Takeshita N, Yoshino T, Mutoh S, Yamaguchi I
Tsukuba Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.
Life Sci. 1994;55(4):291-9. doi: 10.1016/0024-3205(94)00731-4.
To explore the pathogenesis of diabetes associated osteopenia, we characterized the osteopenia in streptozotocin (STZ)-diabetic rats pharmacologically and biochemically. The femur metaphyseal bone mineral density measured by single photon absorptiometry decreased time-dependently in the STZ rats compared with that in control, and the difference reached statistical significance from 2 weeks after treatment with STZ. Closely similar bone loss was obtained in ovariectomized (Ovx) and vitamin D deficient(D(-)) rats. Daily oral treatment with a bone resorption inhibitor, FR78844 (a bisphosphonate compound, 100 mg/kg), for 4 weeks significantly attenuated the osteopenia in the STZ and Ovx rats, but not in the D(-) rats, while 1 alpha-hydroxyvitamin D3 (1 alpha-(OH)D3) significantly attenuated the osteopenia in the STZ and D(-) rats in a dose of 0.1 microgram/kg/day, and that in the Ovx rats in 1 microgram/kg/day. The latter dose of 1 alpha-(OH)D3 significantly increased the metaphyseal bone mineral density of the femur in normal rats. Serum levels of 1 alpha, 25-dihydroxyvitamin D (1 alpha, 25-(OH)2D), the most active metabolite of vitamin D, hardly changed in the Ovx rats compared with that in control, but decreased to 24 and 76% that of control in the STZ and D(-) rats, respectively. Serum PTH levels in the STZ, Ovx and D(-) rats were comparable with those in controls, but serum calcitonin levels were reduced to 60 and 66% of control in the STZ and Ovx rats, respectively. Serum osteocalcin levels also decreased in the STZ rats compared to control. It is thus speculated that the predominance of bone resorption over bone formation and the reduction of 1 alpha, 25-(OH)2D are involved in the pathogenesis of diabetes associated osteopenia.
为探讨糖尿病相关性骨质减少的发病机制，我们从药理学和生物化学角度对链脲佐菌素（STZ）诱导的糖尿病大鼠的骨质减少进行了特征分析。与对照组相比，通过单光子吸收法测得的STZ大鼠股骨干骺端骨矿物质密度随时间呈下降趋势，且自STZ治疗2周后差异具有统计学意义。去卵巢（Ovx）大鼠和维生素D缺乏（D(-)）大鼠也出现了极为相似的骨质流失情况。每日口服骨吸收抑制剂FR78844（一种双膦酸盐化合物，100 mg/kg），持续治疗4周，可显著减轻STZ大鼠和Ovx大鼠的骨质减少，但对D(-)大鼠无效；而1α-羟基维生素D3（1α-(OH)D3）以0.1μg/kg/天的剂量可显著减轻STZ大鼠和D(-)大鼠的骨质减少，以1μg/kg/天的剂量可减轻Ovx大鼠的骨质减少。后一剂量的1α-(OH)D3可显著增加正常大鼠股骨干骺端的骨矿物质密度。维生素D最具活性的代谢产物1α,25-二羟基维生素D（1α,25-(OH)2D）的血清水平，与对照组相比，Ovx大鼠几乎未发生变化，但在STZ大鼠和D(-)大鼠中分别降至对照组的24%和76%。STZ大鼠、Ovx大鼠和D(-)大鼠的血清甲状旁腺激素（PTH）水平与对照组相当，但STZ大鼠和Ovx大鼠的血清降钙素水平分别降至对照组的60%和66%。与对照组相比，STZ大鼠的血清骨钙素水平也有所降低。因此推测，骨吸收超过骨形成的优势以及1α,25-(OH)2D的减少参与了糖尿病相关性骨质减少的发病机制。
