R B Mazess1, L Elangovan. 1. Bone Care International, Middleton, WI 53562, USA. rbmazess@facstaff.wisc.edu
Abstract
BACKGROUND/ METHODS: We examined 21 clinical trials (16 articles and 5 abstracts) that compared intravenous (i.v.) and oral vitamin D analogs for the treatment of secondary hyperparathyroidism in hemodialysis patients. Nearly all the studies had severe limitations, especially study size. Only 2 studies utilized more than 25 patients per treatment arm; 11 of the 16 articles and 4 of the 5 abstracts had less than 15 patients per arm. Calcitriol and/or alpha-calcidol were studied in 20 trials of the 21 studies (15 of the 16 articles) while 1 article examined doxercalciferol. RESULTS: No difference of efficacy between i.v. and oral dosing was found in 10 of the 15 articles in which efficacy was assessed. The i.v. route provided significantly faster suppression of elevated parathyroid hormone (PTH) and/or a greater degree of suppression in 5 of 15 applicable articles, but in 2 of these 5 studies the i.v. dose was substantially greater than the oral dose. Side effects, chiefly hypercalcemia, were noted in half of the articles. Six of 9 articles with detailed results found no significant difference; only 2 found significantly increased hypercalcemia with oral dosing, and 1 found significantly increased hypercalcemia with i.v. dosing. Only 3 articles reported on hyperphosphatemia and no difference was found for mode of administration. One factor influencing 19 of the 21 comparisons was the use of oral doses that were therapeutically equivalent to about half or less the i.v. dose given the lower bioavailability of oral D hormones. One larger study (70 patients) that compared equipotent dosing of the 2 administration routes found 4 times more hypercalcemia using oral than i.v. dosing (p < 0.001). Another factor complicating interpretation is that the treatment periods were short, with half being 16 weeks or less and only 2 lasting 36 weeks. CONCLUSION: Conclusions about the comparative efficacy and safety of the 2 administration routes require larger studies of longer duration that utilize therapeutically equivalent doses.
BACKGROUND/ METHODS: We examined 21 clinical trials (16 articles and 5 abstracts) that compared intravenous (i.v.) and oral vitamin D analogs for the treatment of secondary hyperparathyroidism in hemodialysis patients. Nearly all the studies had severe limitations, especially study size. Only 2 studies utilized more than 25 patients per treatment arm; 11 of the 16 articles and 4 of the 5 abstracts had less than 15 patients per arm. Calcitriol and/or alpha-calcidol were studied in 20 trials of the 21 studies (15 of the 16 articles) while 1 article examined doxercalciferol. RESULTS: No difference of efficacy between i.v. and oral dosing was found in 10 of the 15 articles in which efficacy was assessed. The i.v. route provided significantly faster suppression of elevated parathyroid hormone (PTH) and/or a greater degree of suppression in 5 of 15 applicable articles, but in 2 of these 5 studies the i.v. dose was substantially greater than the oral dose. Side effects, chiefly hypercalcemia, were noted in half of the articles. Six of 9 articles with detailed results found no significant difference; only 2 found significantly increased hypercalcemia with oral dosing, and 1 found significantly increased hypercalcemia with i.v. dosing. Only 3 articles reported on hyperphosphatemia and no difference was found for mode of administration. One factor influencing 19 of the 21 comparisons was the use of oral doses that were therapeutically equivalent to about half or less the i.v. dose given the lower bioavailability of oral D hormones. One larger study (70 patients) that compared equipotent dosing of the 2 administration routes found 4 times more hypercalcemia using oral than i.v. dosing (p < 0.001). Another factor complicating interpretation is that the treatment periods were short, with half being 16 weeks or less and only 2 lasting 36 weeks. CONCLUSION: Conclusions about the comparative efficacy and safety of the 2 administration routes require larger studies of longer duration that utilize therapeutically equivalent doses.