Kobayashi M, Hara K, Akiyama Y
Pharmacological Evaluation Section, Department of Applied Drug Research, Eisai Co., Ltd., Bunkyo, Tokyo 112-8088, Japan.
Bone. 2004 Nov;35(5):1136-43. doi: 10.1016/j.bone.2004.05.012.
In this study, we examined changes in bone parameters and bone strength in rats fed low-Mg diets (experiment 1) and the effects of vitamin K2 (MK-4, experiment 3) and alendronate (ALN, experiment 2) in this model. In experiment 1, 5-week-old male Wistar rats were fed three low-Mg diets (Mg 9, 6, 3 mg/100 g diet) for 4 weeks. Although the cortical bone mineral content (CtBMC) and cortical thickness (CtTh) of the femoral diaphysis in all low-Mg-diet groups were the same as or greater than those in the intact group (Mg: 90 mg/100 g diet), the maximum load and elastic modulus were significantly reduced in the 3-mg-Mg group. In experiment 2, 4-week-old Wistar rats were fed a 6-mg-Mg diet for 8 weeks, and the effect of ALN (2, 20, and 200 microg/kg twice a week) was evaluated. The administration of ALN at 200 microg/kg increased the cortical bone mineral content (CtBMC), CtTh, and maximum load, but had no effect on the elastic modulus, as compared with the low-Mg-control group. In experiment 3, the effect of MK-4 was evaluated under the same conditions as in experiment 2. The administration of MK-4 had no effect on CtBMC, CtTh, or bone components of the femoral diaphysis. However, MK-4 inhibited the decreases in maximum load and elastic modulus due to the low-Mg diet. Since there is no other experimental model in which there is a decrease in bone mechanical properties without a decrease in bone mineral content, the low-Mg diet model is considered to be an excellent model for examining bone quality. Our results from this model suggest that MK-4 and ALN affect bone mechanical properties by different mechanisms.
在本研究中,我们检测了喂食低镁饮食的大鼠的骨参数和骨强度变化(实验1),以及维生素K2(甲萘醌-4,实验3)和阿仑膦酸盐(ALN,实验2)在此模型中的作用。在实验1中,5周龄雄性Wistar大鼠喂食三种低镁饮食(镁含量分别为9、6、3mg/100g饮食),持续4周。尽管所有低镁饮食组的股骨干皮质骨矿物质含量(CtBMC)和皮质厚度(CtTh)与完整组(镁含量:90mg/100g饮食)相同或更高,但3mg镁组的最大负荷和弹性模量显著降低。在实验2中,4周龄Wistar大鼠喂食6mg镁饮食8周,并评估ALN(2、20和200μg/kg,每周两次)的作用。与低镁对照组相比,200μg/kg的ALN给药增加了皮质骨矿物质含量(CtBMC)、CtTh和最大负荷,但对弹性模量没有影响。在实验3中,在与实验2相同的条件下评估甲萘醌-4的作用。甲萘醌-4给药对股骨干的CtBMC、CtTh或骨成分没有影响。然而,甲萘醌-4抑制了由于低镁饮食导致的最大负荷和弹性模量的降低。由于没有其他骨矿物质含量不降低而骨力学性能降低的实验模型,低镁饮食模型被认为是研究骨质量的优秀模型。我们从该模型得到的结果表明,甲萘醌-4和ALN通过不同机制影响骨力学性能。