Evaluation of Osteoporotisis Drugs by Histological, Biochemical Approach in Experimental Osteoporosis Model

实验性骨质疏松模型中通过组织学、生化方法评价骨质疏松药物

• 批准号: 16591470
• 负责人: ITOI Eiji
• 金额: $ 0.9万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591470/
• 关键词: vitamin D; osteoporosis; muscle strength; muscle fatigue; ビタミンK

Several recent studies have demonstrated that vitamin D affects not only bone but also muscle to prevent falls and osteoporotic fractures. However, these effects on muscle and the mechanisms of fall-prevention are still unclear. In this study, we investigated the effects of alfacalcidol (1α(OH)D3) on muscle strength, muscle fatigue, and bone mineral density (BMD) in normal and ovariectomized rats.Following ovariectomy (OVX) or sham operation in 7-month-old female Wistar rats, alfacalcidol (0.1 μg/kg/day) or its vehicle was administered orally for 4 weeks. On the day after the final administration, the distal end of the Achilles' tendon was cut and attached to a force transducer under general anesthesia, and the sciatic nerve was exposed and electrically stimulated for 20 cycles. The maximum contraction tension of the calf muscles for each stimulation cycle was measured to evaluate muscle strength. Muscle fatigue at each stimulation cycle was evaluated as the percentage strength at each cycle to the initial contraction strength. Muscle strength and fatigue were then normalized using the body weight. After the measurement of muscle strength and fatigue, the right femur was harvested to measure the BMD at the distal third of the femur by dual energy x-ray absorptiometry.Alfacalcidol administration significantly increased the maximum muscle strength in the sham-operated and the OVX groups compared to their respective control groups. However, alfacalcidol administration did not significantly affect muscle fatigue in these groups. The BMD in the alfacalcidol-treated OVX group was significantly higher than that in the vehicle-treated OVX group.We conclude that alfacalcidol increases muscle strength, but does not affect muscle fatigue in the rat model. The effectiveness of vitamin D in preventing fractures may be partly due to its effect on muscle strength in addition to its known effect on bone metabolism.

最近的几项研究表明，维生素D不仅影响骨骼，还影响肌肉，以防止跌倒和骨质疏松性骨折。然而，这些对肌肉的影响和预防跌倒的机制仍然不清楚。本研究观察了阿法骨化醇(1α(OH)D3)对正常和去卵巢大鼠肌肉力量、肌肉疲劳和骨密度的影响。在7月龄雌性Wistar大鼠去卵巢或假手术后，口服阿法骨化醇(0.1μg/kg/d)或其载体，连续4周。末次给药后第二天，在全麻下切断跟腱远端，连接到力传感器上，暴露坐骨神经，电刺激20个循环。测量每个刺激周期小腿肌肉的最大收缩张力，以评估肌肉力量。每个刺激周期的肌肉疲劳以每个周期的力量占初始收缩强度的百分比来评估。然后用体重将肌肉力量和疲劳归一化。在测量肌肉力量和疲劳后，取右侧股骨，用双能X线骨密度仪测量股骨远端1/3处的骨密度，阿法骨化醇给药组大鼠的最大肌力明显高于各自的对照组。然而，阿法骨化醇给药对这些组的肌肉疲劳没有显著影响。阿法骨化醇治疗OVX组大鼠骨密度显著高于赋形剂治疗OVX组，提示阿法骨化醇可增加大鼠模型肌肉力量，但不影响肌肉疲劳。维生素D预防骨折的有效性可能部分是因为它除了对骨骼代谢有已知的影响外，还对肌肉力量有影响。