2-methylene-19-nor-20(S)-1alpha-hydroxy-bishomopregnacalciferol [20(S)-2MbisP], an analog of vitamin D3 [1,25(OH)2D3], does not stimulate intestinal phosphate absorption at levels previously shown to suppress parathyroid hormone.
Chronic kidney disease results in a reduction in 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) synthesis and an accumulation of phosphorus in the blood, leading to secondary hyperparathyroidism and renal osteodystrophy. Vitamin D analogs that retain the ability to suppress PTH but that are less calcemic and phosphatemic than the native hormone are preferred therapies for secondary hyperparathyroidism. However, even the most favored analog currently approved for the treatment of chronic kidney disease patients, i.e. 1,25-dihydroxy-19-nor-vitamin D2 (19-nor-D2, Zemplar), still retains some ability to stimulate intestinal absorption of calcium and phosphate. A recently described analog of vitamin D3, 2-methylene-19-nor-20(S)-1alpha-hydroxy-bishomopregnacalciferol [20(S)-2MbisP], suppresses PTH levels, but is unable to stimulate intestinal calcium absorption or bone resorption in rats. The present study shows that 20(S)-2MbisP is unable to stimulate intestinal phosphate absorption at levels known to suppress PTH secretion. Further, 19-nor-vitamin D2 under the same circumstances does stimulate phosphate absorption. Thus, 2MbisP has significant potential in the management of secondary hyperparathyroidism of renal failure.
Williams
Katie B
KB
Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin-Madison, 433 Babcock Drive, Madison, WI 53706, United States.
DeLuca
Hector F
HF
D000818:Animals; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007408:Intestinal Absorption; D008297:Male; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors*; D010710:Phosphates / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004100:Dihydroxycholecalciferols; D010281:Parathyroid Hormone; D010710:Phosphates; C521167:2-methylene-19-nor-(20S)-1 alpha-hydroxy-bishomopregnacalciferol