Background: The effects of bisphosphonates on prophylaxis of stone formation are unclear. We evaluated the outcome of two new-generation bisphosphonates in a lithogenic rat model. Methods: 36 male rats were divided into three groups of 12 animals each. Both calcium and creatinine levels of plasma and urine were measured. Zinc discs of about 40 mg each were surgically placed into the bladder. The first group received no treatment and the second and third groups were treated with an intraperitoneal injection of weekly clodronate (20 mg/kg) and zoledronic acid (7.5 µg/kg), respectively. At the end of the 8th week, the weight increase in discs and biochemical changes were analyzed comparatively. Results: The mean weight of discs in the control, clodronate and zoledronic acid groups was 109.65 ± 80.97, 79.82 ± 17.99 and 72.91 ± 19.29 mg, respectively (p > 0.05). The percentage increase in weight of discs was 164% for control, 90% for clodronate and 71% for the zoledronic acid group. The increase of urinary calcium level in the zoledronic acid group was lower than the others (p < 0.05). Conclusions: When considering the percentage increase in weight of discs, the difference between control and bisphosphonate groups support the idea that these drugs may have a preventive role in stone formation.

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