Osteopenia in genetically diabetic DB/DB mice and effects of 1alpha-hydroxyvitamin D3 on the osteopenia. Basic Research Group.
Osteopenia in genetically diabetic DB/DB mice and effects of 1alpha-hydroxyvitamin D3 on the osteopenia. Basic Research Group.
复制标题
遗传性糖尿病 DB/DB 小鼠的骨质减少以及 1α-羟基维生素 D3 对骨质减少的影响。
作者：
N. Takeshita;S. Mutoh;I. Yamaguchi
为探讨非胰岛素依赖型糖尿病相关性骨量减少的发病机制，我们采用单光子吸收法检测了同品系遗传性糖尿病（db/db）小鼠和非糖尿病（+/+）小鼠股骨干骺端骨密度的增龄性变化，并对骨量减少进行了形态学和生化表征。在5 - 16周龄的+/+小鼠中，骨密度随年龄增加，但在8周龄的db/db小鼠中达到平台期，并且在12周龄后观察到两组之间的显著差异。8周龄后，db/db小鼠的股骨灰重（A）和干重（D）以及A/D比值显著低于+/+小鼠。血清钙和甲状旁腺激素（PTH）显着升高后，8周龄和12周龄，分别观察。与+/+小鼠相比，db/db小鼠的血清1 α，25-二羟维生素D水平显著降低。从8周龄开始，每天口服1 α-羟基维生素D3（1 α-（OH）D3）4周，可显著减轻db/db小鼠的骨丢失。这些结果表明，可能由维生素D活性不足和高PTH水平引起的骨矿化受损与db/db小鼠的骨质减少有关。1 α-（OH）D3对骨丢失具有有益作用。
To explore the pathogenesis of non-insulin-dependent diabetes mellitus associated osteopenia, we examined age-related changes of the femur metaphyseal bone mineral density in genetically diabetic (db/db) mice and non-diabetic (+/+) mice of the same strain using single photon absorptiometry and characterized the osteopenia pharmacologically and biochemically. Bone mineral density increased with age in the +/+ mice from 5 to 16 weeks of age, but reached a plateau in the db/db mice at 8 weeks of age, and significant differences between the two groups were observed after 12 weeks of age. Ash weight (A) and dry weight (D) of the femur and A/D ratio were significant lower in the db/db mice than in the +/+ mice after 8 weeks of age. Significant elevations of serum calcium and parathyroid hormone (PTH) were observed after 8 weeks and 12 weeks of age, respectively. Serum 1alpha,25-dihydroxyvitamin D levels were significantly decreased in the db/db mice compared to the +/+ mice. Daily oral treatment with 1alpha-hydroxyvitamin D3 (1alpha-(OH)D3) for 4 weeks starting from 8 weeks of age significantly attenuated the bone loss in the db/db mice. These results suggest that an impaired bone mineralization probably by insufficient vitamin D activity and high PTH levels are involved in the osteopenia in the db/db mice. 1alpha-(OH)D3 exerted beneficial effects on the bone loss.