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 × 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.