OBJECTIVE: To examine possible ultrastructural alterations in the kidneys caused by bisphosphonate administration, and to investigate whether bisphosphonates could cause irreversible alterations to the kidneys in healthy individuals. STUDY DESIGN: Ten female Wistar rats were randomly divided into 2 groups: experimental and control. The experimental rats received bisphosphonate for 13 weeks, after which the animals were sacrificed and kidney specimens were studied with optic and electronic microscope. RESULTS: Our results support the hypothesis that bisphosphonate treatment results in ultrastructural alterations in the rat kidney. It remains to be elucidated whether these are related to a specific clinical picture and whether they show remission after withdrawal. CONCLUSION: Monitoring serum creatinine prior to and during treatment and probably temporarily withholding therapy in the setting of renal insufficiency in patients with preexisting chronic kidney disease can be very helpful in order to avoid further nephrotoxicity in these cases. © Science Printers and Publishers, Inc.