Department of Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany.
Injury. 2013 Jul;44(7):923-9. doi: 10.1016/j.injury.2013.02.029. Epub 2013 Mar 20.
Angiogenesis is pivotal for bone metabolism and bone defect healing. Yet the role of vascularization in osteoporosis and osteoporotic bone repair mechanisms is unclear. Here we investigated effects of osteoporotic phenotype on vascularization during bone defect healing in a rodent osteotomy model using volumetric computed tomography (VCT), dynamic contrast-enhanced VCT (DCE-VCT), dynamic contrast-enhanced MRI (DCE-MRI) and histology. In 16 rats, 8 with physiological bone status (SHAM) and 8 with osteoporotic bone status induced by ovariectomy (OVX) in combination with a vitamin D- and low calcium diet, wedge-shaped defects were created at the left distal femur and stabilized internally by T-shaped miniplate. MRI and VCT were performed in all animals 6 weeks after this procedure. By VCT, relative bone density in the defect was evaluated. Using DCE-VCT and DCE-MRI, parameters associated with regional blood volume were calculated in the bone defect, vicinity of the defect, surrounding muscles and bone marrow: Amplitude A and exchange rate constant Kep (DCE-MRI, respectively) as well as peak enhancement PE and area under the curve AUC (DCE-VCT, respectively). In animals of osteoporotic phenotype, bone density within the osseous defect was significantly reduced as compared to SHAM rats. Vascularization parameters determined by DCE-MRI and DCE-VCT in the defect were significantly elevated compared to the adjacent tissues for both SHAM and OVX groups. However, comparing SHAM and OVX rats, no statistically different values were found by DCE-MRI and DCE-VCT concerning any determined vascularization parameter within the bone defect. Furthermore, parameters of vascularization were increased for OVX as compared to SHAM rats within the bone marrow although significant difference was only found for A. In a rat osteotomy model we showed that at the reparative healing stage, osteoporotic phenotype did influence osteogenic but not angiogenic response within bone defect as imaged by DCE-MRI and DCE-VCT. This study provides insight into the relationship between angiogenesis and osteogenesis during osteoporosis-related compromised bone healing.
血管生成对于骨代谢和骨缺损愈合至关重要。然而，血管生成在骨质疏松症和骨质疏松性骨修复机制中的作用尚不清楚。在这里，我们使用容积 CT（VCT）、动态对比增强 CT（DCE-VCT）、动态对比增强 MRI（DCE-MRI）和组织学研究了骨质疏松表型对骨缺损愈合过程中血管生成的影响，该研究使用了啮齿动物截骨模型。在 16 只大鼠中，8 只具有生理骨状态（SHAM），8 只具有骨质疏松骨状态，通过卵巢切除术（OVX）与维生素 D 和低钙饮食联合诱导，在左侧股骨远端创建楔形缺损，并通过 T 形微型板内部稳定。所有动物在该手术后 6 周进行 MRI 和 VCT 检查。通过 VCT 评估缺损内的相对骨密度。使用 DCE-VCT 和 DCE-MRI，计算骨缺损、缺损附近、周围肌肉和骨髓中的与区域血容量相关的参数：幅度 A 和交换率常数 Kep（DCE-MRI 分别）以及峰值增强 PE 和曲线下面积 AUC（DCE-VCT，分别）。在骨质疏松表型的动物中，与 SHAM 大鼠相比，骨缺损内的骨密度明显降低。与 SHAM 和 OVX 两组的相邻组织相比，DCE-MRI 和 DCE-VCT 确定的骨缺损内的血管生成参数显著升高。然而，比较 SHAM 和 OVX 大鼠，DCE-MRI 和 DCE-VCT 确定的任何骨缺损内的血管生成参数均无统计学差异。此外，与 SHAM 大鼠相比，OVX 大鼠骨髓内的血管生成参数增加，尽管仅 A 存在显著差异。在大鼠截骨模型中，我们表明在修复愈合阶段，骨质疏松表型确实影响 DCE-MRI 和 DCE-VCT 成像的骨缺损内的成骨而不是血管生成反应。这项研究提供了在与骨质疏松症相关的受损骨愈合过程中血管生成和成骨之间关系的见解。
