Chronic adaptation of dog parathyroid function to a low-calcium-high-Sodium-Vitamin D-deficient diet

Abstract

The development of secondary hyperparathyroidism was studied in relation to changes in serum ionized Ca (Ca2+), 25-OHD, and 1,25-(OH)2D concentrations in six dogs maintained on a low-Ca (0.05%), high-Na (1.6%), and vitamin D-deficient diet for 91 weeks. Blood samples and evaluations of the parathyroid function were obtained before and after 3, 12, 24, 36, and 91 weeks of diet. Serum iPTH was measured by an intact hormone (I) and a carboxy-terminal (C) assay. The sigmoidal relationship between ionized Ca and iPTH values was evaluated mathematically. Results are means +/- SD. Statistically significant changes over a time period were evaluated by an ANOVA for repeated measurements. Over the first 3 weeks, serum Ca2+, 25-OHD, and 1,25-(OH)2D did not change but stimulated I-iPTH increased 84.3 +/- 39.9% (p less than 0.005) and C-iPTH only 25.3 +/- 12.2% (p less than 0.01), a significant difference (p less than 0.02). The increase in stimulated I-iPTH reached 487.4 +/- 139.6% (p less than 0.0001) and 418.4 +/- 76.9% (p less than 0.0001) for C-iPTH by the end of the study. Similar significant increases were seen in basal and nonsuppressible iPTH at or after week 12.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of Secondary Hyperparathyroidism Induced by Low Dietary Calcium, Vitamin D Deficiency, and Renal Failure on Circulating Rat PTH Molecular Forms

“…C/T-rPTH rose because of greater C-rPTH than T-rPTH increment possibly due to the catabolism of secreted rPTH(1-84) into C-rPTH fragments. This differs from our dog model of D deficiency where % PTH(1-84) was increased [1, 28], but the latter study was of two-year duration. A slightly longer study might have provided a calcemic dissociation between -Ca and -D diets.…”

“…A negative correlation was observed between 25(OH)D and 1,25(OH) 2 D levels. Hypocalcemia was best explained by reduced intestinal absorption of calcium induced by low 1,25(OH) 2 D [32, 33] in relation to very low substrate concentrations [1]. The latter is probably the consequence of deficient vitamin D supply [1].…”

“…Hypocalcemia was best explained by reduced intestinal absorption of calcium induced by low 1,25(OH) 2 D [32, 33] in relation to very low substrate concentrations [1]. The latter is probably the consequence of deficient vitamin D supply [1]. rPTH levels were elevated because of hypocalcemia and low 1,25(OH) 2 D, both of which stimulated rPTH production via different mechanisms [34–36].…”

“…In experimental calcium and vitamin D-deficient dogs, ionized calcium remains unchanged until 1,25(OH) 2 D starts to decline after an initial increment. This behavior was attributed to 25(OH)D levels dipping below 20 nmol/L [1]. Furthermore, as sHPT progresses, basal, stimulated, and nonsuppressible Intact (I) PTH increases more than carboxyl-terminal (C) PTH levels, indicating a shift in PTH secretion toward PTH(1-84) [1].…”

“…This behavior was attributed to 25(OH)D levels dipping below 20 nmol/L [1]. Furthermore, as sHPT progresses, basal, stimulated, and nonsuppressible Intact (I) PTH increases more than carboxyl-terminal (C) PTH levels, indicating a shift in PTH secretion toward PTH(1-84) [1]. When these dogs were replenished with vitamin D, ionized calcium and 25(OH)D normalized rapidly while 1,25(OH) 2 D initially reached supraphysiological values which progressively regressed to normal with time [2].…”