Saturation of the Biological Response to Orthodontic Forces and Its Effect on the Rate of Tooth Movement

Objectives: The objectives of this research are to investigate the biological response of the body to different magnitude of force, and to investigate if the response varies among individuals. Therefore this research has 3 Specific Aims: Aim 1 is to investigate the biological response to different magnitudes of orthodontic forces at molecular and cellular levels in animals; Aim 2 is to investigate whether an equal magnitude of force can stimulate different levels of biological response among individuals; Aim 3 is to investigate whether the limit of biological response to different magnitudes of orthodontic force varies among individuals. Methods and Materials: For Aim 1, different magnitudes (0 to 100 cN) of constant, continuous force were applied on the maxillary first molar of Sprague Dawley rats. The maxillae were collected for RNA and protein analysis, immunohistochemistry, and micro CT at different time points. For Aim 2, human subjects in different age groups (age 11-14 and 21-45) were recruited. Canine retraction was rendered with a constant force of 50 cN, and gingival crevicular fluid (GCF) was collected at different time points up to 28 days after retraction. The activity of inflammatory markers in GCF including IL-1β, CCL2, TNF-α, RANKL, and MMP-9 were measured using protein arrays. The rate of canine retraction in 28 and 56 days was measured on study models. For Aim 3, human subjects in different age groups (same as Aim 2) were recruited. Each subject in both age groups was randomly assigned to receive certain magnitude of constant force (50 to 200 cN) for canine retraction. The activity of different inflammatory markers in GCF one day after retraction was measured using protein arrays. The rate of canine retraction in 28 days was measured on study models. Results: In the animal study, there was a linear relation between the force and the level of cytokine expression at lower magnitudes of force. Higher magnitudes of force did not increase the expression of cytokines. Activity of CCL2, CCL5, IL-1, TNF, RANKL, and number of osteoclasts reached a saturation point in response to higher magnitudes of force, with unchanged rate of tooth movement. In the clinical studies, activities of IL-1β, CCL2, TNF-α, RANKL, and MMP-9 increased significantly one day after retraction in both age groups. Inflammatory marker activities were significantly higher in adults compared with adolescents at 50-cN force. However, the rate of tooth movement was greater in adolescents than adults during the 56-day study period. At higher force magnitudes, the inflammatory marker activities were higher in adolescents than adults. Both age groups demonstrated saturation in biological response, with higher saturation point in adolescents than adults. Conclusion: 1. After a certain magnitude of force, there is a saturation in the biological response, where higher magnitude of force does not increase inflammatory markers, osteoclasts, nor amount of tooth movement. Therefore, higher forces to accelerate the rate of tooth movement are not justified and other methods should be considered. 2. The level of biological response varies among individuals to an identical magnitude of force. Therefore, one should compare the level of biological response within the same individual. 3. Saturation of biological response to higher magnitude of orthodontic force exists in both rats and humans, and the saturation point varies among individuals. Adolescents exhibit higher saturation point than adults. Therefore it is not justified to apply higher magnitudes of force in adults