Aggressive periodontitis (AgP) represents a rapidly progressive and highly destructive periodontal disorder characterized by severe alveolar bone loss, dysregulated host response, and pronounced inflammatory tissue breakdown disproportionate to the amount of microbial biofilm present. Traditional periodontal therapy has largely focused on mechanical removal of pathogenic biofilm; however, overwhelming evidence now supports the concept that host inflammatory dysregulation, rather than bacterial quantity alone, plays a central role in the pathogenesis of aggressive periodontitis. Host-modulation therapy (HMT) aims to counteract destructive inflammatory mediators, restore homeostasis, and improve outcomes when used adjunctively with conventional mechanical debridement. Various pharmacologic and biologic agents have been explored as host-modulating strategies, including subantimicrobial-dose doxycycline (SDD), nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, omega-3 polyunsaturated fatty acids, lipoxins, probiotics, and novel cytokine-targeting molecules. This article evaluates the effectiveness, clinical relevance, and therapeutic potential of host-modulation therapy in the management of aggressive periodontitis based on available literature. The present expanded review synthesizes contemporary knowledge regarding the pathogenesis of aggressive periodontitis, mechanisms of host-modulating agents, clinical outcomes, limitations, and future directions. Through an extensive analysis of the literature, the paper highlights the multidimensional value of host-modulation therapy and its role in optimizing periodontal healing when used as an adjunct to nonsurgical or surgical interventions.
