Effect of 1α-Hydroxyvitamin D₃ in Rats with Experimental Renal Osteodystrophy

Abstract

A model of experimental renal osteodystrophy was established in the rats with chronic renal failure induced by partial nephrectomy and therapeutic effects of 1α-hydroxyvitamin D₃ (1α-OH-D₃) were studied. Male Wistar rats weighing 180g were 5/6 nephrectomized and fed a normal diet (Ca and P: 1%) for 6 months. After the surgery, serum creatinine levels increased 60% and thereafter continued to rise gradually with their growth for 4 to 5 months, followed by rapid increase. The serum phosphorus levels were also elevated concomitantly and the serum calcium concentrations were normal. Marked bone resorption accompanied with hypertrophy of parathyroid glands was observed by histological examinations (Tetrachrome-Fuchsin stain, contact microradiography and H-E stain). The bone resorption seemed to be due to secondary hyperparathyroidism.
Treatment with 0.25μg/kg/day p.o. of 1α-OH-D₃ for 10 days in the uremic state resulted in remarkable new bone formation which was confirmed by histological examinations. These results clearly demonstrated that the reduction of nephron mass play a critical clue of renal osteodystrophy and 1α-OH-D₃ appears to have a good potential for clinical use in patients with renal failure and metabolic bone diseasses