Effects of AMD3100 on Orthodontic Tooth Movement After Local/Systemic Administration

Objectives: To elucidate the effects of serial local versus systemic administration of CXCR4 antagonist AMD3100 on orthodontic tooth movement (OTM) in rats.
Methods: Six-week-old male Wistar/ST rats were randomly divided into the three groups. The control (n=6) animals were treated with phosphate-buffered saline, while the local (n=5) and systemic (n=6) animals were injected with AMD3100 at buccal and palatal mucosa adjacent to the maxillary right first molar (M1, 1,000 μM; 0.25 mg/kg; 0.1ml) and subcutaneously (1,000 μM; 5 mg/kg; 2ml), respectively. The M1 was moved mesially using a 10-g force nickel-titanium closing coil spring. The injections were performed every other days; at day 0, 2, 4, 6, 8, 10 and 12, respectively. On day 0, 1, 3, 7 and 14 after tooth movement, OTM distance and alveolar bone were examined by micro-computed tomography and histological analysis.
Results: OTM was significantly decreased in the local and systemic groups compared with the control group in every observed periods; day 1, 3, 7 (p<0.01) and 14 (local, p<0.05; systemic, p<0.01). There’s no significant difference on the amount of OTM between local and systemic administration. For the alveolar bone analysis, trabecular thickness (Tb.Th) and trabecular spacing (Tb.Spac) significantly increased and trabecular number (Tb.N) significantly decreased in the systemic group compared with the control group (p<0.05). Local injection also affected bone quality in the same way as systemic injection without significant difference between groups.
Conclusions: Despite using fewer doses of AMD3100, serial local administration of AMD3100 inhibited OTM. It also affected bone properties and osteoclast accumulation similar with systemic administration. These findings suggested that local administration of AMD3100 was effective in alveolar bone metabolism during OTM via inhibition of SDF-1/CXCR4 axis with less systemic side effect and higher cost effectiveness compared with systemic administration.