TY - JOUR
T1 - Effect of 24,25(OH)2D3 on PTH levels and bone histology in dogs with chronic uremia
AU - Olgaard, K.
AU - Finco, D.
AU - Schwartz, J.
AU - Arbelaez, M.
AU - Teitelbaum, S.
AU - Avioli, L.
AU - Klahr, S.
AU - Slatopolsky, E.
N1 - Funding Information:
This work was supported by the United States Public Health Service NIAMDD grants AM09976, AM07l26. and AMI1674. Dr. K. Olgaard was partly supported from the Danish Medical Research Council. The authors thank Dr. J. Lemann, Medical College of Wisconsin, for the determination of l,25(0H),D; Hoffman-LaRoche for supplying the 24,25(0H)2D-utilized in these sttidies; and Mrs. P. Verplancke for assistance in the preparation of this manuscript. The present address of Dr. K. Olgaard is the Nephrological Department P 2132, Rigshospitalet, Copenhagen. Denmark.
PY - 1984
Y1 - 1984
N2 - Controversy exists as to whether 24,25(OH)2D3 has a direct inhibitory effect on parathyroid hormone (PTH) secretion. Therefore, the present investigation examined the effect of long-term administration of 24,25(OH)2D3 on immunoassayable PTH levels (iPTH) and bone histology in dogs with chronic renal failure. Chronic renal failure was produced in 16 dogs, half of which served as controls whereas the other half received 2.5 μg/day of 24,25(OH)2D3, orally. Serum iPTH, serum total, ionized calcium, serum phosphorus, and creatinine were followed at weekly or biweekly intervals in both groups. Also, creatinine clearances, serum levels of 25(OH)D3, 24,25(OH)2D3, and 1,25(OH)2D3 and the intestinal absorption of calcium were measured. After 1 year of chronic renal failure the dogs were sacrificed and rib biopsy specimens were obtained for histological examination and measurement of mineral content. Serum iPTH increased equally in the 2 dog groups with no effect at any time of 24,25(OH)2D3 treatment, despite a significant increase in the serum levels of 24,25(OH)2D3 and a concomitant decrease of the 1,25(OH)2D3 levels. There was no difference in the levels of serum calcium or in the calcium content of bone. Furthermore, after 8 months of uremia 3 control dogs were switched to the group treated with 24,25(OH)2D3 and followed for another 7 months. No suppressive effect of administering 24,25(OH)2D3 on the iPTH levels could be demonstrated in these 3 dogs. On the rib biopsy specimens the number of osteoclasts was increased in the 24,25(OH)2D3-treated dogs, compared to the control uremic dogs and normal control dogs, indicating no inhibition by 24,25(OH)2D3 of the effect of PTH on bone. It is concluded that long-term treatment with 24,25(OH)2D3 alone in dogs with chronic renal failure has no effect either on the secretion or on the skeletal effects of PTH.
AB - Controversy exists as to whether 24,25(OH)2D3 has a direct inhibitory effect on parathyroid hormone (PTH) secretion. Therefore, the present investigation examined the effect of long-term administration of 24,25(OH)2D3 on immunoassayable PTH levels (iPTH) and bone histology in dogs with chronic renal failure. Chronic renal failure was produced in 16 dogs, half of which served as controls whereas the other half received 2.5 μg/day of 24,25(OH)2D3, orally. Serum iPTH, serum total, ionized calcium, serum phosphorus, and creatinine were followed at weekly or biweekly intervals in both groups. Also, creatinine clearances, serum levels of 25(OH)D3, 24,25(OH)2D3, and 1,25(OH)2D3 and the intestinal absorption of calcium were measured. After 1 year of chronic renal failure the dogs were sacrificed and rib biopsy specimens were obtained for histological examination and measurement of mineral content. Serum iPTH increased equally in the 2 dog groups with no effect at any time of 24,25(OH)2D3 treatment, despite a significant increase in the serum levels of 24,25(OH)2D3 and a concomitant decrease of the 1,25(OH)2D3 levels. There was no difference in the levels of serum calcium or in the calcium content of bone. Furthermore, after 8 months of uremia 3 control dogs were switched to the group treated with 24,25(OH)2D3 and followed for another 7 months. No suppressive effect of administering 24,25(OH)2D3 on the iPTH levels could be demonstrated in these 3 dogs. On the rib biopsy specimens the number of osteoclasts was increased in the 24,25(OH)2D3-treated dogs, compared to the control uremic dogs and normal control dogs, indicating no inhibition by 24,25(OH)2D3 of the effect of PTH on bone. It is concluded that long-term treatment with 24,25(OH)2D3 alone in dogs with chronic renal failure has no effect either on the secretion or on the skeletal effects of PTH.
UR - http://www.scopus.com/inward/record.url?scp=0021752494&partnerID=8YFLogxK
U2 - 10.1038/ki.1984.220
DO - 10.1038/ki.1984.220
M3 - Article
C2 - 6335904
AN - SCOPUS:0021752494
SN - 0085-2538
VL - 26
SP - 791
EP - 797
JO - Kidney International
JF - Kidney International
IS - 6
ER -