A comparison of alfacalcidol and menatetrenone for the treatment of bone loss in an ovariectomized rat model of osteoporosis
A comparison of alfacalcidol and menatetrenone for the treatment of bone loss in an ovariectomized rat model of osteoporosis
复制标题
DOI：
10.1007/s00223-001-2090-y
复制
发表时间：
2002-07-01
影响因子：
4.2
通讯作者：
Nakamura, T
中科院分区：
文献类型：
--
作者：
Shiraishi, A;Higashi, S;Nakamura, T
我们进行了这项研究，以评估阿法骨化醇（ALF）和menatetrenone（VK）在预防骨质疏松症的卵巢切除大鼠模型的骨丢失的特征效果。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和机械强度显著下降。VK治疗（30 mg/kg，食物摄入）需要6个月的时间来防止由雌激素缺乏引起的骨丢失，而ALF（0.1或0.2 μ g/kg，p.o.）在3个月的治疗期内增加腰椎和股骨的骨量和机械强度，远高于假手术大鼠的水平。无论是ALF或VK引起高钙血症，尽管管理长达6个月。通过对椎体小梁显微结构进行显微CT分析，发现ALF治疗增加了互连和板状结构，VK显著增加了小梁数量。ALF治疗后脊柱强度的增加与微结构的改善密切相关，而与VK无关。组织形态计量学分析的结果表明，ALF引起了显着抑制骨吸收，但保持形成在皮质内周边，也刺激骨形成在骨膜周边，从而导致皮质面积增加。VK对组织形态计量学参数无明显影响，而VK和ALF维持股骨中段的材料强度在正常水平，表明VK影响骨质量，从而防止OVX引起的股骨机械强度降低。总之，研究表明，ALF和VK这两种药物在改善骨强度的效力和机制方面存在显著差异。这些结果对理解维生素K和活性维生素D对骨代谢的特征作用具有重要意义。
We conducted this study to evaluate the characteristic effects of alfacalcidol (ALF) and menatetrenone (VK) in preventing bone loss using a 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 mug/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.