Investigation of the possibilities for host modulation therapy for periodontal treatment

Abstract

Background: Periodontitis is a globally prevalent chronic inflammatory disease characterized by immune dysregulation and alveolar bone loss. Conventional therapies, while effective in many cases, often fail to achieve complete resolution, particularly in patients with systemic comorbidities or aggressive disease phenotypes. This has led to increasing interest in Host Modulation Therapy (HMT), which targets the underlying immunopathogenesis rather than the microbial component alone. Aim: This thesis investigates the potential of HMT in periodontal care, focusing on bonemodulating cytokines and the RANK/RANKL/OPG axis. It seeks to evaluate the feasibility of repurposing denosumab, a monoclonal antibody against RANKL used in osteoporosis, as a therapeutic adjunct in periodontitis. Methods: Two research questions were addressed. First, salivary concentrations of OPG, RANKL, and inflammatory cytokines (IL-1β, IL-6, IL-8, TNFα) were analysed in systemically healthy individuals with varying periodontal status (health, gingivitis, periodontitis) before and after treatment. Second, an exploratory clinical study assessed periodontal changes in a patients initiating denosumab therapy. Biomarker quantification was performed using multiplex immunoassays, and clinical inflammation was assessed using the Periodontal Inflamed Surface Area (PISA) metric. Results: OPG was variably detectable across health and periodontal disease states, while RANKL levels were consistently below detection thresholds. IL-1β showed a consistent reduction following treatment, suggesting its potential as a marker of therapeutic response. In the sample studied there were no significant correlations between cytokine levels and PISA. The denosumab study was limited by recruitment challenges and evolving prescribing guidelines, but provided valuable insights into the complexities of studying biologic agents in dental populations. Conclusion: HMT represents a promising adjunctive strategy in periodontal therapy, particularly for high-risk individuals. While current evidence supports the biological plausibility of targeting host pathways, further research is needed to validate targets, optimise delivery systems, and establish long-term clinical efficacy. The integration of personalised medicine and biomarker-guided care may enhance the future role of HMT in periodontal practice