Quantifying the nature and consequences of morphological changes in trabecular bone structural units (BSU)

在加拿大，与年龄相关的骨折是一个严重的健康问题。许多女性和男性每年都会受到影响，导致严重的损伤，生活质量下降，甚至死亡。加拿大医疗保健系统的经济负担很大，预计会随着人口老龄化而增加。前臂、髋部和椎骨是大多数与年龄相关的骨折发生的骨骼部位。这些部位的特点是高比例的松质骨，这种组织可以描述为称为小梁的板和杆的3D网络。骨小梁的大小、分布和方向在我们的一生中都会发生变化，因为我们的身体通过一个称为重塑的过程来适应我们目前的负荷需求。例如，随着年龄的增长，活动减少或代谢变化会导致骨丢失，这意味着骨小梁越来越少。骨密度(BMD)测试是诊断这种骨丢失的常见方法；不幸的是，BMD只指示存在多少骨，而不是组织本身的质量。因此，骨折患者和未骨折患者的骨密度值有很大重叠。需要更多关于骨组织的信息来提高对骨折风险的预测。重建过程以很小的步骤进行，其中现有组织被吸收，新组织被创造出来。随着时间的推移，每一步的积累都会导致骨小梁的形成，这些小梁是由称为骨结构单元(BSU)的小区域拼凑而成的，也称为半骨节或小梁包，由高度矿化的水泥线层相互分隔。由此产生的拼接可以比作一堵不规则形状的砖(BSU)的墙，每一块砖(BSU)都被一层砂浆(水泥线)隔开。我们实验室和其他地方之前的工作表明，BSU随着年龄的增长和小梁结构的恶化而变小。这些变化预计会降低骨骼的机械性能和失效行为，增加某人骨折的风险；然而，它们仍未得到充分研究。这项拟议的研究有三个目标。第一个是确定BSU几何结构的变化与人类骨骼不同位置小梁结构的变化之间的联系。第二个目标是通过创建理想化的BSU的扩展有限元方法(Xfem)模型来模拟不同形状和尺寸分布如何加速或减缓裂纹扩展，从而确定BSU几何形状变化的力学后果。最后，第三个目标是确定在大鼠身上是否发生了类似的变化，以便将来可以进行对照实验研究，以发现各种因素如何影响BSU的几何形状。成功地完成这三个目标将有利于加拿大人的健康和安全，因为它提高了我们对骨小梁BSU在年龄相关性骨折中所起作用的理解，并可能改善骨折风险评估。

Age-related fractures are a serious health concern in Canada. Many women and men are affected every year, resulting in significant impairment, reduced quality of life, and even death. The economic burden on the Canadian health care system is large and is expected to increase as the population ages. The forearm, hip, and vertebrae are the skeletal sites where most age-related fractures occur. These locations are characterized by a high-proportion of cancellous bone, a tissue which can be described as a 3D network of plates and rods called trabeculae. The size, distribution, and orientation of the trabeculae -referred to as the architecture- changes throughout our lifetimes as our bodies adapt to meet our current loading needs through a process called remodeling. For example, decreased activity or metabolic changes with age can result in bone loss, which means fewer and smaller trabeculae. Bone mineral density (BMD) tests are a common way to diagnose this bone loss; unfortunately, BMD only indicates how much bone is present and not the quality of the tissue itself. As a result, there is a large overlap in BMD values between those that do and do not experience a fracture. More information about bone tissue is needed to improve predictions of fracture risk. The remodeling process occurs in small steps where existing tissue is resorbed and new tissue is created. Over time, the accumulation of each step results in trabeculae that are a patchwork of little regions called bone structure units (BSU) -also known as hemiosteons or trabecular packets- separated from each other by highly mineralized layers of cement line. The resulting patchwork can be compared to a wall of irregularly shaped bricks where each brick (BSU) is separated from each other by a layer of mortar (cement line). Previous work, in our lab and elsewhere, has shown that BSU get smaller with age and deteriorating trabecular architecture. These changes are expected to decrease the mechanical and failure behaviour of the bone, increasing someone's fracture risk; however, they remain under-studied. The proposed research has three goals. The first is to determine the connection between the changes in BSU geometry and the changes in the trabecular architecture at different locations in the human skeleton. The second goal is to identify the mechanical consequences of the changes in BSU geometry by creating extended finite element method (XFEM) models of idealized BSU to simulate how different shape and size distributions hasten or slow crack propagation. Finally, the third goal is to determine whether similar changes occur in rats so that controlled experimental studies can be performed in the future to discover how various factors affect BSU geometry. Successfully completing these three goals will benefit the health and safety of Canadians by improving our understanding of the role that trabecular BSU play in age-related fractures and could improve fracture-risk assessment.