Salivary RANKL/OPG and Periodontal Status Among Users of Heated Tobacco and Electronic Cigarettes Versus Non-Smokers: A Prospective Observational Study

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.