Neural Modulation of Orthodontic Tooth Movement

Millions of people worldwide have orthodontic therapy for the treatment of dental malocclusions, craniofacial disorders, and simply to improve their appearance. However, orthodontic treatment has several major problems, including the long time braces must be worn, the pain involved during treatment, and the need to wear retainers to prevent relapse. Orthodontics could be improved. Understanding the mechanisms involved with orthodontic tooth movement represents a first step toward this goal. Improvements in the practice of orthodontics would have an immediate and significant impact on the millions of individuals undergoing orthodontic treatment worldwide. Orthodontic tooth movement can be thought of as an interaction of mechanical force on biological tissue (Krishnan and Davidovitch, 2006; Wise and King, 2008). Much progress in orthodontics has involved finding better means to apply mechanical force to teeth. While advances have been made regarding the mechanics and materials used in orthodontics, there has been a relative plateau in the overall treatment outcomes. For example, a moderately difficult case still requires an average of 18-36 months for treatment, no different than 50 years ago. It is apparent that discoveries relating to biological manipulations may provide a path for significantly improving orthodontic practice. It is thought that enhancing the speed of orthodontic tooth movement could be accomplished if bone remodeling occurred at an accelerated rate in the alveolar bone associated with the teeth being moved. While this has not been formally demonstrated in the clinic, animal studies strongly support this notion. For example, orthodontic tooth movement in a mouse model was accelerated by overexpressing Receptor Activator of Nuclear Factor Kappa B-Ligand (RANKL) (Kanzaki et al., 2006). RANKL promotes the formation and bone resorptive activity of osteoclasts, the specialized cells charged with bone resorption (Hofbauer and Heufelder, 2001). Conversely, inhibitors of osteoclast formation and activity including osteoprotegerin (OPG), integrin inhibitors, bisphosphonates and inhibitors of matrix metalloproteinases all slowed tooth movement (Holliday et al., 2003; Dolce et al., 2003; Kanzaki et al., 2004; Dunn et al., 2007). Although these studies showed that it is possible to manipulate the speed at which orthodontic tooth movement proceeds by altering osteoclast activity, the specific agents tested to date are probably inappropriate for orthodontic use in the clinic as there would be too much danger of off target effects. Such risks are unacceptable for orthodontic procedures. Although orthodontics as currently