Ebisuno S, Kohjimoto Y, Nishikawa T, Nishihata M, Inagaki T, Komura T, Ohkawa T
Division of Urology, Minami Wakayama National Hospital, Japan.
Int J Urol. 1998 Nov;5(6):582-7. doi: 10.1111/j.1442-2042.1998.tb00416.x.
Several reports in the 1970s suggested that etidronate disodium might be clinically useful to prevent calcium stones, but the use of etidronate in the urolithiasis field was discontinued due to adverse effects of this drug on skeletal turnover and mineralization. Because the drug might affect not only crystallization, but also crystal-tubular interactions, we investigated the minimum dose of etidronate necessary to effectively prevent stone recurrence without adverse side effects.
We examined the effect of etidronate on the crystallization of calcium oxalate, calcium phosphate and magnesium ammonium phosphate using synthetic urine and measured by an aggregometer. We also studied its effect on the adhesion of calcium oxalate monohydrate crystals to Madin-Darby canine kidney (MDCK) cells in vitro.
Etidronate affected the crystallization+ of not only calcium phosphate and calcium oxalate, but also magnesium ammonium phosphate in synthetic urine. The inhibitory activities on these crystallizations were detected at extremely low drug concentrations. Etidronate also had a strong inhibitory activity against the adhesion of calcium oxalate crystals to MDCK cells.
Although further studies are necessary regarding the effects of etidronate on crystallization and crystal adhesion both in vivo and in vitro, and the appropriate schedule of dosing to prevent side effects, it is possible that etidronate may be useful in the treatment of urinary stones.
20世纪70年代的几份报告表明，依替膦酸二钠在临床上可能对预防钙结石有用，但由于该药物对骨骼周转和矿化的不良影响，其在尿路结石领域的使用已停止。由于该药物可能不仅影响结晶，还影响晶体与肾小管的相互作用，我们研究了有效预防结石复发且无不良副作用所需的依替膦酸最低剂量。
我们使用合成尿液，通过凝聚仪检测依替膦酸对草酸钙、磷酸钙和磷酸镁铵结晶的影响。我们还在体外研究了其对一水合草酸钙晶体与Madin-Darby犬肾（MDCK）细胞粘附的影响。
依替膦酸不仅影响合成尿液中磷酸钙和草酸钙的结晶，还影响磷酸镁铵的结晶。在极低的药物浓度下即可检测到对这些结晶的抑制活性。依替膦酸对草酸钙晶体与MDCK细胞的粘附也具有很强的抑制活性。
尽管关于依替膦酸在体内和体外对结晶及晶体粘附的影响，以及预防副作用的适当给药方案仍需进一步研究，但依替膦酸可能对尿路结石的治疗有用。
