VITAMIN-D METABOLITES PREVENT VERTEBRAL OSTEOPENIA IN OVARIECTOMIZED RATS

The present study investigated the prophylactic effects of vitamin D metabolites and vitamin D metabolite combinations on static and dynamic, tetracycline-based, histomorphometric parameters in the axial skeleton of ovariectomized rats. Forty-three Fischer-344 rats (10 weeks old, 130 g each body weight, BW) were either bilaterally ovariectomized (OVX) or sham-operated (SHAM). The rats were allocated into the following groups: SHAM; OVX; OVX + 7.5 ng 1-alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]/rat/day; OVX + 15 ng 1-alpha,24R,25-trihydroxyvitamin D3 [1,24,25-(OH)3D3]/rat/day; OVX + 75 ng 24R,25-dihydroxyvitamin D3 [24,25(OH)2D3]/rat/day; OVX + 7.5 ng 1,25(OH)2D3/rat/day + 15 ng 1,24,25(OH)3D3/rat/day; OVX + 7.5 ng 1,25(OH)2D3/rat/day + 75 ng 24,25(OH)2D3/rat/day. The vitamin D metabolites were fed orally starting 4 weeks after surgery. Urine and blood samples were collected 12 and 16 weeks postovariectomy, respectively. Sixteen weeks after surgery, all rats were sacrificed, and the first lumbar vertebrae were processed undecalcified for histomorphometric analysis. Ovariectomy induced a highly significant reduction (P < 0.001) of cancellous bone mass in the secondary spongiosa of the lumbar vertebral body. The bone loss in OVX rats was accompanied by a distinct elevation of all histomorphometric parameters of bone formation and resorption. 1,25(OH)2D3 and both vitamin D metabolite combinations significantly raised serum calcium levels and prevented the bone loss by inhibiting the increased bone resorption in OVX rats. In the applied dosage, 1,24,25(OH)3D3 and 24,25(OH)2D3 alone were ineffective in preserving the cancellous bone of the lumbar vertebra in OVX rats. We conclude that the oral prophylactic application of low doses of active vitamin D metabolites can effectively prevent the osteopenia induced by ovariectomy in the axial skeleton of the rat.