Inhibitory Effect of a Novel Bisphosphonate, TRK-530, on Dental Calculus Formation in Rats M.N. Haq Sikder Division of Dental Anesthesiology, Department of Oro-Maxillofacial Surgical Science, Tohoku University Graduate School of Dentistry, Sendai, Japan.
Masatoshi Itoh Basic Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa, Japan.
Naofumi Iwatsuki Division of Dental Anesthesiology, Department of Oro-Maxillofacial Surgical Science, Tohoku University Graduate School of Dentistry, Sendai, Japan.
Dr. Hisashi Shinoda Division of Dental Pharmacology, Department of Oral Biology, Tohoku University Graduate School of Dentistry.
Background: A newly developed bisphosphonate, TRK-530 (disodium dihydrogen[4-(methylthio)phenylthio]methanebisphosphonate), has recently been reported to show anti-inflammatory and anti-bone-resorbing activity. Since bisphosphonates have been shown to inhibit the formation of calcium-phosphate crystals in vitro, TRK-530 may inhibit the formation of dental calculus. Therefore, the present study was performed to examine whether this compound has such an effect.
Methods: Three groups of Wistar rats fed a calculogenic diet (RC16) were treated with TRK-530 in drinking water at concentrations of 0 (control group), 0.75, and 1.5 mM. Another group received a daily subcutaneous injection of TRK-530 at a dose of 2.25 µmoles/rat, which was assumed to correspond to the maximum amount of this compound absorbed from the intestine when rats received 1.5 mM TRK-530 in drinking water. Rat dental calculus formation was evaluated. The crystalline nature of dental calculus was studied by x-ray diffraction analysis. Finally, the effects of TRK-530 on the precipitation of calcium-phosphate from solution were tested in vitro.
Results: TRK-530 in drinking water inhibited dental calculus formation dose-dependently. However, subcutaneous injection of TRK-530 did not have any significant effect, suggesting that the anticalculus effect of TRK-530 in drinking water was topical, not systemic. The calculus that formed in both the control and experimental groups was primarily hydroxyapatite, a main constituent of human dental calculus. TRK-530 inhibited the precipitation of calcium-phosphate from solution in vitro.
Conclusions: TRK-530 inhibited the formation of dental calculus in a dose-dependent fashion via a local effect. Inhibition of the precipitation of calcium-phosphate from solution might be involved in the anticalculogenic mechanism of this drug. J Periodontol 2004;75:537-545.
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