SURGICALLY INDUCED UREMIA IN RATS .1. EFFECT ON BONE STRENGTH AND METABOLISM

During the course of chronic renal failure (CRF) in man, renal osteody strophy (osteitis fibrosa and/or osteomalacia) gradually develops. The present study aimed to establish a similar type of CRF leading to ren al osteodystrophy in rats. During progressive CRF development over 225 days after 5/6 nephrectomy, the following serum variables were measur ed: creatinine, immunoreactive parathryoid hormone (iPTH), 1,25-dihydr oxyvitamin D-3 (1,25(OH)(2)D-3), a25-hydroxyvitamin D-3, (25(OH)D-3), alkaline phosphatase, albumin, phosphate, urea nitrogen, total calcium , and other blood electrolytes. Subsequent to sacrifice, mechanical pr operties of the rat femur, bone histomorphometry (osteoid and eroded s urfaces) and bone contents of calcium, phosphate and hydroxyproline we re also examined. Serum creatinine in rats with CRF gradually escalate d by some 70%, while circulating 1,25(OH)(2)D-3 was reduced beneath de tection level. Total plasma calcium and phosphate concentrations were, however, almost unchanged indicating that PTH-induced bone remodeling due to moderate hyperparathyroidism sustained calcium homeostasis. Al kaline phosphatase levels were reduced by some 50%, which reflects chr onically impeded bone formation. Bone histomorphometry assessment reve aled substantial elevation of resorption with moderate accompanying fi brosis in about 70% of afflicted animals. Bone calcium, phosphate and hydroxpyroline contents remained unaltered. However, hydroxoproline/ca lcium ratio was marginally reduced. These results, together with alter ed mechanical bending stress characteristics and diminished diaphysis cross section area, confirm development of mixed bone lesions in the u remic animals. Our results are compatible with the early development o f CRF in man. The established rat model is therefore useful in elucida ting the precipitation and early treatment of renal osteodystrophy in humans.