Evidence for the promotion of bone mineralization by 1alpha,25-dihydroxycholecalciferol in the rat unrelated to the correction of deficiencies in serum calcium and phosphorus.
Concurrent administration of 1alpha,25-dihydroxycholecalciferol [1alpha,25-(OH)2-CC] to intact and thyroparathyroidectomized rats treated with ethane-1-hydroxy-1,1-diphosphonate (EHDP) prevented or reversed the EHDP-induced inhibition of bone mineralization as measured by changes in epiphyseal plate width and ash content of bone. An analog, 1alpha-droxycholecalciferol, was also effective. Recovery of bone after EHDP treatment was also significantly improved by administration of 1alpha,25-(OH)2-CC as evidenced by enhanced uptake of 45Ca by epiphyseal plates and decreased plate widths. Cholecalciferol (CC), ergocalciferol, dihydrotachysterol2, 5,6-trans-CC, 25-OH-CC, 5,6-Trans-25-OH-CC, and 1alpha24R,25-(OH)3-CC also blocked EHDP-induced epiphyseal plate widening, but required high, pharmacological dose levels. 24R,25- (OH)2-CC was inactive at doses up to 10 microgram/day. Since EHDP-treated rats are not deficient in calcium or phosphate, these data suggest that 1alpha,25-dihydroxycholecalciferol promoted bone mineralization independently of effects upon the intestinal absorption of calcium and phosphate.
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002113:Calcification, Physiologic / Q000187:drug effects; D002118:Calcium / Q000378:metabolism* / Q000627:therapeutic use; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D004838:Epiphyses / Q000378:metabolism; D012968:Etidronic Acid / Q000494:pharmacology*; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D006996:Hypocalcemia / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D010280:Parathyroid Glands / Q000502:physiology; D010758:Phosphorus / Q000378:metabolism* / Q000627:therapeutic use; D051381:Rats; D013961:Thyroid Gland / Q000502:physiology
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D010758:Phosphorus; D012968:Etidronic Acid; D002118:Calcium