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Is the plate to rod transition in trabecular bone loss a real phenomenon or a spurious result of a misused metric?

小梁骨丢失中的板到杆的转变是真实现象还是误用指标的虚假结果？

基本信息

批准号：
BB/P006167/1
负责人：
Richard Bomphrey
金额：
$ 27.95万
依托单位：
Royal Veterinary College
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FP006167%2F1
关键词：
plate rod transition trabecular bone

项目摘要

A latticework of bony trabeculae stiffens the internal spaces of many bones. Trabeculae transmit forces between joint surfaces and bone shafts and maintain the integrity of vertebrae. Bone loss is a normal physiological response to reduced mechanical load, occurring during bed rest, in sedentary lifestyles, and during the weightlessness of spaceflight. Bone loss is also a normal, undesirable, part of ageing which occurs particularly rapidly in women after menopause. Reduced bone mass is strongly associated with increased fracture risk. Peak bone mass is obtained in humans in early adulthood. Strategies to increase peak bone mass and to slow its physiological loss are of great interest to ensure healthy ageing.In addition to bone mass (bone volume fraction, BV/TV), bone architecture is thought to play a crucial role in trabecular bone's force transmission and fracture resistance. Bone architecture is defined by standard measurements such as trabecular thickness (Tb.Th), spacing (Tb.Sp), interconnectedness (Conn.D), anisotropy (DA) and rod-plate geometry (structure model index, SMI). The bulk behaviour of trabecular bone in physiological loading is almost entirely determined by BV/TV: this is intuitive because the more bone matrix there is per unit volume, the greater the overall volume can resist applied load. Once a higher failure load has been reached, however, the behaviour of trabecular elements dominates collapse of the overall structure. Each trabecula might fail by buckling, shear or crumpling. Bone biologists believe that plate-like trabeculae resist higher loads than rod-like trabeculae and that plate-like trabeculae convert to rod-like trabeculae during bone loss, creating a 'double-whammy': reduced bulk resistance to load due to decreased BV/TV and reduced resistance to trabecular element failure due to rod-like geometry.Whether a plate-to-rod transition actually occurs in bone loss is now in serious doubt, because the paradigm is based on flawed SMI measurements. I recently showed that variation in SMI during bone loss is dominated by increasing amounts of concave portions of the bone surface, which the SMI theory assumes are not there or have a negligible contribution. There is a high correlation between SMI and BV/TV even when the underlying architecture has not changed. SMI is a fundamentally broken measurement that does not do what bone bioscientists use it for. Over 850 papers have cited SMI and a common interpretation when seeing BV/TV and SMI results together is that bone loss is associated with a plate-to-rod transition, however, this is merely an artefact of SMI's design that obscures any true relationship. Statements linking bone loss and plate-rod transition have been repeated often enough to have become an accepted dogma in the bone field.This project aims to overturn the dogma there is a plate to rod transition in bone loss using 3D X-ray microtomography (XMT) image data sets archived from previous experiments. To measure rods and plates independent of BV/TV, the PDRA will validate a new method, ellipsoid factor (EF), that defines rods and plates by the shape of the biggest ellipsoid that fits within each bony region. Rods can fit long, javelin-shaped ellipsoids, while plates can fit flat, discus-shaped ellipsoids. The PDRA will use image data collected on RVC's XMT instrument, images from my project partner Phil Salmon at Bruker microCT, and from other collaborators worldwide, and aim to increase our current pool of ~150 images from 3 studies to ~1000 images from ~20 studies. Having identified rods and plates in bone samples, the PDRA will correlate rods and plates with mechanical behaviour using finite elements analysis in the physiological load range for bulk behaviour and overload range for trabecular element failure behaviour. The primary benefit of the work is improved understanding of true geometric and mechanical changes in bone loss, along with the new EF method and free software.

骨小梁的网格结构使许多骨的内部空间变硬。骨小梁在关节面和骨干之间传递力并保持椎骨的完整性。骨丢失是对机械负荷减少的正常生理反应，发生在卧床休息、久坐不动的生活方式和航天失重期间。骨质流失也是一种正常的，不受欢迎的，衰老的一部分，在绝经后的妇女中发生得特别快。骨量减少与骨折风险增加密切相关。人类在成年早期达到峰值骨量。增加峰值骨量和减缓其生理损失的策略对于确保健康的老龄化具有极大的意义。除了骨量（骨体积分数，BV/TV）之外，骨结构被认为在松质骨的力传递和抗骨折性中起着至关重要的作用。骨结构由标准测量值定义，如骨小梁厚度（Tb.Th）、间距（Tb.Sp）、互连性（Conn.D）、各向异性（DA）和棒-板几何形状（结构模型指数，SMI）。生理负荷下松质骨的整体行为几乎完全由BV/TV决定：这是直观的，因为每单位体积的骨基质越多，总体积可以抵抗施加的负荷越大。然而，一旦达到更高的破坏载荷，小梁元件的行为主导整个结构的坍塌。每个骨小梁可能因屈曲、剪切或起皱而失效。骨生物学家认为，板状骨小梁比杆状骨小梁抵抗更高的负荷，并且在骨丢失期间板状骨小梁转化为杆状骨小梁，从而产生“双重打击”：由于BV/TV降低而导致的对载荷的整体阻力降低，以及由于杆状几何形状而导致的对小梁元件失效的阻力降低。板-棒过渡是否实际上发生在骨丢失中现在受到严重怀疑，因为这个范例是基于有缺陷的SMI测量。我最近表明，在骨丢失过程中SMI的变化主要是由骨表面凹陷部分的数量增加所决定的，SMI理论假设不存在或贡献可以忽略不计。SMI和BV/TV之间存在高度相关性，即使底层架构没有改变。SMI是一种根本上不完整的测量方法，它不能完成骨生物科学家使用它的目的。超过850篇论文引用了SMI，当同时看到BV/TV和SMI结果时，一种常见的解释是骨丢失与板-棒过渡相关，然而，这仅仅是SMI设计的一个假象，掩盖了任何真实的关系。骨丢失和板-棒过渡之间的联系已经被反复提及，已经成为骨领域公认的教条。本项目旨在利用先前实验中存档的3D X射线显微断层扫描（XMT）图像数据集，推翻骨丢失中存在板-棒过渡的教条。为了测量不受BV/TV影响的棒和板，PDRA将确认一种新方法，椭圆体因子（EF），该方法通过适合每个骨区域的最大椭圆体的形状定义棒和板。杆可以适合长的、标枪形的椭圆，而板可以适合平的、铁饼形的椭圆。PDRA将使用在RVC的XMT仪器上收集的图像数据，来自布鲁克microCT的项目合作伙伴Phil Salmon以及全球其他合作者的图像，旨在将我们目前的3项研究的约150张图像库增加到约20项研究的约1000张图像。在确定骨样本中的棒和板后，PDRA将在生理载荷范围内使用有限元分析将棒和板与力学行为相关联，以确定体积行为和小梁元件失效行为的过载范围。这项工作的主要好处是提高了对骨丢失的真实几何和力学变化的理解，沿着新的EF方法和免费软件。