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.

骨小梁的格子晶格使许多骨骼的内部空间变硬。小梁在关节表面和骨轴之间传递力，并保持椎骨的完整性。骨质流失是对减少机械负荷的正常生理反应，在床休息期间，久坐的生活方式以及太空飞行的失重期间发生。骨质流失也是正常的，不受欢迎的衰老一部分，在更年期后女性中特别迅速发生。骨骼质量减少与骨折风险增加密切相关。在成年初期，人类获得了峰值骨质量。增加峰值骨质和减慢生理损失的策略是确保健康老化的极大兴趣。除了骨骼质量（骨体积分数，BV/TV）外，骨骼建筑被认为在小梁骨的力传播和抗断裂性方面起着至关重要的作用。骨结构由标准测量值（例如小梁厚度（TB.TH），间距（TB.SP），互连度（CONN.D），各向异性（DA）和杆板几何形状（结构模型指数，SMI））定义。小梁骨在生理负荷中的批量行为几乎完全由BV/TV确定：这是直观的，因为每单位体积的骨基质越多，总体体积越大可以抵抗施加的载荷。但是，一旦达到了更高的故障负荷，小梁元素的行为主导了整体结构的崩溃。每个小梁可能会因屈曲，剪切或折断而失败。骨骼生物学家认为，类似板的小梁比杆状小梁抗能抵抗更高的负荷，而板状小梁则转变为骨质流失过程中的杆状小梁，造成了“双重打击”：由于BV/TV的降低而导致的压力减少，因此由于板状的损失而导致的板状损失降低，因此降低了载荷的损失，实际上是杆骨的损失。怀疑，因为范式基于缺陷的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的凹入部分增加，而SMI理论假定不存在或具有可忽略的贡献。即使基础架构没有改变，SMI和BV/TV之间也存在很高的相关性。 SMI是一种从根本上破裂的测量，无法执行骨生物科学家使用的方法。当看到BV/TV和SMI结果在一起时，超过850篇论文引用了SMI和一种共同的解释，这是骨质流失与板到统计的过渡有关，但是，这仅仅是SMI设计的伪像，它掩盖了任何真实关系。将骨质流失和板杆转变联系起来的陈述经常被重复，以成为骨骼场中公认的教条。此项目旨在推翻教条，使用3D X射线微观学（XMT）图像数据集在先前的实验中存档。为了测量与BV/TV无关的杆和板，PDRA将验证一种新方法椭圆形因子（EF），该方法通过适合每个骨质区域的最大椭球的形状来定义杆和板。杆可以容纳长长的标枪形椭圆形，而板则可以安装平坦的铁饼形椭圆形。 PDRA将使用RVC的XMT仪器收集的图像数据，来自Bruker Microct的项目合作伙伴Phil Salmon的图像，以及来自全球其他合作者的图像数据，并旨在将目前的150张图像库从3个研究增加到〜20个研究的〜1000张图像。在识别骨样品中的杆和板后，PDRA将使用有限元元素分析在生理负载范围内的散装行为和过载范围内的有限元分析将杆和板与机械行为相关联，以实现小梁元素失败行为。这项工作的主要优势是对骨质流失的真正几何变化以及新的EF方法和免费软件的真正几何变化和机械变化有了改善的理解。