Differential effects of 1,25-(OH)2D3 and 22-oxacalcitriol on phosphate and calcium metabolism.
1,25-dihydroxyvitamin D3 has been used with success in the treatment of secondary hyperparathyroidism associated with chronic renal failure. However, frequently 1,25-(OH)2D3 induces hypercalcemia, especially in those patients ingesting large doses of calcium carbonate, precluding the administration of therapeutic doses of 1,25-(OH)2D3. In addition, control of serum phosphorus is a persistent problem in patients maintained on chronic hemodialysis and 1,25-(OH)2D3 treatment can aggravate the hyperphosphatemia. Thus, ideally an analog of 1,25-(OH)2D3 that can suppress PTH with minor effects on calcium (Ca) and phosphate (PO4) metabolism would be an ideal tool to control secondary hyperparathyroidism. We have shown that 22-oxa-1,25-(OH)2D3 (OCT), an analog of 1,25-(OH)2D3 with little calcemic activity, can suppress PTH mRNA in normal rats and in cultured bovine parathyroid cells with equipotency to 1,25-(OH)2D3. To further characterize the differential effects of 1,25-(OH)2D3 and OCT on Ca and PO4 metabolism we performed several experiments in intact and parathyroidectomized (PTX) rats. In metabolic studies in four groups of normal rats 1,25-(OH)2D3 treatment (8 ng/day) significantly increased the intestinal Ca absorption from 15.2 +/- 2.68% to 30.5 +/- 2.85% (P < 0.01), while the same dose of OCT had no effect. A dose of 200 ng/day of OCT increased intestinal Ca absorption similarly to the 8 ng/day dose of 1,25-(OH)2D3, from 10.6 +/- 2.49% to 24.8 +/- 2.35% (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Finch
J L
JL
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Brown
A J
AJ
Kubodera
N
N
Nishii
Y
Y
Slatopolsky
E
E
D000818:Animals; D002117:Calcitriol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D005260:Female; D006934:Hypercalcemia / Q000139:chemically induced / Q000517:prevention & control; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010710:Phosphates; D002117:Calcitriol; C051883:maxacalcitol; D002118:Calcium