Host-modulatory therapy in periodontitis: Role of subantimicrobial-dose doxycycline and beyond

Periodontitis is a chronic inflammatory disease in which tissue destruction results largely from an exaggerated host immune response to bacterial biofilms. Host-modulatory therapy (HMT) aims to control this destructive response and improve periodontal treatment outcomes. Among the various agents investigated, subantimicrobial-dose doxycycline (SDD) is the first and currently the only FDA-approved host-modulating drug used as an adjunct to conventional periodontal therapy. At low doses, doxycycline inhibits matrix metalloproteinases and reduces inflammatory mediators without exerting clinically significant antimicrobial effects. Clinical studies have demonstrated improved probing depth reduction and clinical attachment gain when SDD is used alongside scaling and root planing. Other host-modulatory approaches, such as non-steroidal anti-inflammatory drugs, bisphosphonates, specialised pro-resolving mediators, and chemically modified tetracyclines, have also been explored with varying levels of evidence. Although many of these agents show promising anti-inflammatory and bone-preserving effects, their routine clinical use remains limited. Host-modulatory therapy, therefore, represents an important adjunctive strategy in the comprehensive management of periodontitis.