Relative effectiveness of vitamin D metabolites in increasing bone mineral solubility

Abstract

Weanling rats were given a vitamin D-deficient diet containing 1.4% calcium and 1.0% phosphorus. After 4 weeks these deficient animals were injected for 7 days with selected doses of one of the following vitamin D metabolites: 25(OH)D3, 1,25(OH)2D3, 24,25(OH)2D3, 25,26(OH)2D3 or the ethanol vehicle. A vitamin D-replete group was placed on the same diet but injected with 50 IU of vitamin D3 once a week for the entire 5-week period. By the use of a modified Ussing chamber [1], the measurements of calcium fluxes into and from the rat calvaria were possible. These data enabled the apparent mineral solubilities to be derived. After 5 weeks on this diet the vitamin D-deficient rats had low levels of serum calcium (1.41 mM) and decreased mineral solubility when compared to the vitamin D-replete group. The apparent solubility of the bone mineral increased toward the vitamin D-replete level in calvaria from vitamin D metabolite-treated rats. However, these changes did not directly reflect the alterations in the level of serum calcium. At any given dose level, 1,25(OH)2D3 was the most effective metabolite in increasing serum calcium. In fact, the high dose (250 pmoles/day) was hypercalcemic. Next in effectiveness was 25(OH)D3. These two metabolites were equally effective in increasing mineral solubility. At a 10 times higher dose, the 24,25(OH)2D3 metabolite was able to normalize serum calcium and improve but not normalize mineral solubility. At the high dose (260 pmoles/day), the 25,26(OH)2D3 metabolite caused no effect on mineral solubility and minimal increases in serum calcium.

Food Contents and Biological Activity of 25-Hydroxyvitamin D: A Vitamin D Metabolite to Be Reckoned With?

“…Lastly, the concentration of 25OHD in serum is often reported to be better correlated with absorption of calcium from the intestine and a more important determinant of calcium absorption than is serum 1,25(OH) 2 D [5,6,63]. Thus, from these and other studies [7,51,64,65] it is apparent that 25OHD is capable of substituting for 1,25(OH) 2 D, however usually at higher doses than 1,25(OH) 2 D [4]. Relatively few studies have compared the activities of 25OHD with its parent form.…”

Studies of diffusion in calvaria

“…Previous experience [5,11] had shown that diphosphonate administration and vitamin D status have profound influence on the exchange-diffusion of phosphate and calcium, respectively. These experimental manipulations were therefore tested for their effect, or lack of effect, on simple diffusion processes.…”

“…After 4 weeks on the diet vitamin D deficiency was confirmed by decreased growth rate, low levels of serum calcium and of 25-hydroxyvitamin D3. Further data on these experimental animals have been published elsewhere [5]. One group received 10/~1 of ethanol/day for 7 days (vitamin D deficient); other groups received ethanol containing 1,25(OH)2D3 at 2.6 pmoles/day (low dose), 26 pmoles/day (medium dose), or 260 pmoles/day (high dose).…”