A METHOD OF EXTENDING THE DOSE RANGE OF VITAMIN D COMPOUNDS

摘要

Inhibitors of bone calcium resorption are administered, and calcium intake in the subject's diet is restricted, to allow high doses of vitamin D compounds or mimetics to be given with the intent of treating diseases such as metabolic bone diseases, hyperparathyroidism, cancer, psoriasis, and autoimmune diseases without the dangers of calcification of kidney, heart, and aorta. Inhibitors of bone calcium resorption include the bis-phosphonates, OPG (osteoprotegerin) or the soluble RANKL (receptor activator of NF-?B ligand) receptor known as sRANK (soluble RANK which is the protein expressed by the NF-?B gene), and function to block the availability of calcium from bone thereby preventing hypercalcemia and the resulting calcification of soft tissues. Thus, high doses of la,25-dihydroxyvitamin D3 (1,25-(OH)2D3), its analogs, prodrugs, or mimetics can be utilized to treat the target disease with minimal risk to a patient. Specifically, alendronate is shown to block the bone calcium mobilization activity of both 1,25-(OH)2D3 and its very potent analog, 2-methylene-19-nor-(20S)-la,25-dihydroxyvitamin D3, as long as the subject being treated is on a low calcium diet.