BIOCHEMICAL BONE MARKERS, BONE-MINERAL CONTENT, AND BONE-MINERAL DENSITY IN RATS WITH EXPERIMENTAL NEPHROTIC SYNDROME

The human nephrotic syndrome (NS) is accompanied by important alterati ons of mineral and bone metabolism. The purpose of the present study w as to examine bone metabolism in rats with experimental NS and normal creatinine clearance, and to evaluate the reversibility of this altera tion. NS was induced by three injections of puromycin aminonucleoside (PAN) on days 0, 21, and 35 (10, 5, and 5 mg/100 g body weight, respec tively). The biochemical markers of bone formation (osteocalcin and al kaline phosphatase) and bone resorption (hydroxyproline and pyridinoli ne), bone mineral content (BMC), and bone mineral density (BMD), deter mined by dual-energy x-ray absorptiometry (DEXA), were studied on days 0, 7, 24, 28, 42, 56, 84, and 112. Proteinuria was present throughout the study. Hypoproteinemia was seen on days 7, 28, 42, and 56, return ing to control values on days 84 and 112. In serum, osteocalcin (OC) c oncentration increased (p < 0.001), and alkaline phosphatase (ALP) dec reased (p = 0.002). In urine, hydroxyproline increased (p < 0.001), bu t urinary pyridinoline was not different from the control group throug hout the study. Increased serum parathyroid hormone concentration and decreased levels of 25-hydroxy and 1,25-dihydroxyvitamin D were found from day 7. During the intense proteinura, bone resorption predominate s and decreased BMC and BMD ensues in PAN-nephrotic rats. PAN-nephroti c rats showed low BMC and BMD compared to control group (p < 0.001). A t the end of the study, when proteinuria persisted but total serum pro tein returned to control values, the biochemical bone markers, BMC, an d BMD returned to normal. In conclusion, PAN-nephrotic rats had revers ible bone alterations that were related to the magnitude of proteinuri a and the concentration of total serum protein.