Bisphosphonates and nephrocalcinosis in a rabbit leg lengthening model: A histological and therapeutic comparison

We performed a comparison of the effects of two bisphosphonates, pamidronat e and zoledronic acid, on regenerate bone mineral content in distraction os teogenesis in an immature rabbit model. Single dose zoledronic acid was fou nd to be 18 times more potent at producing an increase in bone mineral cont ent than pamidronate per mg/kg of drug infused at surgery. Histological exa mination of all rabbit kidneys was performed at trial completion. Nephrocal cinosis was identified in 14 of 20 kidneys of rabbits infused with pamidron ate, but was not detected in the 20 kidneys of those rabbits infused with z oledronic acid. A further 20 kidneys from rabbits given a second dose of zo ledronic acid were also found to be free of signs of nephrocalcinosis. Thre e of 40 control kidneys exhibited signs of nephrocalcinosis. The increased potency of zoledronic acid allowed us to give one-tenth the dose of pamidro nate, with increased therapeutic efficacy and no evidence of nephrocalcinos is.