Effect of 24,25(OH)2D3 on PTH levels and bone histology in dogs with chronic uremia

Effect of 24,25(OH)2D3 on PTH levels and bone histology in dogs with chronic uremia. 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(OD)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 two 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 three 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 three dogs. On the rib biopsy specimens the number of osteoclasts was increased in the 24,25(OH)2D3-treated dogs, compared to 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. Effet de la 24,25(OH)2D3 sur les niveaux de PTH et l'histologie osseuse chez des chiens en urémie chronique. Il existe une controverse quant à un effet inhibiteur direct de la 24,25(OH)2D3 sur la sécrétion d'hormone parathyroïdienne (PTH). C'est pourquoi cette étude a examiné l'effet de l'administration à long terme de 24,25(OH)2D3 sur les niveaux de PTH dosables immunologiquement (iPTH) et sur l'histologie osseuse de chiens avec insuffisance rénale chronique. L'insuffisance rénale chronique a été provoquée chez 16 chiens, dont