We propose that calcitonin, secreted in response to the intake of food, aids in routing calcium, obtained by intestinal absorption, into bone fluid. Here calcium is temporarily stored in combination with phosphate for return to the extracellular fluid (blood) during intervals between oral intakes of calcium. The net result is a conservation of calcium postprandially and a decrease in parathyroid hormone-induced bone destruction during subsequent fasting periods. Evidence for this postulate is provided in the following six sequential steps from the time a calcium-containing meal is consumed until that portion of calcium stored in bone fluid is utilized during fasting periods to aid in plasma calcium maintenance. This labile storage form of calcium is the first to be utilized during fasting periods. In the absence of partial disruption of this storage mechanism, rapid development of pathological bone conditions would not be expected because PTH action permits the extended utilization of bone calcium for plasma calcium control. However, augmentation of osteopenic conditions could be expected if long-term low calcium intake were accompanied by a malfunction of this calcitonin-induced system for calcium storage.

Rats were raised after weaning on a vitamin Ddeficient diet which used whole wheat and casein as the major protein source. For at least the first year of life, plasma calcium concentrations of these rats were the same as those of vitamin Dreplete rats, and the rate of growth was normal for at least 6 months. The following evidence establishes the vitamin D deficiency of the rats (both male and female) on this diet: (i) plasma levels of 1,25-dihydroxycholecalciferol (1,25-dihydroxyvitamin D3) became undetectable after 6 weeks on the diet; (ii) by 4 months of age, the epiphyseal growth plates of the tibia were significantly enlarged and disorganized; (iii) when subjected to fracture in a dynamic torsion machine, the femur showed marked weakening as indicated by stress analysis; (iv) isolated kidney cells from the deficient rats showed a 3-fold increase in 25-hydroxyvitamin D 1-hydroxylase activity. When mother rats were placed on the vitamin D-deficient diet during lactation, plasma calcium values in the pups decreased and remained low throughout life and there was a stunted body growth pattern. It is concluded that hypocalcemia is not a necessary manifestation of vitamin D deficiency, that the onset of vitamin D deficiency during neonatal life influences the calcium homeostatic system, and that the normocalcemic, vitamin D-deficient animal provides an experimental model in which the effects of vitamin D deficiency can be studied independently of hypocalcemia.Prior to the availability of reliable assays for 1,25-dihydroxycholecalciferol [1,25-dihydroxyvitamin D3; 1,25-(OH)2D3], a deficiency in this vitamin in chicks and rats was identified by measuring the decrease in plasma calcium and phosphorus concentrations that resulted in time from the use of classical rachitogenic diets (1, 2). Various dietary manipulations such as the addition to the diet of large quantities of glucose (3) or manipulation ofthe calcium-to-phosphorus ratio (4) were usually used to give the desired end result-i.e., a low plasma calcium concentration, thereby indicating a deficiency of 1,25-(OH)2D3.The rat chow routinely provided animals to be used in all experiments by our research groups is that developed by Toverud and associates (5). This diet includes ground whole wheat and casein as protein sources with a total phosphorus content of0.4% in the form of organic phosphate. Normally, the calcium content is also 0.4% but can be varied from near zero to 1%. Recent studies in our laboratories required that both male and female rats be maintained for up to 1 year on a vitamin D-deficient diet. Therefore, the same diet, without vitamin D, was used. Data presented here provide evidence for the disassociation of hypocalcemia from vitamin D deficiency.

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