24-25-dihydroxyvitamin-d-3 and Weight-Gain

Sex steroid hormones are known to have gender-dependent effects on bone and cartilage in vivo and in vitro. To investigate whether this is a general property of steroids, or is specific to the sex steroid hormones, we examined whether the effects on bone of 1,25-(OH)2D3 and 24,25(OH)2D3, the two active metabolites of vitamin D, are also gender-dependent. One-month-old male and female rats were treated for 1 month with various doses of 1,25-(OH)2D3, 24,25-(OH)2D3, or a combination of both metabolites. The direct effects of both metabolites on the skeleton of the treated animals were similar in male and female rats. 24,25-(OH)2D3 alone or in combination with 1,25-(OH)2D3 increased bone calcium and phosphorus, while 1,25-(OH)2D3 slightly decreased bone mineral content. 24,25-(OH)2D3 also enhanced the differentiation of cartilage in the growth plate, increasing the size of the hypertrophic zone. In addition, an increased metaphyseal bone volume was observed following 24,25-(OH)2D3 treatment in rats of both sexes, but not with 1,25-(OH)2D3. Vitamin D metabolites affected the weight gain of the experimental animals in a gender-dependent manner; 1,25-(OH)2D3 increased weight gain of male rats and 24,25-(OH)2D3 decreased weight gain of female rats. In addition, 1,25-(OH)2D3 increased bone weight and ash weight in male animals. These gender-dependent effects of vitamin D metabolites may occur indirectly via effects of sex steroid hormones, the latter being a sex-related effect.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Bone and Bones; Bone Density; Calcitriol; Calcium; Cartilage; Female; Male; Phosphorus; Rats; Rats, Wistar; Sex Characteristics; Vitamin D; Weight Gain

Glucocorticoids may induce osteopenia in experimental animals and in man. In order to study the possible effects of vitamin D metabolites in the prevention of glucocorticoid-induced osteopenia in rats, we administered 1 alpha(OH)-vitamin D3, 24,25(OH)2-vitamin D3 or a combination of both metabolites, by intragastric intubation, to rats treated daily by intramuscular injections of 10 mg/kg cortisone acetate. Treatment with the vitamin D metabolites started after 1 month of glucocorticoid therapy, at the time osteopenia was already present. Cortisone acetate decreased the gain weight, increased alkaline phosphatase (AP) and decreased Ca serum levels. It also decreased tibial wet and ash weight and tibial Ca content. Computerized histomorphometry of sections from the upper tibia showed decreased epiphyseal bone volume and increased bone marrow volume; decreased height of hypertrophic cartilage in the growth plate and decreased amount of persisting cartilage in the metaphyseal bone trabeculae were also observed. Administration of 24,25(OH)2D3 alone did not reduce these glucocorticoid-induced bone changes and sometimes even worsened them. 1 alpha(OH)D3 reversed many of the deleterious effects of cortisone acetate. It reduced serum AP levels, increased serum Ca levels, increased bone ash weight, epiphyseal and metaphyseal bone volume, with a concomitant reduction in epiphyseal and metaphyseal bone marrow volume. The best results were obtained by a combination of 1 alpha(OH)D3 and 24,25(OH)2D3. It is presumed that both metabolites are needed to reduce the impact of glucocorticoids on bone. 1 alpha(OH)2D3 acts on the gut, increasing Ca absorption (which was decreased by glucocorticoids), and 24,25(OH)2D3 directly acts on bone to enhance bone formation and mineralization.

Topics: 24,25-Dihydroxyvitamin D 3; Alkaline Phosphatase; Animals; Bone Density; Bone Diseases, Metabolic; Calcium; Female; Glucocorticoids; Hydroxycholecalciferols; Magnesium; Phosphorus; Radiography; Rats; Weight Gain

Changes in skeletal mass, nutritional calcium and phosphorus balance, and intestinal calcium absorption were studied in four groups of rats: control, exercise allowing free access to food, exercise with pair-feeding to control levels, and immobilization. The exercise regimen consisted of treadmill running 25 m/min, 60 min/day, 5 days/wk for 13 wk; rats were immobilized by bilateral sciatic denervation. The total body Ca (TBCa) was measured by neutron activation analysis as an index of skeletal mass. Standard metabolic balance techniques were used to determine calcium and phosphorus balance, and an in situ duodenal loop ligation preparation was used to study the active and passive intestinal Ca transport processes. Exercise promoted a positive Ca and P balance and increased the skeletal mass, largely as a result of an increase in 1,25-dihydroxyvitamin D and an enhancement of the intestinal Ca absorption efficiency. Urinary excretion of Ca and P did not differ from control levels and food intake was not a factor because pair-fed rats responded to exercise almost identically to those fed ad libitum. Conversely, immobilization caused a decrease in TBCa and a lower Ca and P balance. These effects are the result of an increased urinary mineral excretion, greater endogenous fecal excretion, and decreased mineral absorption efficiency in the intestine.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Biological Transport; Biological Transport, Active; Calcitriol; Calcium; Dihydroxycholecalciferols; Feces; Female; Intestinal Absorption; Phosphates; Phosphorus; Physical Conditioning, Animal; Rats; Rats, Inbred Strains; Weight Gain