Increased intestinal absorption of calcium in young and adult x-linked hypophosphatemic mice after the administration of 1,25-dihydroxyvitamin D3

Abstract

We have reported that X-linked hypophosphatemic (Hyp) and normal mice respond equally to the administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] with uptake of 45Ca from an oral test meal as judged by the isotope remaining in the fecal samples. To determine whether this was due to specific stimulation of calcium absorption, as opposed to changes in calcium secretion or transit time, 1,25(OH)2D3 was administered to 4-week-old (young) and 13-week-old (adult) normal and Hyp mice at a dose of 0.12 micrograms/kg per day by continual infusion from an Alzet minipump. After 3 days of infusion, absorption of 45Ca from the isolated duodenum was measured in situ. Malabsorption of calcium was shown in vehicle-treated 4-week-old Hyp mice by significantly more 45Ca remaining in the intestinal segment and by significantly reduced plasma levels and reduced skeletal levels of 45Ca. Treatment of the young mice, both normal and Hyp, with 1,25(OH)2D3 resulted in increased absorption of 45Ca, increased plasma 45Ca, and increased incorporation of 45Ca into the femur. The young Hyp mice treated with 1,25(OH)2D3 showed a significant increase in femoral ash weight. At 13 weeks of age both normal and Hyp vehicle-treated mice showed equivalent absorption of calcium, and both responded to 1,25(OH)2D3 administration with enhanced calcium absorption. At both ages plasma phosphate rose in only the Hyp mice treated with 1,25(OH)2D3, whereas plasma and urine calcium were increased in only the hormone-treated normal mice. In conclusion, 1,25(OH)2D3 stimulates the absorption of calcium in the isolated duodenum of the young Hyp mouse with equal potency to that of young normal mice.