Effects of Etidronate Disodium on Crystallizations in Synthetic Urine and Calcium Oxalate Crystal Adhesion to Madin‐Darby Canine Kidney (MDCK) Cells

Background: 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. Methods: 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. Results: 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. Conclusion: 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.