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

在加拿大，骨折是一个严重的健康问题。每年都有许多妇女和男子受到影响，造成严重损害，生活质量下降，甚至死亡。加拿大卫生保健系统的经济负担很大，预计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。这些位置的特征在于高比例的松质骨，这种组织可以被描述为板和杆的3D网络，称为小梁。骨小梁的大小、分布和方向--称为结构--在我们的一生中不断变化，因为我们的身体通过一个称为重塑的过程来适应我们当前的负荷需求。例如，随着年龄的增长，活动减少或代谢变化可能导致骨丢失，这意味着骨小梁更少更小。骨矿物质密度（BMD）测试是诊断这种骨质流失的常用方法;不幸的是，BMD只表明有多少骨存在，而不是组织本身的质量。因此，在那些经历和不经历骨折的人之间，BMD值有很大的重叠。需要更多关于骨组织的信息来改善骨折风险的预测。重塑过程以小步骤发生，其中现有组织被吸收并产生新组织。随着时间的推移，每一步的积累都会产生骨小梁，这些骨小梁是由称为骨结构单位（BSU）的小区域拼凑而成的，也称为半骨单位或骨小梁包，它们被高度矿化的骨水泥层彼此隔开。由此产生的拼接可以比作一堵不规则形状的砖墙，其中每块砖（BSU）被一层砂浆（水泥线）彼此隔开。在我们实验室和其他地方的先前工作表明，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和失效行为，增加某人的骨折风险;然而，它们仍然没有得到充分的研究。这项研究有三个目标。第一个是确定BSU几何形状的变化与人体骨骼中不同位置的小梁结构变化之间的联系。第二个目标是通过创建理想化BSU的扩展有限元法（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几何形状变化的机械后果。最后，第三个目标是确定大鼠中是否发生类似的变化，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几何形状。成功完成这三个目标将有利于加拿大人的健康和安全，提高我们对骨小梁BSU在年龄相关性骨折中的作用的理解，并可以改善骨折风险评估。

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.