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Modulation of Bone Remodeling during Distraction Osteogenesis

牵张成骨过程中骨重塑的调节

基本信息

批准号：
16390441
负责人：
YASUI Natsuo
金额：
$ 9.28万
依托单位：
The University of Tokushima
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
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

项目摘要

The purpose of this study was to demonstrate the simultaneously activated bone resorption with activated bone formation and to investigate the role and efficacy of bisphosphonate in distraction osteogenesis. Left tibiae of 54 immature rabbits were lengthened for 3 weeks at a rate of 0.7 mm/day after a 1-week lag. Regenerated bone was quantitatively investigated by radiographic bone density, bone histomorphometry, and three-point-bending testing. Animals received either vehicle or nitrogen-containing bisphosphonate (N-BP), YM529/ONO5920 at doses of 0.4 mg/kg/w or 0.004 mg/kg/w for 6 weeks. Regenerated bone of the vehicle group showed a radiologically characteristic zone structure containing the osteopenic zones adjacent to the sclerotic zones. The regenerated bone of the 0.4-mg/kg/w group showed no osteopenic zones during the course and eventually became homogeneously radiodense. The bone volume corresponding to the osteopenic zone of this group was 5.6-fold greater compared with that of the vehicle group. The lengthened bone strength of this group was 3.3-fold greater in ultimate force than that of the vehicle group and equivalent to the contralateral tibia. The 0.004-mg/kg/w group had no substantial differences compared with the vehicle group, despite radiological enhancement of the mineralized front as well as somewhat delayed bone resorption. These results demonstrate that not only bone formation but also bone resorption is highly activated in the regenerated bone, implying high bone turnover. Sufficient N-BP caused a notable modulation in morphological properties of the regenerated bone through inhibition of highly activated bone resorption and eventually increased mechanical properties.

本研究的目的是证明同时激活骨吸收与激活骨形成，并探讨双膦酸盐在牵张成骨中的作用和疗效。54只幼兔左胫骨延迟1周后，以0.7mm/d的速度延长3周。通过放射学骨密度、骨组织形态计量学和三点弯曲试验对再生骨进行定量研究。动物以0.4 mg/kg/w或0.004 mg/kg/w的剂量接受媒介物或含氮双膦酸盐（N-BP），YM 529/ONO 5920，持续6周。溶剂组的再生骨显示出放射学特征性区域结构，其包含与骨质疏松区相邻的骨质减少区。0.4 mg/kg/w组的再生骨在整个过程中未显示骨质减少区，并最终变得均匀的放射密度。与溶剂组相比，该组骨质减少区对应的骨体积大5.6倍。该组的延长骨强度在极限力方面比载体组大3.3倍，并且与对侧胫骨相当。0.004 mg/kg/w组与溶剂组相比无实质性差异，尽管矿化前沿放射学增强以及骨吸收略微延迟。这些结果表明，在再生骨中，不仅骨形成而且骨吸收高度活化，这意味着高骨转换。足够的N-BP通过抑制高度活化的骨吸收并最终增加机械性能，引起再生骨的形态学特性的显著调节。