ALENDRONATE INHIBITS OSTEOPONTIN EXPRESSION ENHANCED BY PARATHYROID HORMONE-RELATED PEPTIDE (PTHRP) IN THE RAT-KIDNEY

It has been reported that osteopontin (OPN) plays an important role du ring urolithiasis as well as bone formation. Generation of stones in t he urinary tract may be associated with osteoporosis and bisphosphonat es are potent inhibitors of bone resorption, being used with effect in the management of bone disease. We therefore investigated the relatio nship between alendronate, a bisphosphonate derivative, and OPN expres sion in the kidney. Alendronate was administered to rats made hypercal cemic by treatment with parathyroid hormone-related peptide (PTHrP). T he renal expression of OPN was then evaluated at both protein and mRNA levels. OPN expression was enhanced in the distal tubular cells of hy percalcemic rats and was decreased by alendronate. The observed inhibi tion of OPN expression suggests an ability of alendronate and other bi sphosphonates to act as inhibitors of stone formation in the urinary t ract.