24-25-dihydroxyvitamin-d-3 and Calcinosis

Uraemic rats maintained on either a high or a low phosphate diet for 12 weeks were allocated to one of the following oral vitamin D treatment groups and received: 1,25-dihydroxycholecalciferol [1, 25-(OH)2D3], 24,25-dihydroxycholecalciferol [24,25-(OH)2D3], both 1,25-(OH)2D3 and 24,25-(OH)2D3, or no vitamin D supplements. Mean serum creatinine concentrations were elevated to a similar extent in all groups. Mean serum concentrations of calcium, phosphate and alkaline phosphatase were not significantly different from normal in any of the groups. In the group receiving the high phosphate diet and no vitamin D supplements, calcified bone area measured by quantitative computerized histomorphometry was significantly lower than in the group receiving the low phosphate diet and no vitamin D supplements (0.01 greater than P greater than 0.001), and in the groups receiving high phosphate diet and either 1,25-(OH)2D3 (0.01 greater than P greater than 0.001) or 24,25-(OH)2D3 (0.01 greater than P greater than 0.001). We conclude that uraemic rats maintained on a high phosphate diet for 12 weeks develop skeletal demineralization, this process does not occur in rats on a low phosphate diet, and a decrease in calcified bone area may be prevented by treatment with either 1,25-(OH)2D3 or 24,25-(OH)2D3.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Bone Diseases, Metabolic; Calcinosis; Calcitriol; Chronic Kidney Disease-Mineral and Bone Disorder; Creatinine; Dihydroxycholecalciferols; Male; Nephrectomy; Phosphates; Rats; Rats, Inbred Strains; Uremia

Severe hypokinesia of rats given the diet with a ratio of Ca:P = 1:0.5-1:3 was accompanied by hypocalcemia, development of osteoporosis, and some intensification of renal calcinosis. The decrease of phosphorus consumption (Ca:P = 1:0.5-1:1) prevented a development of these changes in intact animals and increased bone mineralization in hypokinetic ones. Excessive phosphorus consumption (Ca:P = 1:3) produced hypocalcemia, hyperphosphatemia, and some osteoporotic changes in the bones of intact animals and intensified these changes with hypokinesia. Administration of 24,25-dihydroxycholecalciferol, an active metabolite of vitamin D3, at a dose of 1.25 micrograms/d prevented a development of bone disorders, thus effectively stimulating diaphyses and epiphyses mineralization and correcting hypocalcemia in hypokinetic rats. 24,25(OH)2D3 at the same dose did not intensify nephocalcinosis and produced no toxic symptoms with hypokinetic animals.

Topics: 24,25-Dihydroxyvitamin D 3; Alkaline Phosphatase; Animals; Bone and Bones; Bone Diseases; Calcinosis; Calcium; Diet; Dihydroxycholecalciferols; Hypocalcemia; Kidney; Male; Osteoporosis; Phosphorus; Rats; Rats, Inbred Strains; Restraint, Physical