Normocalcemia without hyperparathyroidism in vitamin D-deficient rats

Abstract

Despite numerous attempts, no reliable dietary regimen exists to achieve vitamin D deficiency (-D) in rats without attendant changes in plasma parathyroid hormone (PTH), Ca, or phosphate. This represents an important obstacle to proper investigations of the physiologic role(s) of vitamin D metabolites in the function of 1,25-dihydroxyvitamin D₃ [1,25-(OH)₂D₃] target tissues. This paper describes the successful development of such a diet, which uses a combination of high Ca content, properly controlled Ca/P ratio, and lactose. Normal weanling rats were fed diets containing A, 0.8% Ca, 0.5% P, +D₃, or -D diets containing B, 0.8% Ca and 0.5% P; C, 2.0% Ca and 1.25% P; or D, 2.0% Ca, 1.25% P, and 20% lactose. After 6 diet weeks group D rats remained normocalcemic and normophosphatemic, but diet groups B and C became hypocalcemic (6.9 ± 0.8 and 7.2 ± 0.4 mg/dl, respectively). Thus high dietary Ca and P was incapable of maintaining normal plasma Ca levels in the absence of dietary lactose. The normocalcemia in group D was not maintained by elevated PTH secretion because N-terminal PTH levels were also normal (14 ± 3 versus 20 ± 5 pg/ml). In contrast, PTH levels were markedly elevated in hypocalcemic groups B and C (47 ± 7 and 48 ± 10 pg/ml, respectively). Plasma 25-OHD₃ and 1,25-(OH)₂D₃ levels were reduced to < 120 and < 12 pg/ml, respectively, in all -D groups. Thus the high-Ca diet and the use of normal weanlings did not impede the development of vitamin D deficiency. This rat model of normocalcemic vitamin D deficiency will greatly facilitate elucidation of the physiologic role(s) of vitamin D metabolites in the normal functioning of 1,25-(OH)₂D₃ targets.