Indirect Inhibition of the Biosynthesis of 1,25-Dihydroxycholecalciferol in Rats Treated with a Diphosphonate

Abstract

1. Rats treated with disodium ethane-1-hydroxy-1,1-diphosphonate for 14 days developed rickets and impaired intestinal calcium transport, even when receiving large amounts of cholecalciferol (vitamin D3). 2. Vitamin d-deficient rats treated with the diphosphonate, and irrespective of the duration of such treatment, responded initially to a single intravenous dose of cholecalciferol with a normal production of 1,25-dihydroxycholecalciferol. 3. This normal response was followed within 2 days by an apparent inhibition of the renal biosynthesis of 1,25-dihydroxycholecalciferol. It is inferred that the impaired intestinal transport of calcium, in diphosphonate-treated rats receiving vitamin D, is due to a deficiency of this renal metabolite. 4. Inhibition of the synthesis of 1,25-dihydroxycholecalciferol could not be attributed to a direct action of the drug on the renal 1-hydroxylase, but appeared to be determined by the initial normal response to vitamin D. 5. The mechanisms possibly involved in producing this effect are discussed.