Pleiotropy of chemically modified tetracycline in periodontitis

Sir,

The current layout for the biological domain map of chronic periodontitis indicates that the bacterial challenge activates immuno-inflammatory response, due to which a complex interplay of several matrix metalloproteinases (MMPs), cytokines, and prostaglandin (PGE₂) activates and appear to destroy extracellular matrix material and activate bone resorption.[1] Host modulation therapy (HMT) is a strategy to reduce tissue destruction and stabilize the periodontium by modifying or downregulating destructive aspects of the host response and upregulating protective or regenerative responses is a recent and novel concept in periodontal therapy.[2] Chemically modified tetracycline (CMT), a non-antimicrobial modified tetracycline with versatile anti-inflammatory properties but potent host-modulating effects, is an excellent agent for the management of periodontitis. CMTs were produced by removing the dimethylamino group from the carbon-4 position of the A ring of the four-ringed (A, B, C, D) tetracycline structure. The resulting compound, 4-de-dimethyl amino tetracycline (CMT-1), did not have antimicrobial property, but the anti-collagenase activity was retained both in vitro and in vivo.[3] The main advantage of CMTs over the conventional tetracyclines is that long-term systemic administration does not cause gastrointestinal toxicity and higher plasma concentrations can be obtained with less frequent administration regimens.

CMTs combat to periodontitis via prevention of connective tissue breakdown through inhibition of metal-dependant MMPs, suppression of neutrophils, and inhibition of generation of arachidionic acid metabolites by blocking the phospholipase A₂ and PGE₂ synthesis, scavenging the reactive oxygen species, enhancing the attachment of fibroblasts and connective tissues to the tooth surface, and hence regenerating lost periodontium.[4] Currently, sub-antimicrobial dose doxycycline (SDD) and minocycline have been established as effective HMT. Various researches in the literature has proposed the beneficial effects of adjunctive HMT without surgery in the management of periodontist.[5] Recent studies have demonstrated superior therapeutic role of SDD in combination with access flap debridement for improvement of post-operative wound healing and periodontal health in chronic periodontitis. Other accumulating evidences revealed successful management of periodontal disease in patients with postmenopausal osteoporosis (decrease bone mass condition). Nevertheless, various biomarkers in gingival cervicular fluid (e.g., collagen telopeptide fragments) were found to reduce in subjects following SDD dosing. The field of “perioceutics,” or the use of pharmacological agents, specifically developed to better manage periodontitis, is emerging to aid in the management of susceptible patients who are sub-optimally responding to the conventional therapy for periodontal disease.