Sub-Antimicrobial Dose Doxycycline as a Host-Modulating Agent in the Management of Periodontitis: A Comprehensive Review

ABSTRACT Periodontitis is a chronic inflammatory disease characterized by progressive destruction of the supporting structures of the teeth, including gingiva, periodontal ligament, and alveolar bone. Although microbial plaque biofilm is considered the primary etiological factor initiating periodontal disease, the severity of tissue destruction largely depends on the host immune inflammatory response. Conventional periodontal therapy primarily focuses on mechanical removal of bacterial plaque through procedures such as scaling and root planning. However, this approach alone may not sufficiently control host-mediated inflammatory destruction. Consequently, host modulation therapy has emerged as an important adjunctive strategy in periodontal treatment. Sub-antimicrobial dose doxycycline (SDD) is currently the most extensively studied host-modulating pharmacologic agent used in periodontology. When administered at low doses that do not produce antibacterial activity, doxycycline demonstrates anti-inflammatory and anti-collagenase properties. The drug primarily inhibits matrix metalloproteinases, a group of enzymes responsible for degradation of connective tissue components in periodontal disease. In addition, SDD reduces inflammatory cytokine production, decreases osteoclast activity, and limits oxidative stress within periodontal tissues. Numerous clinical studies have demonstrated that SDD used in combination with conventional periodontal therapy results in improvements in clinical attachment level, probing pocket depth, and overall periodontal stability. This review provides a comprehensive overview of the pathogenesis of periodontitis, the principles of host modulation therapy, mechanisms of action of subantimicrobial dose doxycycline, clinical evidence supporting its therapeutic use, safety profile, limitations, and future perspectives in host-directed periodontal therapy. Keywords: Periodontitis; Sub-antimicrobial dose doxycycline; Host modulation therapy; Matrix metalloproteinases; Periodontal inflammation; Scaling and root planning; Connective tissue degradation; Adjunctive periodontal therapy.