The effects of sustained delivery of alendronate on the kidney in ovariectomized female rats.

Bisphosphonates are indicated for the treatment and prevention of osteoporosis in adults; the treatment and prevention of glucocorticoid-induced osteoporosis; the treatment of Paget’s disease; and the treatment of multiple myeloma in patients with documented bone metastases. Two long-term trials in cancer patients demonstrated an increase in serum creatinine (SCr) when 8 mg of bisphosphonate was administered, prompting a recommendation to reduce the dose to 4 mg. The risk for renal toxicity remains a possibility following chronic administration of bisphosphonate treatment for osteoporosis. The goal of the study was to evaluate the kidney of osteoporotic female rats following chronic administration of alendronate using a drug delivery device for 4 weeks and compare the finding with control non-ovariectomized animals, ovariectomized control animals (OVX), and ovariectomized animals with an empty drug delivery system. The results of the study showed significant increases in body weights in the ovariectomized animals compared with non-ovariectomized animals. The organ wet-weights were not statistically different between the control and treatment groups or the ovariectomized and non-ovariectomized animals. Histological and histomorphometric analysis of the kidney revealed significant changes in the glomerular area on alendronate treated animals at 4 weeks when compared with ovx, ovx-sham and control non-ovariectomized animals. The results indicate chronic use of alendronate for osteoporosis may impair renal function or increase renal related problems in patients with existing kidney disease.