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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.

骨小梁的网格使许多骨头的内部空间变硬。小梁在关节表面和骨干之间传递力并维持椎骨的完整性。骨质流失是对机械负荷减少的正常生理反应，发生在卧床休息、久坐的生活方式和太空飞行失重期间。骨质流失也是衰老过程中正常但不受欢迎的一部分，这种情况在绝经后的女性中发生得尤其快。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老龄化具有重要意义。除了骨量（骨体积分数，BV/TV）之外，骨结构被认为在小梁骨的力传递和抗骨折性中发挥着至关重要的作用。骨结构通过标准测量来定义，例如小梁厚度 (Tb.Th)、间距 (Tb.Sp)、互连性 (Conn.D)、各向异性 (DA) 和杆板几何形状（结构模型指数，SMI）。骨小梁在生理负荷中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就越大。然而，一旦达到更高的失效载荷，小梁元件的行为就会主导整个结构的倒塌。每个小梁都可能因弯曲、剪切或压皱而失效。骨生物学家认为，板状小梁比杆状小梁能承受更高的载荷，并且板状小梁在骨质流失过程中会转化为杆状小梁，从而产生“双重打击”：由于 BV/TV 降低而降低了整体对载荷的抵抗力，并且由于杆状几何形状而降低了对小梁元件失效的抵抗力。在骨质流失中是否真正发生板状到杆状的转变现在是一个严重的问题怀疑，因为该范例是基于有缺陷的 SMI 测量。我最近表明，骨质流失期间 SMI 的变化主要是由骨表面凹入部分数量的增加决定的，而 SMI 理论认为凹入部分不存在或贡献可以忽略不计。即使底层架构没有改变，SMI 和 BV/TV 之间也存在高度相关性。 SMI 是一种从根本上被破坏的测量方法，不能达到骨生物科学家所使用的目的。超过 850 篇论文引用了 SMI，当同时看到 BV/TV 和 SMI 结果时，常见的解释是骨质流失与板到杆的过渡有关，然而，这只是 SMI 设计的一个假象，掩盖了任何真正的关系。将骨质流失和板棒转变联系起来的说法已经被重复多次，足以成为骨领域公认的教条。该项目旨在使用从以前的实验中存档的 3D X 射线显微断层扫描 (XMT) 图像数据集来推翻骨质流失中存在板棒转变的教条。为了独立于 BV/TV 测量杆和板，PDRA 将验证一种新方法，即椭球因子 (EF)，该方法通过适合每个骨区域的最大椭球的形状来定义杆和板。杆可以适合长的标枪形状的椭球体，而板可以适合平坦的铁饼形状的椭球体。 PDRA 将使用在 RVC 的 XMT 仪器上收集的图像数据、来自我的项目合作伙伴 Bruker microCT 的 Phil Salmon 以及来自世界各地其他合作者的图像，并旨在将我们目前来自 3 项研究的约 150 张图像增加到来自约 20 项研究的约 1000 张图像。在识别出骨样本中的杆和板后，PDRA 将使用有限元分析将杆和板与机械行为关联起来，在生理负荷范围内进行体积行为，在过载范围内进行小梁元件失效行为。这项工作的主要好处是提高了对骨质流失的真实几何和机械变化的理解，以及新的 EF 方法和免费软件。