Differential effects of very high doses of doxercalciferol and paricalcitol on serum phosphorus in hemodialysis patients

Background: Treatment of secondary hyperparathyroidism (SHPT) includes use of calcitriol (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 due to gut absorption of calcium and phosphorus as well as enhanced bone resorption. The vitamin D analog 19-Nor-1,25(OH)₂-vitamin D₂ (paricalcitol) and the prohormone 1α-OH-vitamin D₂ (doxercalciferol) have been proposed as alternatives which may cause less hypercalcemia and elevated Ca × P, while still suppressing PTH. Methods: We performed a prospective study to assess th e acute bone mobilization effects of very high doses of paricalcitol and doxercalciferol. 13 hemodialysis patients received 160 mcg of paricalcitol and 120 mcg of doxercalciferol on 2 separate occasions in a research center while on a low calcium, low phosphorus diet, and sevelamer alone as a phosphorus binder. Changes in Ca, PO₄, and PTH were measured over 36 h. Results: Serum phosphorus rose faster, and pea ked significantly higher at 36 h following doxercalciferol (2.12 ± 0.11 mmol/l) than paricalcitol (1.85 ± 0.07 mmol/l; p = 0.025). Ca × P product also rose more following doxercalciferol than paricalcitol, and peaked higher at 36 h (5.02 ± 0.26 vs. 4.54 ± 0.21 mmol/l; p = 0.061). In contrast, suppression of PTH at 36 h was comparable (63% after paricalcitol and 65% with doxercalciferol). Conclusion: Consistent with animal studies, paricalcitol provides profound PTH suppression, while stimulating bone resorption and/or intestinal absorption less than doxercalciferol, resulting in less elevation of serum phosphorus and Ca × P.