Dose- and time-dependent effects of clodronate on orthodontic tooth movement

Abstract

Orthodontic tooth movement is the result of bone remodeling that occurs in periodontal ligament and alveolar bone tissue as a response to mechanical loading of the tooth. The aim of this study is to investigate the time- and dose-response effects of locally administered clodronate on tooth movement. Sixty Wistar rats were randomly assigned to 4 groups of 15 specimens: E1 - application of 10 mMol of clodronate in 3-day intervals; E2 - application of 2.5 mMol of clodronate in 3-day intervals; E3 - application of 10 mMol of clodronate in 7-day intervals; E4 - application of 2.5 mMol of clodronate in 7-day intervals. A 50 μL clodronate solution was injected into a subperiosteal area to the right maxillary incisor. The left maxillary incisor served as a control, with an injection of saline solution. In 3-day interval application regime, there was no effect of clodronate dosing on tooth movement. In 7-day interval application regime, decreased tooth movement was observed with 10 mMol compared with 2.5 mMol clodronate concentration. However, decreased tooth movement was also observed when 2.5 mMol of clodronate was applied in 7-versus 3-day intervals. Conversely, no difference was observed when 10 mMol concentration was applied in 3- versus 7-day intervals. When clodronate is applied subperiosteally in the root area, it decreases the tooth movement. Tooth movement is impeded by the higher clodronate dosing, as well as by shorter application interval even with lower dosing. The purpose of future trials should, therefore, be to determine a safe therapeutic dose/interval application of clodronate in humans and their potential side effects.

FIGURE 1

Measurements of tooth movements. Tooth movements were calculated by measuring the distance between incisors (the middle of the distoproximal surface of incisors 2 mm from the gingiva) and molars (the middle of the mesioproximal ridge of the first molar) in the treated and control side. The measured distance between determined points on the incisor and molars represents bilaterally tooth movement in millimeters.

FIGURE 2

Osteoclasts in alveolar bone (immunohistochemistry, anti-calcitonin antibody, clone CAL-3-F5, ×400). Cells were considered osteoclasts if they were multinucleated and located on, or close to bone surfaces.