Relative effectiveness of vitamin D metabolites in increasing bone mineral solubility.

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)D, 1,25(OH)D, 24,25(OH)D, 25,26(OH)D or the ethanol vehicle. A vitamin D-replete group was placed on the same diet but injected with 50 IU of vitamin D 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)D 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)D. These two metabolites were equally effective in increasing mineral solubility. At a 10 times higher dose, the 24,25(OH)D 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)D metabolite caused no effect on mineral solubility and minimal increases in serum calcium. [ABSTRACT FROM AUTHOR]