Introduction: Periodontitis is a chronic inflammatory disease that leads to progressive destruction of periodontal tissues and eventual tooth loss, significantly affecting the patient’s quality of life. Dysregulated mechanistic target of rapamycin (mTOR) signaling contributes to periodontitis pathogenesis by influencing inflammation, autophagy, senescence, and bone metabolism. Rapamycin, a well-established mTOR inhibitor with geroprotective properties, has emerged as a promising therapeutic candidate in mitigating periodontal inflammation and preserving alveolar bone. Objective: This scoping review systematically synthesizes preclinical and clinical evidence on rapamycin’s effects on periodontal structures and disease etiopathogenesis, evaluating its potential as a therapeutic intervention for periodontitis. Methods: A systematic literature search was conducted in PubMed to identify studies evaluating rapamycin’s effect on periodontal health. Eligible studies were characterized into in vitro, animal, and clinical studies in terms of study design and research focus. Results: From 122 screened studies, 53 met inclusion criteria (18 in vitro, 21 in vivo, and 9 clinical). In vitro studies demonstrated that rapamycin enhances osteogenic differentiation, upregulates autophagy, suppresses inflammatory cytokines, and delays cellular senescence. Animal studies confirmed rapamycin’s role in alveolar bone preservation, inhibition of biofilm formation, immune modulation, and periodontal inflammation attenuation. Clinical studies primarily focused on rapamycin’s effects on gingival overgrowth in transplant recipients, with limited data on periodontitis outcomes. However, survey data from off-label rapamycin users reported improved periodontal health and reduced caries. Conclusion: Rapamycin exerts a multifaceted role in periodontal health by regulating autophagy, osteogenesis, inflammation, microbial composition, and cellular senescence. Given the U.S. Food and Drug Administration’s approval of rapamycin for other conditions, well-designed clinical trials are needed to establish its efficacy, optimize dosing strategies, and ensure long-term safety for periodontal therapy. Knowledge Transfer Statement: The findings highlighted in this scoping review can help researchers understand the potentially mechanistic pathways of rapamycin on periodontal tissues and guide future research on the therapeutic potential of rapamycin for the treatment of periodontitis.
Joshi et al. (Sat,) studied this question.