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

最近的几项研究表明，维生素D不仅能影响骨骼，还能影响肌肉，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不清楚。在这项研究中，我们研究了α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（BMD）的影响。7月龄Wistar雌性大鼠卵巢切除（OVX）或假手术后，口服阿法骨化醇（0.1 μg/kg/天）或其载体4周。末次给药次日，在全麻下切开跟腱远端，连接力传感器，暴露坐骨神经，电刺激20个周期。测量每个刺激周期小腿肌肉的最大收缩张力来评估肌肉力量。每个刺激周期的肌肉疲劳被评估为每个周期强度与初始收缩强度的百分比。肌肉力量和疲劳度然后用体重归一化。测量肌力和疲劳后，取右股骨，用双能x线骨密度仪测量股骨远端三分之一处的骨密度。与各自的对照组相比，假手术组和OVX组的阿法骨化醇给药显著增加了最大肌肉力量。然而，阿法骨化醇给药对这些组的肌肉疲劳没有显著影响。阿法骨化醇治疗的OVX组BMD明显高于载体治疗的OVX组。我们得出结论，阿法骨化醇增加肌肉力量，但不影响肌肉疲劳的大鼠模型。维生素D在预防骨折方面的有效性可能部分是由于它对肌肉力量的影响，以及它对骨骼代谢的已知影响。

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.