Bisphosphonate modulates morphological and mechanical properties in distraction osteogenesis through inhibition of bone resorption.
Bisphosphonate modulates morphological and mechanical properties in distraction osteogenesis through inhibition of bone resorption.
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DOI：
10.1016/j.bone.2006.03.010
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发表时间：
2006-09
期刊：
影响因子：
4.1
通讯作者：
Mitsuhiko Takahashi;K. Yukata;Y. Matsui;A. Abbaspour;S. Takata;N. Yasui
中科院分区：
文献类型：
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作者：
Mitsuhiko Takahashi;K. Yukata;Y. Matsui;A. Abbaspour;S. Takata;N. Yasui
尽管牵张成骨在临床上得到了广泛的接受，并且在这种方法中骨形成受到了很大的关注，但对再生骨中的激活骨吸收的认识却很少。本研究的目的是证明同时激活的骨吸收和激活的骨形成，并探讨双磷酸盐在牵张成骨中的作用和效果。54只幼兔左侧胫骨延迟1周后，以0.7 mm/d的速度延长3周。通过放射骨密度、骨组织形态计量学和三点弯曲试验对新生骨进行定量研究。动物分别给予赋形剂或含氮双膦(N-BP)YM529/ONO59200.4g/kg/w或0.004 mg/kg/w，共6周。赋形剂组新生骨表现为放射学特征的带状结构，含有与硬化区相邻的骨质疏松区。0.4 mg/kg/w组的再生骨在整个过程中未见骨质疏松区，最终形成均匀的放射性密度。与赋形剂组相比，该组骨质疏松带对应的骨体积增加5.6倍。该组延长的骨强度是赋形剂组的3.3倍，相当于对侧胫骨。0.004 mg/kg/w组与赋形剂组相比没有显著差异，尽管矿化前沿的放射学增强以及骨吸收有所延迟。这些结果表明，在再生骨中，不仅骨形成而且骨吸收都高度活跃，这意味着骨转换很高。足够的N-BP通过抑制高度活化的骨吸收，最终提高力学性能，对再生骨的形态特性产生显著的调节作用。
Despite the general clinical acceptance of distraction osteogenesis and much attention to bone formation in this method, little is recognized about activated bone resorption in the regenerated bone. 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.