TY - JOUR
T1 - 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
AU - Coyne, Daniel W.
AU - Grieff, Marvin
AU - Ahya, Shubhada N.
AU - Giles, Karla
AU - Norwood, Kathy
AU - Slatopolsky, Eduardo
N1 - Funding Information:
Supported in part by the General Clinical Research Center at Washington University (US Public Health Service grant no. MO1 RR00036) and grants from Abbott Pharmaceuticals and Genzyme Corp.
PY - 2002/12/1
Y1 - 2002/12/1
N2 - 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 × phosphorus (Ca × 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 × 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 μg of 1,25D3 and 120 and 160 μg of 19-Nor, and changes in calcium, phosphorus, and intact and whole PTH levels were measured over 36 hours. Results: Ca × 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 × P product at 36 hours was 60.9 ± 3.4 (4.91 ± 0.27 mmol2/L2) after 1,25D3 administration, 53.2 ± 2.7 (4.29 ± 0.22 mmol2/L2) after administration of 120 μg of 19-Nor, and 54.2 ± 2.7 (4.37 ± 0.22 mmol2/L2) after administration of 160 μg of 19-Nor. Suppression of intact PTH at 36 hours was similar after administration of 1,25D3 (54.1% ± 6.0%) and 120 μg of 19-Nor (54.4% ± 3.4%) and significantly greater after administration of 160 μg 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. Conclusion: 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.
AB - 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 × phosphorus (Ca × 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 × 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 μg of 1,25D3 and 120 and 160 μg of 19-Nor, and changes in calcium, phosphorus, and intact and whole PTH levels were measured over 36 hours. Results: Ca × 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 × P product at 36 hours was 60.9 ± 3.4 (4.91 ± 0.27 mmol2/L2) after 1,25D3 administration, 53.2 ± 2.7 (4.29 ± 0.22 mmol2/L2) after administration of 120 μg of 19-Nor, and 54.2 ± 2.7 (4.37 ± 0.22 mmol2/L2) after administration of 160 μg of 19-Nor. Suppression of intact PTH at 36 hours was similar after administration of 1,25D3 (54.1% ± 6.0%) and 120 μg of 19-Nor (54.4% ± 3.4%) and significantly greater after administration of 160 μg 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. Conclusion: 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.
KW - Hemodialysis (HD)
KW - Hyperparathyroidism (HPT)
KW - Vitamin D
UR - http://www.scopus.com/inward/record.url?scp=0036895239&partnerID=8YFLogxK
U2 - 10.1053/ajkd.2002.36899
DO - 10.1053/ajkd.2002.36899
M3 - Article
C2 - 12460048
AN - SCOPUS:0036895239
SN - 0272-6386
VL - 40
SP - 1283
EP - 1288
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 6
ER -