The appearance of osteoclasts at specific sites is the first step in bone remodeling, not only in orthodontic tooth movement but also in alveolar bone loss during periodontitis. Here, we review the two main approaches to antiresorptive therapy that have been developed during the last decades, and the recent discovery that periodontal ligament (PDL) cells might regulate osteoclastogenesis by opposite and different mechanisms such as receptor activator of NF-kappaB ligand (RANKL)’s stimulation and osteoprotegerin (OPG)’s inhibition. Since NF-kappaB is involved in the regulation of genes playing a positive role in osteoclast activity, the decoy approach to alter osteoclast development by inhibiting NF-kappaB action and its effects analyzed in terms of apoptosis is described. The above-mentioned approach significantly stimulates osteoclast apoptosis. The role of NF-kappaB decoy approach in avoiding bone resorption and the possibility of the development of new therapeutic strategies in orthodontics and in bone resorbing diseases like periodontitis is discussed
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