Differential effects of 19-nor-1,25-(OH)2D2 and 1α-hydroxyvitamin D2 on calcium and phosphorus in normal and uremic rats

Abstract

Calcitriol, 1,25-(OH)(2)D(3) (1,25D), the most active metabolite of vitamin D, has been used in the treatment of secondary hyperparathyroidism (SH) because it controls parathyroid gland growth and suppresses parathyroid hormone (PTH) synthesis and secretion. Due to the calcemic and phosphatemic actions of 1,25D, two analogs with potentially less side effects, 19-nor-1,25-(OH)(2)D(2) (19-nor) and 1alpha(OH)D(2) (1alphaD(2)) are currently being used in the treatment of SH. This study compares the effects of these two analogs on calcium (Ca) and phosphorus (P) metabolism in normal, uremic, and parathyroidectomized (PTX) rats. Using doses of 50 to 250 ng of 19-nor or 1alphaD(2), experiments were conducted in normal and uremic rats. In uremic rats, 19-nor did not increase plasma Ca or P while 1alphaD2 caused a dose-dependent increase in both. In addition, while the Ca x P product remained unchanged in 19-nor-treated rats, it increased progressively with 1alphaD(2)administration. In metabolic studies in normal rats treated with vehicle, 10 ng of 1,25D, 100 ng of 19-nor or 100 ng 1alphaD(2), intestinal calcium absorption and urinary calcium excretion were significantly higher in 1alphaD(2)-treated rats compared to those receiving 19-nor. Similar results were seen for intestinal phosphorus absorption and urinary phosphorus excretion. Finally, the skeletal response to these two analogs was tested in PTX rats fed a calcium-deficient diet and treated daily with 100 ng of 19-nor or 1alphaD(2). The increase in plasma calcium in 1alphaD2-treated rats was markedly higher than in those receiving 19-nor. Similar results were seen in plasma phosphorus when these studies were repeated using a phosphorus-deficient diet. These studies demonstrate that when given in large doses to rats 19-nor is less calcemic and phosphatemic than 1alphaD(2). The lower Ca x P product in 19-nor treated rats may be an important consideration in patient therapy. Further studies in patients are necessary to define the clinical applicability of these differences.