EC Dental Science

Periodontitis is a chronic, multifactorial inflammatory disease characterized by dysbiosis of the subgingival biofilm, immune system activation, and progressive destruction of the periodontal tissues. Bacterial components (PAMPs) trigger recruitment and activation of macrophages, neutrophils, and lymphocytes, leading to the release of pro-inflammatory cytokines, reactive oxygen species, and matrix metalloproteinases (MMPs). These mediators drive osteoclastogenesis, alveolar bone resorption, and periodontal tissue breakdown. External systemic and local risk factors further exacerbate inflammation and disease progression. This review examines a therapeutic approach that remains underexplored: the preservation of bone structure and the periodontal ligament through modulation of immune-inflammatory pathways. Particular attention is given to clodronate, an atypical non-aminobisphosphonate with distinct pharmacological properties, including low affinity for hydroxyapatite, high biocompatibility with gingival tissues, and the ability to inhibit vesicular ATP storage and release in activated immune cells. Through these mechanisms, clodronate reduces cytokine expression, MMP activity, osteoclast activation, and the formation of neutrophil extracellular traps (NETs). Unlike other bisphosphonates, clodronate does not accumulate excessively in bone and presents minimal risk of jaw osteonecrosis, while also exhibiting unique analgesic effects. Its combined anti-inflammatory, anti-resorptive, and MMP-inhibitory actions suggest that clodronate may serve as a valuable adjunct to conventional periodontal therapies aimed at limiting inflammation, preserving alveolar bone, and improving long-term clinical outcomes.

Keywords:Periodontitis; Alveolar Resorption; Inflammation; Bisphosphonates

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