Progression and etiology of cortical porosity in diabetic bone disease

糖尿病骨病皮质疏松的进展和病因

基本信息

项目摘要

SUMMARY Diabetic bone disease, with its elevated risk for fragility fracture, is increasingly recognized as a distinct entity that cannot be assessed sufficiently with standard methods used for osteoporosis. Severe deficits in cortical bone structure, specifically increased cortical porosity, are associated with fracture prevalence in T2D. Cortical porosity has deleterious effects on bone strength, and is critical in fracture initiation and propagation. Despite the biomechanical importance of cortical porosity, the origins and temporal evolution of pathological cortical porosity in T2D are unknown. To develop treatments specifically targeted to the prevention or reversal of pathological cortical porosity and associated bone fragility in T2D, we must understand the mechanisms driving development of these large cortical pores. Today, these mechanisms are unknown though many have been posited, including endocortical `trabecularization' and expansion of the Haversian network. We hypothesize that determining the content and spatial distribution of cortical pore space will reveal biological systems influencing pore expansion. Marrow within pores near the endosteal border may indicate endocortical `trabecularization', or infiltration of the marrow cavity into the cortical envelope. Alternatively, vessels within pores distributed throughout the cortex may indicate pore formation via expansion of the vascular network. The identification of biological systems associated with pore expansion will elucidate appropriate cellular targets for drug development. The overall goal of this proposed study is to understand the longitudinal evolution of human diabetic bone disease and to investigate the underlying biological processes that drive increased cortical porosity in the setting of T2D. We propose the first longitudinal study of pore progression in T2D patients, which will be performed using a novel combined high-resolution peripheral quantitative computed tomography (HR-pQCT) and contrast enhanced magnetic resonance (MR) imaging approach, with the following aims: I: Determine if increased porosity in T2D is associated with altered marrow distribution and composition, II: Determine if increased porosity in T2D is associated with altered vessel distribution and vascular health, and III: Determine if T2D status or marrow or vessel metrics predict longitudinal increase in porosity and decrease in strength. To address aims I and II, we will perform multimodal imaging in a cross-sectional cohort of T2D patients and matched control subjects. To address aim III, we will follow these subjects in a 2-year longitudinal study. This work will establish whether cortical pore content can serve as a predictor of future cortical degradation, and begin to elucidate biological drivers and possible drug targets for the prevention or reversal of T2D-associated pathological porosity and bone fragility, laying the groundwork for future therapeutic studies. With the number of devastating diabetic fragility fractures increasing, these studies have the potential for immense clinical impact.
总结 糖尿病性骨疾病,其脆性骨折的风险增加,越来越多地被认为是一个独特的实体 这不能用用于骨质疏松症的标准方法充分评估。严重的皮质功能缺陷 骨结构,特别是增加的皮质孔隙度,与2型糖尿病骨折的发生率相关。皮质 多孔性对骨强度具有有害影响,并且在骨折开始和扩展中是关键的。尽管 皮质孔隙度的生物力学重要性,病理性皮质的起源和时间演变, T2 D中的孔隙度未知。开发专门针对预防或逆转 在T2 D中,病理性皮质多孔性和相关的骨脆性,我们必须了解驱动T2 D的机制。 这些大的皮质孔的发育。今天,这些机制是未知的,虽然许多已经 假设,包括皮质内“小梁化”和哈弗氏网络的扩张。我们假设 确定皮层孔隙的含量和空间分布将揭示生物系统 影响孔隙膨胀。骨髓在骨内膜边缘附近的孔内可能表明皮质内 “小梁化”,或骨髓腔浸润到皮质包膜中。或者, 分布在整个皮层的孔可以指示通过血管网扩张的孔形成。的 与孔扩张相关的生物系统的鉴定将阐明合适的细胞靶, 药物开发这项研究的总体目标是了解人类的纵向进化 糖尿病性骨疾病,并研究驱动皮质骨增加的潜在生物学过程, 在T2 D环境下的孔隙度。我们提出了T2 D患者毛孔进展的第一个纵向研究, 这将使用一种新的组合高分辨率外周定量计算机断层扫描进行, (HR-pQCT)和对比增强磁共振(MR)成像方法,目的如下: 确定T2 D中孔隙率增加是否与骨髓分布和组成改变相关,II: 确定T2 D中孔隙率增加是否与血管分布和血管健康改变相关,III: 确定T2 D状态或骨髓或血管指标是否可预测孔隙率的纵向增加和 实力为了实现目标I和II,我们将在T2 D的横断面队列中进行多模式成像 患者和匹配的对照组。为了实现目标三,我们将对这些主题进行为期两年的纵向跟踪, study.这项工作将确定皮质孔含量是否可以作为未来皮质功能的预测因子。 降解,并开始阐明生物驱动程序和可能的药物靶点,用于预防或逆转 T2 D相关的病理性多孔性和骨脆性,为未来的治疗研究奠定基础。 随着破坏性糖尿病脆性骨折数量的增加,这些研究有可能 巨大的临床影响。

项目成果

期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Cortical bone vessel identification and quantification on contrast-enhanced MR images.
对比增强 MR 图像上的皮质骨血管识别和量化。
  • DOI:
    10.21037/qims.2019.05.23
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    2.8
  • 作者:
    Wu,Po-Hung;Gibbons,Matthew;Foreman,SarahC;Carballido-Gamio,Julio;Han,Misung;Krug,Roland;Liu,Jing;Link,ThomasM;Kazakia,GalateiaJ
  • 通讯作者:
    Kazakia,GalateiaJ
Soft tissue variations influence HR-pQCT density measurements in a spatially dependent manner.
软组织变化以空间相关的方式影响 HR-pQCT 密度测量。
  • DOI:
    10.1016/j.bone.2020.115505
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    4.1
  • 作者:
    Wu,Po-Hung;Gupta,Tanvi;Chang,Hanling;Petrenko,Dimitry;Schafer,Anne;Kazakia,Galateia
  • 通讯作者:
    Kazakia,Galateia
Microstructural abnormalities are evident by histology but not HR-pQCT at the periosteal cortex of the human tibia under CVD and T2D conditions.
在 CVD 和 T2D 条件下,人类胫骨骨膜皮质的微观结构异常通过组织学检查是明显的,但 HR-pQCT 则不明显。
  • DOI:
    10.1016/j.medntd.2021.100062
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Garita,Barbara;Maligro,Jenna;Sadoughi,Saghi;Wu,PoHung;Liebenberg,Ellen;Horvai,Andrew;Link,ThomasM;Kazakia,GalateiaJ
  • 通讯作者:
    Kazakia,GalateiaJ
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GALATEIA J KAZAKIA其他文献

GALATEIA J KAZAKIA的其他文献

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{{ truncateString('GALATEIA J KAZAKIA', 18)}}的其他基金

Determining the Biological Mechanisms of Pathological Cortical Porosity
确定病理性皮质孔隙的生物学机制
  • 批准号:
    10251896
  • 财政年份:
    2020
  • 资助金额:
    $ 47.7万
  • 项目类别:
Determining the Biological Mechanisms of Pathological Cortical Porosity
确定病理性皮质孔隙的生物学机制
  • 批准号:
    10474404
  • 财政年份:
    2020
  • 资助金额:
    $ 47.7万
  • 项目类别:
Imaging Core
成像核心
  • 批准号:
    10460471
  • 财政年份:
    2019
  • 资助金额:
    $ 47.7万
  • 项目类别:
Imaging Core
成像核心
  • 批准号:
    10215390
  • 财政年份:
    2019
  • 资助金额:
    $ 47.7万
  • 项目类别:
Imaging Core
成像核心
  • 批准号:
    10642794
  • 财政年份:
    2019
  • 资助金额:
    $ 47.7万
  • 项目类别:
Bone quality and marrow adiposity in subjects with HIV
HIV 感染者的骨质量和骨髓肥胖
  • 批准号:
    10067367
  • 财政年份:
    2016
  • 资助金额:
    $ 47.7万
  • 项目类别:
Bone quality and marrow adiposity in subjects with HIV
HIV 感染者的骨质量和骨髓肥胖
  • 批准号:
    9271800
  • 财政年份:
    2016
  • 资助金额:
    $ 47.7万
  • 项目类别:
Visualizing Cortical Pore Space Constituents
可视化皮质孔隙空间成分
  • 批准号:
    8585475
  • 财政年份:
    2013
  • 资助金额:
    $ 47.7万
  • 项目类别:
Visualizing Cortical Pore Space Constituents
可视化皮质孔隙空间成分
  • 批准号:
    8884378
  • 财政年份:
    2013
  • 资助金额:
    $ 47.7万
  • 项目类别:
Visualizing Cortical Pore Space Constituents
可视化皮质孔隙空间成分
  • 批准号:
    8702086
  • 财政年份:
    2013
  • 资助金额:
    $ 47.7万
  • 项目类别:

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以额叶功能为中心的汽车驾驶能力评价方法的建立及其在事故预测中的应用
  • 批准号:
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    25330237
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    2013
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    $ 47.7万
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  • 批准号:
    23591741
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    2011
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