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

被引:37
作者
Slatopolsky, E [1 ]
Cozzolino, M [1 ]
Finch, JL [1 ]
机构
[1] Washington Univ, Sch Med, Dept Internal Med, Div Renal, St Louis, MO 63110 USA
关键词
secondary hyperparathyroidism; PTH; uremia; calcitriol analogs; vitamin D; chronic renal failure; hemodialysis;
D O I
10.1046/j.1523-1755.2002.00573.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background. 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. Methods. 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. Results. In uremic rats, 19-nor did not increase plasma Ca or P while 1alphaD(2) 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 1alphaD(2) -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. Conclusions. 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.
引用
收藏
页码:1277 / 1284
页数:8
相关论文
共 53 条
[1]   A NOVEL VITAMIN-D3 ANALOG, 22-OXA-1,25-DIHYDROXYVITAMIN-D3, INHIBITS THE GROWTH OF HUMAN BREAST-CANCER INVITRO AND INVIVO WITHOUT CAUSING HYPERCALCEMIA [J].
ABE, J ;
NAKANO, T ;
NISHII, Y ;
MATSUMOTO, T ;
OGATA, E ;
IKEDA, K .
ENDOCRINOLOGY, 1991, 129 (02) :832-837
[2]   A SYNTHETIC ANALOG OF VITAMIN-D3, 22-OXA-1-ALPHA,25-DIHYDROXYVITAMIN-D3, IS A POTENT MODULATOR OF INVIVO IMMUNOREGULATING ACTIVITY WITHOUT INDUCING HYPERCALCEMIA IN MICE [J].
ABE, J ;
TAKITA, Y ;
NAKANO, T ;
MIYAURA, C ;
SUDA, T ;
NISHII, Y .
ENDOCRINOLOGY, 1989, 124 (05) :2645-2647
[3]   INTRAVENOUS CALCITRIOL IN THE TREATMENT OF REFRACTORY OSTEITIS FIBROSA OF CHRONIC RENAL-FAILURE [J].
ANDRESS, DL ;
NORRIS, KC ;
COBURN, JW ;
SLATOPOLSKY, EA ;
SHERRARD, DJ .
NEW ENGLAND JOURNAL OF MEDICINE, 1989, 321 (05) :274-279
[4]   New therapies raise new issues for lowering parathyroid hormone levels in uremic patients [J].
Andress, DL .
SEMINARS IN DIALYSIS, 1999, 12 (05) :282-284
[5]  
[Anonymous], USRDS 1999 ANN DAT R
[7]   EFFECTS OF A NOVEL VITAMIN-D ANALOG MC-903 ON CELL-PROLIFERATION AND DIFFERENTIATION INVITRO AND ON CALCIUM-METABOLISM INVIVO [J].
BINDERUP, L ;
BRAMM, E .
BIOCHEMICAL PHARMACOLOGY, 1988, 37 (05) :889-895
[8]   Re-evaluation of risks associated with hyperphosphatemia and hyperparathyroidism in dialysis patients: Recommendations for a change in management [J].
Block, GA ;
Port, FK .
AMERICAN JOURNAL OF KIDNEY DISEASES, 2000, 35 (06) :1226-1237
[9]  
Bloembergen W E, 1997, Adv Ren Replace Ther, V4, P185
[10]  
BROWN AJ, 1994, SEMIN NEPHROL, V14, P156