24,25-dihydroxyvitamin D-3 in combination with 1,25-dihydroxyvitamin D-3 ameliorates renal osteodystrophy in rats with chronic renal failure

Aims: This study compares the effects of 1,25(OH)(2)D-3 and 24,25(OH)(2)D-3 alone or in combination on renal osteodystrophy in rats with chronic renal failure (CRF). Material and method: One month subsequent to 5/6 nephrectom y animals were divided into four groups and treated for one or four weeks w ith either vehicle, 1,25(OH)(2)D-3, 24,25(OH)(2)D-3 or 1,25(OH)(2)D-3 +24,2 5(OH)(2)D-3. A sham-operated group with normal renal function matched for a ge and weight was used as control. At the termination of the study blood ch emistry, parathyroid hormone (PTH) level and bone histomorphometry were ana lyzed. Results: The main findings were: amelioration of 1,25(OH)(2)D-3-indu ced hypercalcemia by 24,25(OH)(2)D-3, and similar suppression of PTH by the two metabolites of vitamin D when administered alone or in combination. Bo ne histomorphometry showed that 1,25(OH)(2)D-3 alone exerts a potent prolif erative effect on the osteoblasts but severely depresses their mineralizing capacity in a dose- and time-dependent manner. By contrast, 24,25(OH)(2)D- 3 improved the mineralizing activity with only a limited effect on osteobla st proliferation. Addition of 24,25(OH)(2)D-3 potentiated the beneficial ef fect of 1,25(OH)(2)D-3 on bone-resorbing parameters and corrected the miner alization failure. Conclusions: Based on the above observations we suggest that the combined treatment with 1,25(OH)(2)D-3 and 24,25(OH)(2)D-3 markedl y improves the morphologic and metabolic abnormalities of renal osteodystro phy.