Shiraishi A, Higashi S, Masaki T, Saito M, Ito M, Ikeda S, Nakamura T
Product Research Laboratory, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
Calcif Tissue Int. 2002 Jul;71(1):69-79. doi: 10.1007/s00223-001-2090-y. Epub 2002 Jun 20.
We conducted this study to evaluate the characteristic effects of alfacalcidol (ALF) and menatetrenone (VK) in preventing bone loss using an ovariectomized rat model of osteoporosis. Bilateral ovariectomy (OVX) or sham operation was performed on 10-month-old female Wistar rats. OVX caused a significant decrease in the bone mass and the mechanical strength of the lumbar vertebra as well as the femur 6 months after surgery. VK treatment (30 mg/kg, food intake) required a 6-month period to prevent the bone loss induced by estrogen deficiency, whereas ALF (0.1 or 0.2 mg/kg, p.o.) increased the bone mass and the mechanical strength of the lumbar vertebra as well as the femur in a 3-month treatment period, far above the level in the sham-operated rats. Neither ALF or VK caused hypercalcemia, despite administration for as long as 6 months. By doing a micro-CT analysis of the vertebral trabecular microstructure, it was revealed that ALF treatment increased the interconnections and the plate-like structures and that VK significantly increased the trabecular number. It was also indicated that the increase in spinal strength by ALF treatment was closely associated with improvement of the microstructure, but not VK. The results of histomorphometric analysis showed that ALF caused a significant suppression of bone resorption yet maintained formation in the endocortical perimeter, and also stimulated bone formation in the periosteal perimeter, thereby causing an increase in cortical area. No marked effect of VK on histomorphometric parameters was observed, whereas VK as well as ALF maintained the material strength at femoral midshaft of the normal level, suggesting that VK affected bone quality and thereby prevented the decrease in mechanical strength of femur caused by OVX. In conclusion, it was demonstrated that the two drugs, ALF and VK, differed markedly in their potency and mechanisms for improving bone strength. These results have important implications in understanding the characteristic actions of vitamin K and active vitamin D on bone metabolism.
我们进行这项研究，以使用去卵巢大鼠骨质疏松模型评估阿法骨化醇（ALF）和维生素K2（VK）在预防骨质流失方面的特征性作用。对10月龄雌性Wistar大鼠进行双侧卵巢切除术（OVX）或假手术。术后6个月，OVX导致腰椎和股骨的骨量及机械强度显著降低。VK治疗（30 mg/kg，经食物摄入）需要6个月时间来预防雌激素缺乏引起的骨质流失，而ALF（0.1或0.2 mg/kg，口服）在3个月的治疗期内增加了腰椎和股骨的骨量及机械强度，远远高于假手术大鼠的水平。尽管给药长达6个月，ALF和VK均未引起高钙血症。通过对椎骨小梁微观结构进行显微CT分析发现，ALF治疗增加了骨小梁的连接性和板状结构，而VK显著增加了骨小梁数量。还表明，ALF治疗引起的脊柱强度增加与微观结构的改善密切相关，而VK则不然。组织形态计量学分析结果显示，ALF显著抑制骨吸收，但在内皮质周边维持骨形成，并且还刺激骨膜周边的骨形成，从而导致皮质面积增加。未观察到VK对组织形态计量学参数有明显影响，而VK和ALF均将股骨干中部的材料强度维持在正常水平，这表明VK影响骨质量，从而预防了OVX引起的股骨机械强度下降。总之，证明了ALF和VK这两种药物在提高骨强度的效力和机制方面存在显著差异。这些结果对于理解维生素K和活性维生素D对骨代谢的特征性作用具有重要意义。
