanisms from emerging and speculative links. PubMed/MEDLINE, Scopus, and Google Scholar were searched from January 2000 through May 2026. Primary search terms included: cholesterol homeostasis, LDL receptor, SREBP2, statin pleiotropic effects, statin-associated muscle symptoms, gut microbiota cholesterol, bile salt hydrolase, MASLD, Porphyromonas gingivalis liver, phosphorylated dihydroceramides, serine dipeptide lipids Bacteroidetes, ceramide atherosclerosis, and oral–gut–liver–artery axis. Results: LDL/apoB causality and hepatic statin mechanism are well-established. Gut microbiota can alter cholesterol absorption, coprostanol formation, bile acid pools, and portal signaling, but these effects are context-dependent. Hepatic free cholesterol loading and lysosomal sterol stress are strongly implicated in the biology of metabolic dysfunction-associated steatotic liver disease (MASLD). Periodontal pathogens, especially Porphyromonas gingivalis, may contribute to liver and vascular inflammation through bacteremia, oral–gut translocation, innate immune activation, and bioactive bacterial sphingolipids. Phosphorylated dihydroceramides (PDHCs) and Bacteroidetes-derived serine dipeptide lipids have been detected in human arterial specimens and shown to enter host ceramide pools, providing a direct lipid metabolic pathway linking microbial community composition to vascular disease. Viridans streptococci and the Streptococcus anginosus group are inflammatory cofactors rather than proven causes of hepatic cholesterol overproduction. Conclusions: The strongest model involves microbial amplification of hepatic cholesterol dysmetabolism, endothelial activation, foam-cell formation, and plaque vulnerability acting on a host-derived LDL/apoB scaffold. This model is testable and should complement guideline-based LDL-lowering therapy. Full article

Background/Objectives: Activated irrigation techniques improve intracanal disinfection, but their impact on the clinical and radiographic healing of apical periodontitis remains unclear. This systematic review and meta-analysis evaluated the efficacy of passive ultrasonic irrigation (PUI) and laser-assisted irrigation (LAI), without adjunctive systemic antibiotics, on periapical healing compared with conventional irrigation in adult patients. Methods: Following PRISMA guidelines and prospective registration in PROSPERO (CRD420261413401), PubMed, Scopus, Embase, and Web of Science were searched up to February 2026. Randomized controlled trials (RCTs) involving adults with apical periodontitis comparing PUI or LAI against conventional syringe irrigation—with a minimum of 6 months follow-up—were included. Risk of bias was assessed using RoB 2, evidence certainty via GRADE, and a random-effects meta-analysis calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs). Results: Of 1115 records identified, five randomized controlled trials involving 451 teeth fulfilled the eligibility criteria and were included in the qualitative synthesis and quantitative meta-analysis. Activated irrigation significantly increased periapical healing probability compared with conventional irrigation (OR = 2.25; 95% CI: 1.29–3.93; p = 0.004), with no statistical heterogeneity (I² = 0%). Subgroup analyses showed significant benefits for both PUI (OR = 1.95; 95% CI: 1.08–3.54) and LAI (OR = 6.77; 95% CI: 1.63–28.12). The overall certainty of evidence was moderate due to risk of bias concerns. Conclusions: Activated irrigation techniques (PUI and LAI) were significantly associated with improved clinical and radiographic healing of apical periodontitis compared with conventional irrigation alone. Enhanced intracanal disinfection contributes to a more predictable resolution of periapical lesions without adjunctive systemic antibiotics. Further high-quality RCTs with standardized protocols and long-term CBCT-based follow-up are required to confirm these findings. Full article

Incretin-based therapies have transformed the management of obesity and type 2 diabetes mellitus (T2DM). Established agents—the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) semaglutide and liraglutide, and the dual GIP/GLP-1 receptor agonist tirzepatide—are now widely used, while a diverse pipeline of multi-receptor agents is advancing through late-phase development. GLP-1 receptors are expressed in several oral and other craniofacial tissues, raising the question of how these drugs affect oral health. This narrative review (PubMed, EMBASE, Scopus, Web of Science, Cochrane Library, ClinicalTrials.gov; January 2010–June 2026) integrates mechanistic studies, randomised controlled trials, pharmacovigilance data, society guidance, and the patient-facing phenomena increasingly raised in the dental chair. Preclinical and limited clinical evidence suggests that GLP-1 RAs may attenuate periodontal inflammation, while their effects on alveolar bone remain uncertain, reflecting both direct receptor and indirect metabolic influences. Concurrently, gastrointestinal adverse effects (nausea, vomiting, belching), reduced fluid intake, and possible salivary changes underlie a cluster of patient-reported complaints colloquially termed “Ozempic mouth”, “Ozempic teeth”, and “Ozempic breath”, alongside the facial soft-tissue changes seen in “Ozempic face”. Human oral-health-endpoint data remain scarce; much evidence is preclinical, indirect, or derived from case-level or pharmacovigilance reports. The oral cavity is nonetheless a plausible direct target of incretin pharmacotherapy and a practical monitoring site for tolerability. Dental practitioners should proactively manage the oral consequences of these agents, and validated oral health endpoints should be incorporated into future incretin trials. Full article

Background/Objectives: Resveratrol, a natural polyphenol with anti-inflammatory and antioxidant properties, has emerged as a promising adjunctive agent in periodontal therapy. This systematic review and meta-analysis evaluated evidence from in vitro, in vivo, and human clinical studies regarding the effects of resveratrol on periodontal disease, with the clinical component focusing on systemically healthy non-smoking patients. Methods: Electronic searches of MEDLINE/PubMed, Scopus, Embase, and Web of Science were conducted for studies published between 2000 and 2025. Eligible studies included periodontal-related in vitro cell models, in vivo experimental periodontitis models, and randomized clinical trials assessing resveratrol as an adjunctive therapy. Data extraction, risk-of-bias assessment, and meta-analyses were conducted in accordance with PRISMA guidelines. Results: Fifteen studies were included (five in vitro, six in vivo, and five human randomized controlled trials). Meta-analysis showed the inhibitory effect of resveratrol on the lipopolysaccharide-induced protein expression of IL-1β, IL-6, TNF-α, and IL-8 in vitro, with low to moderate heterogeneity. In animal studies, resveratrol significantly attenuated ligature-induced dental alveolar bone loss, IL-1β protein, and relative mRNA expression. However, reductions in relative mRNA expressions of TNF-α and IL-6 were inconsistent and highly heterogeneous; in contrast, nanoparticle- and liposomal-modified resveratrol consistently and significantly reduced these mRNA levels. In human trials, adjunctive resveratrol was associated with improvements in probing pocket depth and clinical attachment level compared with root planing alone in patients with periodontitis, as well as reductions in bleeding and plaque indices in patients with periodontal diseases, including gingivitis and periodontitis. Conclusions: Resveratrol suppresses pro-inflammatory cytokine expression in vitro and attenuates alveolar bone loss in vivo, with enhanced and more consistent molecular effects observed using modified formulations. Preliminary clinical evidence suggests that resveratrol may be associated with modest adjunctive effects on periodontal outcomes in systemically healthy non-smokers. However, given the limited number of clinical trials, small sample sizes, heterogeneity among studies, short follow-up periods, and limited certainty of the evidence, these findings should be interpreted cautiously. Further well-designed RCTs with longer follow-up periods are required to determine their clinical relevance. Full article

This narrative review synthesizes evidence linking periodontal dysbiosis with Alzheimer’s disease, all-cause dementia, and dementia-relevant mechanisms, focusing on the red complex pathogens P. gingivalis, T. denticola, and T. forsythia and on the translational meaning of periodontal therapy. A PubMed-centered literature search up to May 2026 informed this synthesis (a narrative review, not a registered systematic review or meta-analysis) of 46 periodontal-scope sources, supplemented by five contextual references identified outside the periodontal search (51 references in total). P. gingivalis shows the strongest mechanistic support, including gingipains, lipopolysaccharide, outer membrane vesicles, endothelial stress, and neuroinflammatory signaling; T. denticola shows moderate biological plausibility; and T. forsythia remains mainly hypothesis-generating. Human studies associate periodontitis, tooth loss, oral-hygiene indicators, and periodontal-care exposure with dementia-relevant outcomes, but residual confounding, reverse causation, dental-care access, and heterogeneous endpoints preclude causal inference. Notably, direct targeting of a single periodontal pathogen has not shown clinical benefit, as the gingipain inhibitor atuzaginstat failed in the GAIN trial, contrasting with the modest success of amyloid-targeting therapies. Current evidence supports graded plausibility rather than causal certainty, and a registered multi-database systematic review with neurological endpoints is needed before meta-analytic clinical claims can be made. Full article

Background: Type 2 diabetes mellitus (T2DM) and periodontitis are chronic inflammatory conditions. Periodontitis may amplify low-grade systemic inflammation in people with T2DM. High-sensitivity C-reactive protein (hsCRP) reflects this inflammatory burden, but the effect of non-surgical periodontal therapy (NSPT) on hsCRP in T2DM remains uncertain. Objective: To evaluate whether NSPT changes hsCRP at 3 and 6 months compared with oral hygiene instructions alone in patients with T2DM and periodontitis. Methods: Predefined secondary analysis of a 1:1 parallel-group randomized trial with assessments at baseline, 3 months, and 6 months. Participants received scaling and root planing plus oral hygiene instructions (intervention) or oral hygiene instructions only (control). Fasting hsCRP (mg/L) was analyzed on the log scale using mixed-effects models; effects are presented as exponentiated ratios with 95% confidence intervals. Sensitivity analyses included baseline-adjusted analysis of covariance (ANCOVA) and covariate-adjusted mixed models. An exploratory group-adjusted regression examined associations between periodontal changes and hsCRP change. Results: Eighty-nine participants were randomized (45 control, 44 intervention), with hsCRP available for most participants through 6 months. There was no between-group difference at 3 months (ratio 0.958; 95% CI 0.875–1.049; p = 0.358). At 6 months, hsCRP was lower in the NSPT group than in controls (ratio 0.809; 95% CI 0.738–0.887; p < 0.001), corresponding to ~19% lower hsCRP; the model-based geometric mean hsCRP at 6 months was 2.66 mg/L versus 3.26 mg/L. Periodontal measures improved more with NSPT, but changes in periodontal measures were not independently associated with hsCRP change after group adjustment. Conclusions: In patients with T2DM and periodontitis, NSPT was associated with lower hsCRP at 6 months compared with oral hygiene instructions alone. These biomarker findings suggest a potential systemic anti-inflammatory effect, but should be interpreted as hypothesis-generating and confirmed in adequately powered trials. Full article

Background: Crown lengthening procedures are widely used in restorative and periodontal therapy to expose sufficient tooth structure for functional and esthetic rehabilitation. Traditionally performed using an open-flap approach, these procedures have evolved with the introduction of minimally invasive flapless techniques. This narrative review aims to summarize the biological foundations, clinical outcomes, and contemporary approaches associated with crown lengthening procedures, with particular emphasis on flapless and flap techniques, healing processes, technological advancements, and clinical decision-making considerations. Methods: A narrative literature review was conducted using electronic databases, including PubMed, Scopus, and Web of Science, to identify relevant publications on crown lengthening procedures. The search focused on studies addressing flapless and flap techniques, biological principles, healing dynamics, clinical outcomes, postoperative considerations, and contemporary approaches such as laser-assisted and digitally guided procedures. Titles and abstracts were screened for relevance, followed by full-text assessment of eligible articles. The study selection process was documented using a simplified PRISMA-style flow diagram to enhance transparency. Results: The reviewed literature suggests that flapless crown lengthening may be associated with reduced surgical time, less postoperative discomfort, faster healing, and preservation of soft tissue architecture in appropriately selected cases. However, its applicability appears to be influenced by anatomical factors, including bone morphology and the need for adequate visualization during osseous recontouring. Conventional flap techniques continue to be widely used and may offer improved surgical access and visibility, particularly in more complex situations requiring extensive bone modification. Although these procedures have been associated with longer healing periods and greater postoperative morbidity, the heterogeneity of the available evidence and the narrative nature of this review limit definitive comparisons between the two approaches. Conclusions: In conclusion, both flapless and flap crown lengthening procedures demonstrate high clinical efficacy when appropriately indicated. The choice of technique should be guided by case-specific factors, clinician expertise, and patient expectations. Further randomized controlled trials are recommended to strengthen the evidence base and establish standardized clinical guidelines. Full article

Background: Artemisia absinthium (A. absinthium) is a perennial plant valued for its antibacterial, antioxidant, and anti-inflammatory properties, exhibiting broader therapeutic potential. Given the need to deliver low doses of A. absinthium extract, mesoporous silica nanoparticles have attracted considerable attention as promising nanocarriers due to their distinctive physical and chemical properties. Methods: Physicochemical characterization of the materials was performed and biological assays were conducted to investigate the ROS, antibacterial and antioxidant activity of A. absinthium extract encapsulated within cerium- and calcium-doped mesoporous silica nanoparticles (MNSiCaCe) against both aerobic and anaerobic bacteria. Results: FTIR, SEM, and BET analysis confirmed successful synthesis of the MNSiCaCe. Phytochemical profiling of Artemisia absinthium extract using HPLC revealed the presence of artemisinin and a rich composition of phenolic and flavonoid constituents, with a total phenolic content of 182 ± 3.6 mg GAE/100 g dry plant material and a total flavonoid content of 42.5 ± 0.6 mg QE/100 g. Quantitative drug loading profiling demonstrated that while plain MNSi nanocarriers achieved a loading capacity of 16.96%, the MNSiCaCe enhanced this threshold to 43.11%. The in vitro controlled-release kinetics exhibited a highly prolonged and slow-release profile of the MNSiCaCe. The materials demonstrated excellent hemocompatibility and high mitochondrial activity with human periodontal ligament cells (hPDLCs). Elevated ROS generation was observed under conditions where antibacterial activity was most pronounced. While the artemisinin-doped nanoparticles showed notable antibacterial effects, the complete Artemisia absinthium-loaded nanoparticles achieved a significantly greater reduction in bacterial viability probably due to the synergistic interaction between artemisinin and the extract’s rich polyphenol profile. Conclusions: These findings highlight MNSiCaCe as a promising and safe nanocarrier system for drug delivery, with strong antibacterial potential, offering valuable applications in antibacterial therapies. Full article

Background: Tooth-supported fixed dental prostheses (FDPs) remain relevant when implant therapy is limited, but their mechanical behavior depends on material selection, connector design, retainer design, prosthesis configuration, and abutment support. This systematic review assessed how these factors affect fracture behavior and stress transmission in tooth-supported FDPs. Materials and Methods: PubMed/MEDLINE, Scopus, Web of Science Core Collection, and Dentistry and Oral Sciences Source were searched for English-language studies published from 1 January 2016 to 15 May 2026. Eligible studies were in vitro mechanical, fatigue, fracture-resistance, or finite element analysis (FEA) studies of tooth-supported FDP designs. Clinical studies were screened during eligibility assessment, but no clinical study met the final inclusion criteria for primary synthesis. In vitro components were appraised with the Quality Assessment Tool for In Vitro Studies (QUIN), and FEA components were appraised with the Risk-of-bias Framework for Dental Finite Element Analysis (ROBFEAD). Findings were synthesized narratively by evidence type and biomechanical theme. Results: Twenty-nine studies were included: 11 in vitro-only studies, 14 FEA-only studies, and four combined experimental and computational studies. No eligible clinical study met the final inclusion criteria. Zirconia-based systems were the most frequent focus. Their behavior depended on connector dimensions, connector shape, framework design, span, retainer configuration, loading direction, abutment selection, periodontal support, and bone support. Larger connector dimensions or greater connector height often improved fracture resistance or reduced modeled stress in zirconia models, but connector area alone did not explain performance across all materials and designs. Conservative FDPs were sensitive to retainer geometry, adhesive-interface behavior, connector design, and abutment support. Conclusions: Current evidence is limited to laboratory and computational studies. Tooth-supported FDP biomechanics should be interpreted as a material, design, and support system, not as a material effect alone. Full article

Background/Objectives: Contemporary periodontal therapy is increasingly guided by evidence-based clinical protocols, particularly the European Federation of Periodontology (EFP) S3 Clinical Practice Guidelines. The present study aimed to assess dentists’ perceptions regarding modern periodontal therapy and to perform a preliminary psychometric evaluation of a newly developed questionnaire. Methods: A cross-sectional questionnaire-based study was conducted among 109 dental practitioners. The questionnaire evaluated perceptions regarding non-surgical periodontal therapy, surgical periodontal therapy, and the comparative role of both therapeutic approaches. Descriptive statistical analysis, internal consistency analysis using Cronbach’s Alpha, Intraclass Correlation Coefficient (ICC), repeated measures ANOVA, and exploratory factor analysis (Principal Component Analysis—PCA) with Varimax rotation were performed to evaluate the psychometric properties of the instrument. Results: The questionnaire demonstrated good internal consistency, with Cronbach’s Alpha values ranging from 0.77 to 0.86. ICC analysis confirmed satisfactory reliability. Respondents showed favorable attitudes toward evidence-based periodontal management, supporting non-surgical therapy as first-line treatment and the staged integration of surgical approaches in complex cases. Exploratory factor analysis identified a coherent factorial structure, with four components explaining 73.94% of the total variance. Conclusions: The questionnaire showed good psychometric properties, supporting its potential utility as a reliable and useful instrument for evaluating professional attitudes and clinical decision-making in periodontology. Full article

Background/Objectives: The interplay between oral and systemic diseases is highlighted by the shared inflammatory mechanisms and epidemiological associations between periodontitis and rheumatoid arthritis (RA). Building on previous syntheses of the effect of periodontal therapy on RA disease activity, we sought to refine the evidence base through strict restriction to randomized controlled trials (RCTs), separate analysis of the two non-interchangeable formulations of the Disease Activity Score on 28 joints (DAS28-CRP and DAS28-ESR, based on either C-reactive protein or erythrocyte sedimentation rate, respectively), and inclusion of recent randomized trials. We aimed to determine whether the first two steps of periodontal therapy (steps 1 and 2 of the 2020 EFP S3-level clinical practice guideline), delivered through supragingival professional mechanical plaque removal and subgingival instrumentation, reduce DAS28 in adults with concurrent RA and periodontitis. Methods: The review protocol was registered in PROSPERO (CRD420261400735). Five databases were searched in accordance with PRISMA 2020. Only RCTs were eligible. Risk of bias was assessed with RoB-2. DAS28-CRP and DAS28-ESR were analyzed in separate random-effects forest plots. Sensitivity analyses addressed adjunctive antibiotics and high baseline disease activity. Results: Ten trials (n = 430 randomized patients) were included. At 3 months, DAS28-CRP was significantly reduced (between-group MD = −0.84, 95% CI −1.38 to −0.29; change-from-baseline MD = −0.55, −0.92 to −0.19). On DAS28-ESR at 3 months, the change-from-baseline estimate was significant (MD = −1.27, −2.22 to −0.31) and the follow-up estimate concordant in direction but not significant (MD = −0.89, −1.85 to 0.07), with substantial heterogeneity. Conclusions: Periodontal therapy may be associated with short-term reductions in RA disease activity, particularly DAS28-CRP at 3 months, with directionally concordant but less certain effects on DAS28-ESR. The evidence remains limited by small sample sizes, risk of bias, substantial heterogeneity of the DAS28-ESR estimates, and sparse follow-up beyond 3 months. As no trial reported individual responder categories, these group-level findings support periodontal therapy as a possible adjunctive measure in RA rather than a predictable, clinically meaningful benefit at the individual patient level. Full article

Background/Objectives: Chronic kidney disease (CKD) is associated with numerous oral manifestations that may negatively affect quality of life, nutrition, and overall health. This narrative review aimed to summarize current evidence regarding oral manifestations of CKD and kidney transplantation, examine their proposed underlying mechanisms, and discuss implications for dental management. Methods: A structured literature search of PubMed/MEDLINE was conducted for English-language publications from January 2000 to March 2026. Original studies, systematic reviews, meta-analyses, clinical guidelines, and relevant narrative reviews were included. Additional references were identified through manual screening of bibliographies. Results: Oral manifestations associated with CKD include xerostomia, periodontal disease, oral infections, anemia-related mucosal pallor, developmental enamel defects, and medication-related gingival overgrowth. Kidney transplant recipients are additionally at risk of opportunistic infections and oral malignancies related to long-term immunosuppressive therapy. While oral diseases, particularly periodontal disease and oral infections, may contribute to systemic inflammation, much of the available evidence remains observational. Similarly, many recommendations for dental management are based on expert consensus and clinical experience rather than high-quality interventional studies. Conclusions: Oral complications are common throughout the CKD continuum and warrant regular assessment and preventive care. Multidisciplinary collaboration is essential, while further prospective studies are needed to strengthen the evidence base for clinical management. Full article

Background/Objectives: This study aimed to evaluate the gingival crevicular fluid (GCF) levels of fractalkine/CX3CL1 and CX3CR1 in patients with gingivitis and periodontitis before and after non-surgical periodontal therapy. Methods: A total of 90 individuals comprising 30 with stage 3 periodontitis, 30 with gingivitis, and 30 periodontally healthy, were enrolled in the study. Gingivitis and periodontitis patients underwent non-surgical periodontal treatment. GCF samples were collected at baseline and at 1 and 3 months after treatment. CX3CL1 and CX3CR1 were measured by an ELISA analysis. Results: GCF CX3CL1 and CX3CR1 were significantly elevated in patients with periodontitis and gingivitis compared to healthy controls (p < 0.001). The periodontitis patients also showed higher GCF levels of CX3CL1 and CX3CR1 than those with gingivitis (p < 0.001). Significant decreases in GCF CX3CL1 and CX3CR1 were detected at 1 month after periodontal treatment compared to baseline values in both the gingivitis and periodontitis patients (p < 0.001). Moreover, the periodontitis patients exhibited significant decreases in both CX3CL1 and CX3CR1 levels at 3 months post-treatment compared to 1 month (p < 0.001), whereas no significant changes were observed between the two time points in the gingivitis patients (p > 0.05). Conclusions: Our findings suggest that the CX3CL1–CX3CR1 axis might contribute to the inflammatory processes of periodontal diseases and may represent a treatment-responsive component of the local host response. Full article

Background/Objectives: This prospective observational cohort study aimed to evaluate the influence of heated tobacco (HT) and electronic cigarettes (ECs) on bone remodeling markers such as receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG), and periodontal status, at baseline and at 3 months after initial periodontal therapy. Methods: The sample comprised 236 participants (130 women, 106 men; mean age 38.96 ± 7.69 years), distributed across non-smokers (n = 72), heated tobacco/HT product users (n = 83), and electronic cigarette/EC users (n = 81). For each patient, the periodontal charting included periodontal probing depth (PPD), bleeding on probing (BOP), and clinical attachment loss (CAL). Unstimulated saliva samples were analyzed for RANKL and OPG levels. All patients underwent nonsurgical periodontal therapy (scaling and root planing). Between-group comparisons were performed using the Kruskal–Wallis test followed by Bonferroni-adjusted pairwise comparisons, while within-group changes over time were assessed using the Wilcoxon signed-rank test. To complement the primary nonparametric analyses, two-way mixed-design ANOVA and ANCOVA models adjusted for baseline values and periodontitis stage were performed as sensitivity analyses. Statistical significance was set at p < 0.05. Results: At baseline, both product user groups exhibited significantly higher PPD (p = 0.005) and CAL (p = 0.001) compared with non-smokers, with no differences between HT and EC users. Salivary RANKL levels were significantly higher in HT and EC users than in non-smokers, and OPG levels did not differ significantly. Following non-surgical periodontal therapy, all parameters improved significantly across groups (p < 0.001). At the 3-month follow-up, both product user groups maintained higher PPD (p = 0.008), CAL (p = 0.001), and salivary RANKL levels, compared with non-smoking individuals (p < 0.001). The RANKL/OPG ratio remained significantly different only for EC users compared with non-smokers (p < 0.001). Conclusions: HT and EC use were associated with differences in periodontal parameters and higher RANKL levels, while differences in the RANKL/OPG ratio were observed in EC users compared with non-smokers. Non-surgical periodontal therapy improved clinical parameters and reduced the RANKL/OPG ratio, highlighting the importance of biofilm control. Full article