24,25-dihydroxyvitamin D3 in combination with 1,25-dihydroxyvitamin D3 ameliorates renal osteodystrophy in rats with chronic renal failure.
OBJECTIVE
This study compares the effects of 1,25(OH)2D3 and 24,25(OH)2D3 alone or in combination on renal osteodystrophy in rats with chronic renal failure (CRF).


METHODS
One month subsequent to 5/6 nephrectomy animals were divided into four groups and treated for one or four weeks with either vehicle, 1,25(OH)2D3, 24,25(OH)2D3 or 1,25(OH)2D3 + 24,25(OH)2D3. A sham-operated group with normal renal function matched for age and weight was used as control. At the termination of the study blood chemistry, parathyroid hormone (PTH) level and bone histomorphometry were analyzed.


RESULTS
The main findings were: amelioration of 1,25(OH)2D3-induced hypercalcemia by 24,25(OH)2D3, and similar suppression of PTH by the two metabolites of vitamin D when administered alone or in combination. Bone histomorphometry showed that 1,25(OH)2D3 alone exerts a potent proliferative effect on the osteoblasts but severely depresses their mineralizing capacity in a dose- and time-dependent manner. By contrast, 24,25(OH)2D3 improved the mineralizing activity with only a limited effect on osteoblast proliferation. Addition of 24,25(OH)2D3 potentiated the beneficial effect of 1,25(OH)2D3 on bone-resorbing parameters and corrected the mineralization failure.


CONCLUSIONS
Based on the above observations we suggest that the combined treatment with 1,25(OH)2D3 and 24,25(OH)2D3 markedly improves the morphologic and metabolic abnormalities of renal osteodystrophy.
Gal-Moscovici
A
A
Nephrology and Hypertension Services, Hadassah University Hospital, Jerusalem, Israel.
Rubinger
D
D
Popovtzer
M M
MM
D015650:24,25-Dihydroxyvitamin D 3 / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002117:Calcitriol / Q000008:administration & dosage / Q000627:therapeutic use*; D002120:Calcium Channel Agonists / Q000627:therapeutic use*; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004359:Drug Therapy, Combination; D007676:Kidney Failure, Chronic / Q000150:complications*; D008297:Male; D051381:Rats
D002120:Calcium Channel Agonists; D015650:24,25-Dihydroxyvitamin D 3; D002117:Calcitriol