Changes in Periosteal and Endocortical Width Across the Menopausal Transition

项目摘要 对女性来说，绝经过渡(MT)是骨骼强度下降的关键时期，在此期间，大约 一生中有一半的人会失去骨密度(BMD)。虽然在临床上和研究中，BMD是 骨质疏松症的主要指标，它不能揭示骨结构的变化，需要充分了解 与年龄相关的体力衰退。这项提议旨在更好地阐明造成亏损的结构性变化 通过检查皮质内扩张(骨丢失)与骨膜的相对变化来评估MT期间的强度 膨胀(骨量增加)。这两个特征定义了骨骼强度，但它们各自的方式 MT期间的结构指数变化在很大程度上是未被探索的。我们的中心假设是骨骼强度 与窄骨骼的女性相比，宽骨骼的女性下降得更早、更快。这 假设是由我们的流行病学和身体研究中有希望的初步数据发现指导的 提示在骨骼的初始阶段，可能会建立个性化的强度下降轨迹 女性的损失，以及外部骨大小(例如，骨宽度、总横截面积)可以识别女性 在骨折高危人群中。我们将首先验证新的骨强度指标并测试其生物学基础 我们在身体组织中的假设(目标1)。我们对身体组织的研究表明，大脑皮质内 宽骨与窄骨的孔隙度相比，表明不同的强度衰减轨迹可能来自于 基于BMU的重塑。因为这只能用组织切片进行精确的研究，我们将 将身体研究(目标1)与活体人体研究(目标2，3)结合起来，为 从纵向数据得出的观测结果。我们将使用现有的两个纵向数据来测试我们的中心假设 数据库--在40-60岁的女性中，从20岁前过渡到20年来获得的图像数据 到绝经后。我们将在MT期间将基线骨骼特征与结构和强度变化联系起来 承重、易骨折的骨(股骨近端)和非承重、非易骨折的骨 (掌骨)，以评估其诊断髋部力量变化的临床价值。具体来说，我们建议 1)测试基准外骨大小与MT过程中强度指数变化之间的关系 参加密歇根州骨骼健康和代谢研究(MBHMS)的白人女性，然后2)测试 白人女性在MT期间失去更多与更少骨强度之间的区别因素 MBHM预测整个MT期间白人和黑人女性MT相关力量的下降 《全国妇女健康研究(天鹅)》20年。这项研究解决了一个显著的差距 科学知识阻碍了我们优化骨折预防策略的能力。如果我们的假设证明 正确的，基线外骨大小可以作为一个额外的参数来识别女性最有可能 在MT期间，骨强度迅速下降，谁可能从早期干预中受益。成功完成 我们的目标将提供基本的新信息，关于具体的结构和材料参数 可以最好地为临床决策提供信息。

Project Summary For women, the menopausal transition (MT) is a critical period of decline in bone strength, during which about half the lifetime loss in bone mineral density (BMD) occurs. While clinically, and in research, BMD is the primary indicator for osteoporosis, it does not reveal the changes in bone structure needed to fully understand age-related loss in strength. This proposal seeks to better elucidate the structural changes that underlie loss in strength during the MT by examining relative changes in endocortical expansion (bone loss) versus periosteal expansion (bone gain). These two features define bone strength, but the manner in which each of these structural indices changes during the MT is largely unexplored. Our central hypothesis is that bone strength declines earlier and more rapidly in women with wide bones compared to women with narrow bones. This hypothesis is guided by promising preliminary data findings in our epidemiologic and cadaver studies which suggest that individualized trajectories of strength-decline may be established during the initial phase of bone loss for women, and that external bone size (e.g., bone width, total cross-sectional area) may identify women in a high fracture-risk group. We will first validate new bone strength indices and test for the biological basis of our hypothesis in cadaveric tissue (Aim 1). Our work in cadaveric tissue has shown greater intra-cortical porosity in wide compared to narrow bones, suggesting different strength-decline trajectories may arise from BMU-based remodeling. Because this can only be studied precisely using histological sections, we will combine cadaveric studies (Aim 1) with living human studies (Aims 2,3) to provide a biological basis for observations derived from longitudinal data. We will test our central hypothesis using two existing longitudinal databases with image-data acquired over 20 years among 40-60 year-old women as they transition from pre- to post-menopause. We will relate baseline bone traits to structural and strength changes during the MT in a weight-bearing, fracture prone bone (proximal femur) and a nonweight-bearing, non-fracture prone bone (metacarpal) to assess its clinical value for diagnosing strength changes at the hip. Specifically, we propose to 1) test for associations between baseline external bone size and changes in strength indices during the MT for white women in the Michigan Bone Health and Metabolism Study (MBHMS) and then 2) test whether the factors that differentiate between white women who lose more vs. less bone strength during the MT in the MBHMS are predictive of MT-related strength declines in white and black women followed across the MT over 20 years in the Study of Women’s Health Across the Nation (SWAN). This study addresses a significant gap in scientific knowledge that impedes our ability to optimize fracture prevention strategies. If our hypotheses prove correct, baseline external bone size may be used as an additional parameter to identify women most likely to lose bone strength rapidly during the MT and who might benefit from early intervention. Successful completion of our Aims will provide fundamental new information about what specific structural and material parameters can best inform clinical decisions.