ROLE OF VITAMIN-D METABOLITES IN THE PREVENTION OF THE OSTEOPENIA INDUCED BY OVARIECTOMY IN THE AXIAL AND APPENDICULAR SKELETON OF THE RAT
ROLE OF VITAMIN-D METABOLITES IN THE PREVENTION OF THE OSTEOPENIA INDUCED BY OVARIECTOMY IN THE AXIAL AND APPENDICULAR SKELETON OF THE RAT
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DOI：
10.1007/bf02023080
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发表时间：
1990-12-01
期刊：
影响因子：
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通讯作者：
RAMBECK, WA
中科院分区：
文献类型：
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作者：
ERBEN, RG;KOHN, B;RAMBECK, WA
40 只 Fischer-344 大鼠（10 周龄，体重 130 g）进行双侧卵巢切除 (OVX) 或假手术 (SHAM)。 将大鼠分配至以下组：SHAM组；去卵巢； OVX + 15 ng 1-α,25-二羟基维生素 D3 [1,25(OH)2D3]/大鼠/天； OVX + 30 ng 1-α,24R,25-三羟基维生素 D3 [1,24,25(OH)3D3]/大鼠/天； OVX + 15 ng 1,25(OH)2D3/大鼠/天 + 30 ng 1,24,25(OH)3D3/大鼠/天。 术后 4 周开始口服维生素 D 代谢物。 在实验过程中的几个时间点采集尿液和血液样本。 术后21周处死所有大鼠，对近端胫骨和第一腰椎进行未脱钙处理，用于静态骨组织形态测定。卵巢切除导致椎体松质骨面积减少40%，胫骨松质骨面积减少69%。 与假手术动物的值相比，OVX 大鼠的骨丢失与骨形成和吸收的生化和组织形态学指数的适度增加有关。 通过抑制骨吸收，用 1,25(OH)2D3、1,24,25(OH)3D3 及其代谢物组合治疗 OVX 大鼠，可预防卵巢切除引起的腰椎骨质减少，并部分预防胫骨干骺端的松质骨骨质减少。 然而，单独接受1,25(OH)2D3或与1,24,25(OH)3D3联合治疗的OVX大鼠表现出高钙血症、高磷血症、高钙尿症和骨矿化受损。 另一方面，单独用 1,24,25(OH)3D3 治疗 OVX 大鼠，仅轻微增加血清钙水平，并且不会损害骨矿化。 此外，1,24,25(OH)3D3 与 1,25(OH)2D3 的包含部分拮抗了 1,25(OH)2D3 对骨矿化的不利影响。这些数据表明 1,24,25(OH)3D3 对骨代谢的作用可能不同于 1,25(OH)2D3，并且 1,25(OH)2D3，特别是， 1,24,25(OH)3D3 可能是预防绝经后骨质疏松症的潜在有效药物。
Forty Fischer-344 rats (10 weeks old, 130 g BW) were either bilaterally ovariectomized (OVX) or sham-operated (SHAM). The rats were allocated to the following groups: SHAM; OVX; OVX + 15 ng 1-alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3]/rat/d; OVX + 30 ng 1-alpha,24R,25-trihydroxyvitamin D3 [1,24,25(OH)3D3]/rat/d; OVX + 15 ng 1,25(OH)2D3/rat/d + 30 ng 1,24,25(OH)3D3/rat/d. The vitamin D metabolites were fed orally starting 4 weeks after surgery. Urine and blood samples were taken at several time points during the experiment. Twenty-one weeks after surgery all rats were sacrificed, and the proximal tibiae and the first lumbar vertebrae were processed undecalcified for static bone histomorphometry.Ovariectomy induced a 40 % reduction in vertebral cancellous bone area, and a 69 % reduction in tibial cancellous bone area. This bone loss in OVX rats was associated with moderately increased biochemical and histomorphometric indices of bone formation and resorption as compared to values in sham-operated animals. Through inhibition of bone resorption, treatment of OVX rats with 1,25(OH)2D3, 1,24,25(OH)3D3, and the metabolite combination prevented the ovariectomy-induced osteopenia in the lumbar vertebra, and partially prevented cancellous bone osteopenia in the tibial metaphysis. However, OVX rats receiving 1,25(OH)2D3 alone or in combination with 1,24,25(OH)3D3 exhibited hypercalcemia, hyperphosphatemia, hypercalciuria, and impaired bone mineralization. Treatment of OVX rats with 1,24,25(OH)3D3 alone, on the other hand, only slightly increased serum calcium levels and did not impair bone mineralization. Furthermore, the inclusion of 1,24,25(OH)3D3 with 1,25(OH)2D3 partially antagonized the untoward effects of 1,25(OH)2D3 on bone mineralization.These data suggest that the actions of 1,24,25(OH)3D3 on bone metabolism might differ from that of 1,25(OH)2D3, and that 1,25(OH)2D3 and, particularly, 1,24,25(OH)3D3 may be potentially effective agents for the prophylaxis of postmenopausal osteoporosis.