Objective : To evaluate the relationship between the dose of Clodronate and serum level of alkaline phosphatase (ALP), calcium (Ca), and phosphate (PO4) during orthodontic tooth movement MaterialS and MethodS: A total of 18 sex-matched Wistar rats (weight=180~230g, mean age=8 weeks) were allocated into the 2.5mM Clodronate (2.5C) group, 10mM Clodronate (10C) group, or control group (n=6 for each group). After the application of a nickel-titanium closed coil spring (force of 60g) between the upper central incisors and first molars (UFM), 2.5C, 10C, or saline was injected every third day into the subperiosteum of the alveolar bone adjacent to UFM for the experimental and control groups. The animals were sacrificed 17 days later. Trunk blood was quickly collected into a heparinized tube and centrifuged at 2,000 rpm for 20 min. The plasma was used for the biochemical assays of the serum level of ALP, Ca, and PO4. Kruskall-Wallis test and Mann-Whitney test with Bonferroni correction were performed for the statistical analyses. Results : Dose-dependent increase in the level of ALP (P<0.01) and decrease in the level of Ca (P<0.001) were observed among the control, 2.5C, and 10C groups. Although there was no significant difference in PO4 between the 2.5C and 10C groups, the 10C group showed a significantly higher level of PO4 than the control group (P<0.01). Conclusion : Since Clodronate induced significant dose-dependent change in the serum level of ALP, Ca, and PO4 during orthodontic tooth movement, orthodontists should consider these biochemical markers not only as a diagnostic tool for bone turnover rate but also as a monitoring tool for orthodontic tooth movement.