Inhibitory effect of a novel bisphosphonate, TRK-530, on dental calculus formation in rats

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 micromoles/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.