Differential effects of acute administration of 19-Nor-1,25-dihydroxy-vitamin D2 and 1,25-dihydroxy-vitamin D3 on serum calcium and phosphorus in hemodialysis patients.
BACKGROUND
Treatment of hyperparathyroidism includes the use of 1,25-dihydroxy-vitamin D3 (1,25D3) to suppress parathyroid hormone (PTH), but dosing of 1,25D3 is limited by the development of hypercalcemia and a high calcium x phosphorus (Ca x P) product because of gut absorption of calcium and phosphorus and enhanced bone resorption. The vitamin D analogue 19-nor-1,25(OH)2-vitamin D2 (19-Nor) causes less hypercalcemia and elevated Ca x P, whereas it still suppresses PTH in rats.


METHODS
To determine whether 19-Nor had similar effects in humans, we performed a prospective crossover study to assess bone mobilization. Ten hemodialysis patients on a low-calcium low-phosphorus diet were administered 20 microg of 1,25D3 and 120 and 160 microg of 19-Nor, and changes in calcium, phosphorus, and intact and whole PTH levels were measured over 36 hours.


RESULTS
Ca x P product increased more after 1,25D3 administration than after a six- or eightfold greater dose of 19-Nor and was significantly greater at 6, 12, and 24 hours. Ca x P product at 36 hours was 60.9 +/- 3.4 (4.91 +/- 0.27 mmol2/2) after 1,25D3 administration, 53.2 +/- 2.7 (4.29 +/- 0.22 mmol2/L2) after administration of 120 microg of 19-Nor, and 54.2 +/- 2.7 (4.37 +/- 0.22 mmol2/L2) after administration of 160 microg of 19-Nor. Suppression of intact PTH at 36 hours was similar after administration of 1,25D3 (54.1% +/- 6.0%) and 120 microg of 19-Nor (54.4% +/- 3.4%) and significantly greater after administration of 160 microg of 19-Nor (63.6% +/- 2.3%). The whole PTH assay yielded values approximately 25% to 30% lower than the intact PTH assay, and the percentage of suppression was virtually identical.


CONCLUSIONS
Consistent with animal studies, 19-Nor provides profound PTH suppression while stimulating bone resorption and/or intestinal absorption less than 1,25D3, resulting in less elevation of serum calcium and phosphorus levels.
Coyne
Daniel W
DW
Department of Internal Medicine, Renal Division, and the Chromalloy American Kidney Center at Washington University School of Medicine, St Louis, MO, USA. dcoyne@im.wustl.edu
Grieff
Marvin
M
Ahya
Shubhada N
SN
Giles
Karla
K
Norwood
Kathy
K
Slatopolsky
Eduardo
E
D000328:Adult; D000368:Aged; D001862:Bone Resorption / Q000378:metabolism; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000097:blood* / Q000378:metabolism; D018592:Cross-Over Studies; D004032:Diet; D004334:Drug Administration Schedule; D004872:Ergocalciferols / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors; D010758:Phosphorus / Q000097:blood* / Q000378:metabolism; D011446:Prospective Studies; D006435:Renal Dialysis / Q000379:methods*
D004872:Ergocalciferols; D010281:Parathyroid Hormone; D010758:Phosphorus; C084656:paricalcitol; D002117:Calcitriol; D002118:Calcium