Controlled Release of Osteoprotegerin: A Promising Additional Option for the Treatment of Apical Periodontitis with Intractable Periradicular Lesion

Introduction: It often takes a relatively long period for a tooth with a large periradicular lesion to recover from bone destruc-tion; therefore, it is necessary to develop additional approaches to serve as supplementary options to RCT. One possibility is to prevent the osteoclast-induced periapical bone destruction by inhibiting osteoclastogenesis. Recently, studies have proved the receptor activator of nuclear factor κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system to be an important signal pathway regulating osteoclastogenesis, and in-activation of RANKL, which blocks the RANK/RANKL pathways, is critical in anti-bone resorption.The hypothesis: OPG, a natural decoy receptor for RANKL, may be a potential clinical anti-resorptive agent for apical periodontitis. Since OPG can block the RANK/RANKL pathways, it has been demon-strated to be a good candidate against bone destruction; its local delivery through root canals may be an additional option for treatment of apical periodontitis with large periradicular lesion.Evaluation of the hypothesis: OPG is easy to produce, store and use. Using a large animal study model, recombinant OPG could be incorporated into degradable carriers such as microspheres, micelle, and deli-vered into experimental induced periradicular lesions in the animals by controlled release, where it can relieve bone destruction by inhibiting osteoclastogenesis and osteoclast function. As OPG is a natural protein and clinical delivery as part of RCT treatment is easy and simple, the application of OPG may provide a new avenue for the treatment of apical periodontitis with large periradicular lesion.