Search Results (62)

Periodontal disease represents a major global health burden, beginning with gingivitis and progressing to periodontitis, which causes connective tissue breakdown, alveolar bone resorption, and eventual tooth loss. Beyond local pathology, periodontitis is a chronic inflammatory condition with systemic associations, including cardiovascular disease, diabetes, and metabolic disorders. Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) have emerged as promising candidates for periodontal regeneration. This review aimed to map the current evidence on MSC-derived EVs (MSC-EVs) in periodontal regeneration, focusing on their mechanisms of action, therapeutic potential, and translational challenges. A comprehensive literature search was conducted across a major biomedical database (PubMed) to identify preclinical and clinical studies investigating MSC-EVs in the context of periodontitis. Data were charted on EV cargo composition, biological functions, regenerative outcomes, and reported limitations. Evidence indicates that MSC-EVs encapsulate bioactive molecules—including antimicrobial peptides, proteins, lipids, and microRNAs—that modulate immune responses, suppress pro-inflammatory signaling, and promote angiogenesis and tissue repair. In periodontal models, MSC-EVs attenuate osteoclast activity, enhance fibroblast proliferation, and stimulate extracellular matrix remodeling, supporting regeneration of periodontal ligament and alveolar bone. Exosome-based approaches demonstrate advantages such as reduced immunogenicity, improved safety, and feasibility for storage and standardization. However, most findings remain preclinical, with limited human data available. To bridge the translational gap, well-designed clinical trials are needed to confirm efficacy and safety while addressing regulatory challenges, GMP standards, and outcome measures. Harnessing their regenerative capacity while mitigating side effects may guide precision-targeted therapies, and continued mechanistic studies with standardized production will be key to advancing MSC-EVs into clinical practice. Full article

Periodontitis is a chronic inflammatory disease driven by microbial dysbiosis and an exacerbated host immune response. This leads to progressive breakdown of periodontal tissues. Although scaling and root planing remains the standard treatment, its capacity to fully restore immune balance and host–microbiota homeostasis is limited. Probiotics have emerged as promising adjunctive strategies to modulate pathways involved in periodontal disease progression. This review aimed to evaluate current clinical evidence on the use of probiotics as adjuncts in periodontal therapy. The review followed the Scale for the Assessment of Narrative Review Articles criteria, applied exclusively as a reporting-quality framework. A literature search was conducted in MEDLINE via PubMed for manuscripts indexed through January/2026, using MeSH terms related to periodontitis and probiotics. Probiotics demonstrate potential as adjunctive agents in periodontal therapy, as evidenced by improvements in clinical parameters (probing depth, clinical attachment level, and/or bleeding on probing) reported in clinical studies. However, the findings remain heterogeneous across trials. Variability in probiotic strains, CFU concentrations, administration routes, and treatment durations highlights the need for standardized clinical protocols to improve comparability and reproducibility and better establish their clinical efficacy. Stronger, long-term evidence is required to standardize therapeutic protocols. Full article

Background/Objectives: Periodontitis and diabetes mellitus (DM) are chronic inflammatory conditions that share common biological mechanisms, including systemic inflammation and insulin resistance. Adipokines are considered key mediators in this interrelationship; however, the roles of many adipokines remain unclear. Apelin and asprosin are relatively novel adipokines that have not yet been sufficiently investigated in dentistry. Therefore, this study aimed to evaluate salivary apelin and asprosin levels in periodontally healthy individuals, patients with periodontitis, and patients with periodontitis + DM and to investigate their associations with clinical periodontal parameters. Methods: A total of 90 individuals were included in the study, comprising 30 periodontally healthy subjects, 30 with periodontitis, and 30 with periodontitis and DM. Clinical periodontal indices and body mass index (BMI) were measured for each participant. Unstimulated saliva was collected from each participant, and apelin and asprosin concentrations were analyzed using an enzyme-linked immunosorbent assay (ELISA). The normality of continuous variables was examined with the Shapiro–Wilk test. For non-normally distributed data, non-parametric procedures such as the Mann–Whitney U and Kruskal–Wallis tests were applied. Comparisons of categorical variables between groups were performed using Pearson’s chi-square or the Fisher–Freeman–Halton test. Associations between continuous parameters were assessed through Spearman’s rank correlation analysis. A significance threshold of 5% (p < 0.05) was adopted for all statistical evaluations. Results: No significant intergroup differences were detected for age, gender, or BMI. The healthy group exhibited significantly lower plaque index (PI), gingival index (GI), and probing depth (PD) scores compared with both periodontitis groups, and these differences reached statistical significance (p < 0.001).The median salivary apelin level in the periodontitis + DM group was significantly reduced relative to the healthy group (p = 0.009). However, salivary asprosin concentrations did not differ significantly among the groups (p = 0.053). Spearman’s correlation analysis revealed positive correlations between asprosin and PD and clinical attachment loss (CAL), whereas apelin showed negative correlations with these parameters. Conclusions: Salivary apelin may serve as a potential biomarker for distinguishing healthy individuals from those with diabetic periodontitis. The opposing correlation patterns indicate that apelin and asprosin may be differentially related to periodontal tissue breakdown. However, further longitudinal and mechanistic studies are required to clarify the biological significance of these associations. Full article

Background: Hypoxic and oxidative stress states tightly regulate bone and periodontal remodeling, yet the field lacks an integrated conceptual framework explaining how fluctuating oxygen availability and redox signaling determine anabolic versus catabolic outcomes. Although hypoxia-inducible factor-1α (HIF-1α), reactive oxygen species (ROS), and reperfusion injury are individually well-studied, their coordinated role in defining tissue remodeling thresholds remains unclear. Methods: This Perspective synthesizes mechanistic evidence from cellular, molecular, and tissue-level studies on hypoxia, redox biology, perfusion dynamics, osteoimmunology, and bone remodeling. Published data were evaluated to characterize how oxygen tension, ROS generation, and inflammatory signaling interact under mechanical or metabolic stress. A conceptual model (“Hypoxostat Model”) was constructed to describe the regulatory balance between hypoxia-driven catabolism and oxygenation-driven anabolism. Hypothesis: The Hypoxostat Model proposes that tissues operate within a dynamic oxygen-dependent regulatory window. Moderate hypoxia transiently activates HIF-1α, angiogenesis, and osteogenic compensation, whereas deeper or sustained hypoxia collapses perfusion, increases ROS, amplifies IL-1β/TNF-α/IL-17A signaling, and promotes RANKL-mediated osteoclastogenesis. Reoxygenation phases trigger additional oxidative bursts, further biasing tissues toward destructive remodeling. Thin periodontal phenotypes exhibit reduced perfusion reserve and increased sensitivity to hypoxia–ROS transitions, lowering their threshold for entry into catabolic remodeling domains. Conclusions: Hypoxia and redox signaling function as a bistable regulatory system controlling bone and periodontal remodeling. The Hypoxostat Model provides a unifying framework linking oxygen tension, ROS dynamics, inflammatory cytokines, and remodeling outcomes. Recognizing hypoxia–reoxygenation behavior as a mechanistic switch may improve prediction of tissue vulnerability and guide therapeutic strategies aimed at modulating redox balance or enhancing local perfusion. Full article

Background: This retrospective study assessed long-term survival outcomes of severely periodontally compromised mandibular incisors (≥50% bone loss) following initial periodontal treatment and a structured recall protocol. Methods: Ninety-three patients with ≥50% bone loss in all mandibular incisors were treated in a private practice over a 32-year period by the same periodontist. Following initial treatment, patients were assigned 6- or 12-month recall intervals based on response and motivation. The baseline was set after subgingival debridement (visit 3). Last follow-up visit (LFV) in this study was defined as follows: the last control visit of the patients done by the periodontist. ‘Survival’ was divided into 3 groups: complete survival (CS), all incisors were still present, and partial survival (PS), one or two incisor(s) were lost. Total failure (TF) involved instances in which all incisors were lost. Effective survival was monitored when an extracted tooth was repositioned and stabilized with a splint, ensuring preservation of function. Only 9.7% of patients needed a mandibular incisal splint. For reasons of consistency the CPITN was used. Statistical analysis was performed in R. The significance level was set at α = 0.05. Event-free patients can be considered as uninformative censoring, all with the same probability of risk, as they all were still in follow-up at the time of informed consent approval. Results: A total of 93 patients were included in the study. The mean follow-up was 17.7 years. At the last visit, 79.6% of patients retained all incisors, with an effective survival rate of 89.2%. Regarding the survival probability over time, after 15 years, it is 91% (95% CI: 0.86–0.98), and after 20 years, it is 78% (95% CI: 0.69–0.90). The effective survival probability over time after 15 years was 95% (95% CI: 0.91–1.0), and after 20 years, it was 89% (95% CI: 0.81–0.98). Compliance significantly influenced survival (p = 0.007), whereas the number of occluding units did not (p = 0.226). The total amount of teeth lost during the entire follow-up period showed a statistically significant difference compared to survival (p < 0.001). The general periodontal health of the patient population presented a shift from CPITN 3 to the 0–2 group. Conclusions: Severely compromised mandibular incisors demonstrate high long-term survival rates with appropriate therapy. After 20 years the survival probability was 78%, and the effective survival probability, 89%, underscoring the critical role of lifelong periodontal care. Mandibular incisor preservation over long-term follow-up is highly achievable. Full article

Cellular senescence is a fundamental biological process characterized by stable cell cycle arrest, resistance to apoptosis, and the acquisition of a pro-inflammatory senescence-associated secretory phenotype (SASP). While senescence plays essential roles in development, tissue homeostasis, and tumor suppression, its accumulation with age and chronic stress contributes to tissue dysfunction and disease. In the oral cavity, where tissues are continuously exposed to mechanical stress, microbial challenge, and environmental insults, senescence has emerged as a critical regulator of both health and pathology. This review provides an overview of the defining hallmarks of cellular senescence, the molecular mechanisms driving its onset, and its physiological and pathological consequences, with a particular focus on oral tissues. We highlight the beneficial roles of senescence in maintaining oral tissue integrity, facilitating wound repair, suppressing malignant transformation, and promoting immune-mediated clearance of damaged cells. Conversely, we discuss the detrimental effects of persistent senescent cell accumulation, including oral aging phenotypes, chronic inflammation, alveolar bone loss, periodontal breakdown, salivary gland dysfunction, and contributions to oral carcinogenesis. Finally, we examine emerging therapeutic strategies targeting senescence in oral disease management, including senolytic and senomorphic approaches, immune-based clearance mechanisms, and gene- and cell-based interventions aimed at delaying or modulating senescence. Understanding the dualistic nature of cellular senescence in the oral environment may inform novel preventive and therapeutic strategies to promote oral health and mitigate age- and disease-associated oral pathologies. Full article

Background: Schizophrenia is strongly associated with severe oral health deterioration, driven by cognitive deficits, behavioral dysfunction, and medication-related biological changes. Objective: To examine how neurocognitive dysfunction in schizophrenia, particularly cognitive deficits, is associated with poorer oral hygiene control, motivation, and self-regulation, contributes to oral health decline by disrupting everyday oral hygiene behaviors and dental care engagement, and to discuss the implications of this framework for interdisciplinary prevention strategies. Methods: This manuscript follows a narrative review design aimed at conceptually integrating evidence on neurocognitive mechanisms underlying oral health decline in schizophrenia. To identify relevant literature, a targeted search of PubMed/MEDLINE, Scopus, and Web of Science was conducted, covering publications from 2000 to 2025. The search strategy was used to support thematic exploration and conceptual synthesis, rather than to perform a systematic study selection or quantitative evidence aggregation. This narrative review summarizes findings from 90 peer-reviewed studies selected from the available literature. Results: Executive dysfunction, attentional deficits, and low motivation impair routine oral hygiene and delay dental care-seeking. Antipsychotic-induced xerostomia, metabolic disturbances, oxidative stress, immune dysregulation, and oral microbiome dysbiosis accelerate periodontal breakdown and caries progression. These interacting processes generate a self-reinforcing cycle of inflammation, tissue destruction, and treatment avoidance. Epidemiological data show markedly elevated DMFT/DMFS indices and up to a three-fold higher risk of edentulism compared with the general population. Emerging evidence suggests that integrated psychiatric–dental care models may be associated with improvements in oral health and care engagement, although current findings are largely preliminary and based on small or heterogeneous study populations, including related neurocognitive disorders. Conclusions: Unlike existing epidemiological syntheses, this review highlights oral health deterioration in schizophrenia as a functionally mediated consequence of neurocognitive impairment, underscoring the need for preventive approaches aligned with patients’ cognitive and motivational capacities. Full article

Background: Adult patients with a thin buccal cortical plate and fragile periodontal phenotype are at high risk of dehiscence, fenestration and recession during transverse orthodontic expansion. Conventional mechanics often create a cervical compression-dominant environment that exceeds the adaptive capacity of the periodontal ligament (PDL)–bone complex. Objectives: This study proposes an integrative mechanobiological model in which a skeletal-anchorage-assisted loading protocol (Bone Protection System, BPS) transforms expansion into a tension-dominant regime that favours buccal phenotype preservation. Methods: Patient-specific finite element models were used to compare conventional expansion with a BPS-modified force system. Regional PDL stress patterns and crown/apex displacement vectors were analysed to distinguish tipping-dominant from translation-dominated mechanics. A pilot CBCT proof-of-concept (n = 1 thin-phenotype adult) with voxel-based registration quantified changes in maxillary and mandibular alveolar ridge width and buccal cortical plate thickness before and after BPS-assisted expansion. The mechanical findings were integrated with current evidence on compression- versus tension-driven inflammatory and osteogenic pathways in the PDL and cortical bone. Results: FEM demonstrated that conventional expansion concentrates high cervical compressive stress along the buccal PDL and cortical surface, accompanied by bending-like crown–root divergence. In contrast, the BPS protocol redirected forces to create a buccal tensile-favourable region and a more parallel crown–apex displacement pattern, indicative of translation-dominated movement. In the proof-of-concept (n = 1) CBCT case, BPS-assisted expansion was associated with preservation or increase of buccal ridge dimensions without radiographic signs of cortical breakdown. Conclusions: A tension-dominant orthodontic loading environment generated by a skeletal-anchorage-assisted force system may support buccal cortical preservation and vestibular phenotype reinforcement in thin-phenotype patients. The proposed mechanobiological model links these imaging and FEM findings to known molecular pathways of inflammation, angiogenesis and osteogenesis. It suggests a functional biomaterial-based strategy for widening the biological envelope of safe tooth movement. Full article

The peptidylarginine deiminase (PAD) family includes five isozymes (PAD1–4 and PAD6) with unique tissue distributions and substrate specificities. These enzymes facilitate citrullination, a post-translational modification where positively charged arginine residues are converted into neutral citrulline residues in the presence of calcium ions. This process significantly changes protein properties, affecting molecular interactions, structural stability, and biological functions. Over the past six years (2019–2025), there has been significant progress in understanding PAD activity mechanisms and their therapeutic potential. Recent discoveries include the regulated nuclear translocation of PAD2, PAD4’s specific role in forming cancer extracellular chromatin networks (CECNs), and the development of next-generation inhibitors with greatly improved pharmacological profiles. PAD4 is crucial in forming neutrophil extracellular traps (NETs). Citrullination of histones H3 and H4 by PAD4 destabilizes chromatin, helping release DNA-protein networks as an antibacterial defense. However, excessive NET formation can contribute to autoimmune diseases and thrombosis. Similarly, the bacterial peptidylarginine deiminase from Porphyromonas gingivalis (PPAD)—the only known prokaryotic citrullinating enzyme—plays a key role. Working with R-gingipains, PPAD triggers pathological citrullination of host proteins, leading to immune tolerance breakdown and linking periodontal disease with systemic autoimmune disorders such as rheumatoid arthritis, atherosclerosis, and Alzheimer’s disease. Once thought to be a rare post-translational modification, citrullination is now understood as a vital regulatory mechanism in both normal physiology and disease, involving both internal processes of homeostasis and external mechanisms of bacterial pathogenesis. Full article

Background: Periodontitis is a multifactorial inflammatory disease influenced by immune and genetic factors. Certain genetic and immunological disorders, such as Down syndrome (DS), Leukocyte Adhesion Deficiency type I (LAD-I), and Papillon–Lefèvre syndrome (PLS), are associated with early-onset and severe periodontitis. Understanding their molecular and immunological mechanisms is crucial for advancing personalized therapeutic approaches. Methods: A systematic review was conducted following PRISMA 2020 guidelines to compare inflammatory gene expression profiles in patients with periodontitis associated with genetic or immune-mediated disorders and those without systemic conditions. Searches were performed in PubMed, Scopus, Web of Science, and Embase for studies published between 2010 and June 2025. Eligible studies reporting cytokine profiles or inflammatory gene expression were included and analyzed. Results: Six case–control studies met the inclusion criteria: three on DS, two on LAD-I, and one on PLS. DS patients showed increased serum levels of IL-1 beta, TNF-alpha, IL-4, IL-10, and IFN-gamma, with dysregulation of STAT1, STAT3, and SOCS3. LAD-I was characterized by overexpression of IL-17A, IL-6, IL-23, G-CSF, CXCL2, and CXCL5, indicating IL-17–driven inflammation and excessive neutrophil activation. In PLS, cathepsin C deficiency impaired activation of the antimicrobial peptide LL-37, leading to compromised host defense and accelerated tissue breakdown. Conclusions: Patients with periodontitis linked to genetic or immune-mediated disorders exhibit distinct inflammatory gene expression signatures that enhance disease susceptibility and progression. Identifying these immunoinflammatory pathways may guide precision periodontal therapies, although larger, standardized studies are required to validate these findings. Full article

Oral health represents a complex interplay between local microbial ecology, host immune responses, and systemic physiology. Far from being an isolated entity, the oral cavity is the entry point of the gastrointestinal and respiratory tracts and harbors up to one trillion microorganisms. While commensal species maintain ecological balance, pathogenic bacteria such as Porphyromonas gingivalis drive inflammatory conditions like gingivitis and periodontitis. Studies suggest that as chronic inflammation persists and is manifested through sustained breakdown of periodontal tissues, systemic dissemination of oral pathogens contributes to bacteremia, endothelial dysfunction, and neuroinflammation. As a result, increasing evidence has been found linking these oral pathogens and inflammatory mediators to systemic conditions including Alzheimer’s disease, cardiovascular disease, and arthritis. This narrative review synthesizes current evidence linking oral health to systemic disease while addressing practical strategies to strengthen preventive care. Evidence-based interventions are presented as accessible tools for reducing both oral and systemic inflammatory burden. Importantly, this article emphasizes the public health imperative of bridging mechanistic insights with actionable oral hygiene practices. By promoting evidence-based strategies such as scaling and root planing, dietary sugar reduction, and judicious use of antimicrobial agents, individuals may reduce their risk of chronic inflammatory and degenerative diseases. Future interdisciplinary research is needed to clarify causal mechanisms and optimize preventive frameworks integrating oral-systemic health. Full article

Background/Objectives: Periodontitis and diabetes mellitus are known to exert a bidirectional pathogenic influence characterized by metabolic dysregulation, exaggerated inflammatory response, and accelerated periodontal breakdown. Despite the increasing prevalence of both conditions in Eastern Europe, comparative clinical data from Romanian populations remain limited. This study aimed to assess differences in periodontal status, systemic comorbidities, smoking exposure, and local periodontal risk factors between diabetic and non-diabetic individuals in a Romanian cohort. Methods: This cross-sectional study included 345 adults (152 with diabetes; 193 non-diabetic individuals) all diagnosed with periodontitis. Although participants were recruited to achieve comparable distributions of sex and smoking status, individuals with diabetes were significantly older than controls. Full-mouth periodontal examination was performed following the 2018 EFP/AAP classification criteria. Clinical parameters included probing pocket depth (PPD), clinical attachment level (CAL), plaque index (PI), and bleeding on probing (BOP). Periodontal staging and grading were determined, and local risk factors were recorded using a multiple-response approach. Systemic comorbidities and smoking exposure were also evaluated. Statistical analyses involved t-tests, chi-squared tests, and Spearman correlations; significance was set at p < 0.05. Results: Diabetic patients exhibited significantly higher mean PPD (4.33 ± 1.22 mm vs. 3.70 ± 0.86 mm; mean difference 0.63 mm, 95% CI: 0.45–0.81), greater CAL (mean difference 0.19 mm, 95% CI: 0.01–0.37), and elevated PI and BOP (PI mean difference 18.97%, 95% CI: 12.44–25.50; BOP mean difference 17.23%, 95% CI: 10.86–23.60). Advanced stages (III–IV) and Grade C periodontitis were more prevalent among diabetic individuals. Diabetic participants also presented a higher burden of local plaque-retentive factors and systemic comorbidities (notably hypertension and cardiovascular disease), as well as higher smoking intensity. Conclusions: Diabetes mellitus is associated with markedly poorer periodontal status, greater systemic disease burden, and increased prevalence of plaque-retentive local factors. These findings reinforce the bidirectional relationship between diabetes and periodontitis and support the integration of periodontal assessment into metabolic disease management protocols. Full article

Background/Objectives: Angiotensin-converting enzyme (ACE) inhibitors are commonly prescribed anti-hypertensive agents. However, one of their effects is reducing the breakdown of a number of pro-inflammatory mediators, including bradykinin and substance P. Given the role of inflammation in periodontal disease, the aim of this study was to see whether ACE inhibitors may have an influence on the severity of periodontal disease, as assessed by clinical attachment loss. Methods: A case–control retrospective study was undertaken through analysis of patient records from a specialist periodontic practice. Data regarding the loss of clinical attachment was collected from patients who were non-smokers and grouped according to patients prescribed ACE inhibitors, those taking other antihypertensive medication, and those taking no antihypertensive medication. Results: No statistically significant difference was observed between the three treatment groups in terms of mild to moderate loss of attachment (1–3 mm; 4–5 mm). However, a significantly higher incidence of severe attachment loss (>6 mm) was observed in patients prescribed ACE inhibitors, as compared to another antihypertensive or no antihypertensive medication. Conclusions: The incidence of severe loss of clinical attachment in this study was highest in those patients being prescribed ACE inhibitors. This effect would appear to be independent of the effects of the medication on blood pressure, since this was not observed with other antihypertensive medications, and hence may potentially relate to the known pro-inflammatory action of ACE inhibitors. Full article

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease characterized by chronic inflammation, extracellular matrix degradation, and smooth muscle cell apoptosis. Porphyromonas gingivalis (P. gingivalis), a key periodontal pathogen, has been implicated in the progression of cardiovascular diseases, including AAA, but the underlying mechanisms remain unclear. In this study, we investigated the role of GroEL, a bacterial heat shock protein 60 homolog derived from P. gingivalis, in AAA development. We employed a CaCl₂-induced AAA mouse model to evaluate the in vivo effects of GroEL. Mice received periaortic CaCl₂ application followed by intravenous injections of recombinant GroEL. Histological analyses were performed to assess aneurysmal dilation, elastin degradation, and inflammatory cell infiltration. Flow cytometry and immunohistochemistry were used to determine macrophage phenotypes, while cytokine profiles were quantified via ELISA. In vitro, THP-1 monocytes were treated with GroEL to evaluate its impact on macrophage polarization and cytokine expression. Our results showed that GroEL administration significantly enhanced aortic diameter expansion and elastin breakdown, accompanied by increased infiltration of M1-like macrophages and elevated levels of pro-inflammatory cytokines such as TNF-α and IL-6. In vitro findings confirmed that GroEL promotes M1 polarization and inhibits M2 marker expression in THP-1-derived macrophages. These findings suggest that P. gingivalis-derived GroEL plays a pathogenic role in AAA by modulating macrophage polarization toward a pro-inflammatory phenotype. Targeting microbial components such as GroEL may offer new therapeutic strategies for AAA management. Full article

Background: Psychological stress is increasingly recognized as a potential modifier of periodontal disease through both behavioral and biological mechanisms. Cortisol, a key stress hormone, exerts complex immunomodulatory effects and may influence periodontal inflammation and tissue breakdown. This study aimed to compare salivary levels of cortisol, interleukin-1β, and interleukin-6 in patients with varying periodontitis severity and examine their associations with clinical periodontal parameters. Methods: A total of 67 patients diagnosed with periodontitis were classified according to the 2017 World Workshop Classification into Stage I/II vs. Stage III/IV and Grade B vs. Grade C. Unstimulated saliva samples were collected and analyzed for cortisol using electrochemiluminescence immunoassay, and for IL-1β and IL-6 using ELISA. Statistical analyses included Mann-Whitney U test, Spearman’s correlations, and multivariate regression. Results: Median salivary cortisol levels were significantly higher in Stage III/IV (11.90 nmol/L) than in Stage I/II (7.64 nmol/L; p = 0.014) and in Grade C (10.60 nmol/L) vs. Grade B (7.70 nmol/L; p = 0.019). In multivariate analysis, cortisol independently predicted both Stage III/IV (OR = 1.23, p = 0.007) and Grade C (OR = 1.24, p = 0.026) periodontitis. ROC analysis showed that salivary cortisol had moderate diagnostic performance for Stage III/IV periodontitis (AUC = 0.68, cut-off 11.57 nmol/L) and Grade C (AUC = 0.67, cut-off 9.76 nmol/L). Cortisol showed significant positive correlations with clinical markers of disease severity and with IL-1β (r = 0.399, p = 0.001) and IL-6 (r = 0.424, p < 0.001). Conclusions: Salivary cortisol is a promising non-invasive biomarker reflecting both stress-related physiological burden and clinical severity in periodontitis. Cortisol measurement may represent a valuable addition to multifactorial assessments and risk stratification in periodontitis, pending further validation in longitudinal studies. Full article