Long term fracture risk and change in peripheral bone in the oldest old men: The MrOS study

最年长男性的长期骨折风险和周围骨变化：MrOS 研究

• 批准号: 10304929
• 负责人: MARY L BOUXSEIN
• 金额: $ 259.18万
• 依托单位: CALIFORNIA PACIFIC MED CTR RES INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10304929
• 关键词: Abdomen; Abdominal Pain; Address; Adult; Age; Aged, 80 and over; Aging; Award; Biological; Bone Density; Bone structure; Clinical; Communities; Current Procedural Terminology Codes; Data; Deterioration; Diagnosis; Dual-Energy X-Ray Absorptiometry; Elderly; Finite Element Analysis; Fracture; Health care facility; Hip Fractures; Hip region structure; Image; Individual; Knowledge; Long-Term Care; Measures; Medical; Morbidity - disease rate; Nature; Osteoporosis; Pathway interactions; Pattern; Pelvic Pain; Pelvis; Peripheral; Phase; Prevention; Prevention strategy; Process; Proteomics; Public Health; Risk; Scanning; Skeleton; Spinal Fractures; Structure; Sum; Systems Biology; Vertebral column; X-Ray Computed Tomography; age related; bone; bone imaging; bone loss; bone strength; cohort; cortical bone; cost; design; fall risk; falls; follow-up; fracture risk; frailty; high risk; high risk men; human old age (65+); human very old age (85+); improved; insight; men; metabolomics; mortality; multiple omics; novel; older men; optimal treatments; reduced muscle mass; skeletal; spine bone structure; substantia spongiosa; treatment strategy; Abdomen; Abdominal Pain; Address; Adult; Age; Aged, 80 and over; Aging; Award; Biological; Bone Density; Bone structure; Clinical; Communities; Current Procedural Terminology Codes; Data; Deterioration; Diagnosis; Dual-Energy X-Ray Absorptiometry; Elderly; Finite Element Analysis; Fracture; Health care facility; Hip Fractures; Hip region structure; Image; Individual; Knowledge; Long-Term Care; Measures; Medical; Morbidity - disease rate; Nature; Osteoporosis; Pathway interactions; Pattern; Pelvic Pain; Pelvis; Peripheral; Phase; Prevention; Prevention strategy; Process; Proteomics; Public Health; Risk; Scanning; Skeleton; Spinal Fractures; Structure; Sum; Systems Biology; Vertebral column; X-Ray Computed Tomography; age related; bone; bone imaging; bone loss; bone strength; cohort; cortical bone; cost; design; fall risk; falls; follow-up; fracture risk; frailty; high risk; high risk men; human old age (65+); human very old age (85+); improved; insight; men; metabolomics; mortality; multiple omics; novel; older men; optimal treatments; reduced muscle mass; skeletal; spine bone structure; substantia spongiosa; treatment strategy

In this competitive revision application, we aim to address three critical aims to understand the determinants and impact of fractures and peripheral bone loss in the ongoing MrOS study. In our first aim, we will characterize circumstances of fractures in the oldest old. We will leverage the longitudinal follow-up of MrOS men to carefully determine the circumstances of incident fractures in the oldest old, community-dwelling men. We hypothesize that the types and circumstances of fractures will differ between active non-frail men compared to inactive frail men. In our second aim, we will improve understanding of age-related loss of peripheral bone. Given the large impact of fractures in the peripheral skeleton, we will analyze recently obtained 5-year follow-up HR-pQCT measures of peripheral bone microarchitecture to gain insight into skeletal fragility in the peripheral skeleton. Specifically, we will a) establish the rate and character of peripheral bone loss in older men. We hypothesize that we will identify distinct patterns of cortical vs. trabecular bone deterioration; with cortical bone loss contributing more to declines in bone strength by µFEA than trabecular bone loss, b) determine whether low muscle mass and low activity are related to peripheral bone loss. We hypothesize that they will be robust, independent predictors of bone loss, and c) utilize systems biology approaches to identify novel pathways related to loss of peripheral bone density, structure and strength. We hypothesize that state-of-the-art multi- omic approaches, leveraging comprehensive proteomic and metabolomic measures, will identify biological pathways associated with increased peripheral bone loss and structural declines in older men. In our third aim, we will determine the utility of hip and spine CT to predict fracture risk in older men. With FDA approval and recent awarding of a CPT code, use of abdominal-pelvic CT images acquired for older medical reasons holds promise as a new clinical paradigm to expand the identification of those at high risk of fractures. We will compute new estimates of bone strength in 3695 men with existing MrOS CT scans to address key knowledge gaps for how to best utilize CT-FEA for fracture prediction. Specifically, we will a) determine whether bone strength from CT-FEA at the hip and spine predicts short- and long-term with fracture risk. We hypothesize that the combination of femoral and vertebral strength predicts incident fracture better than either alone, and that femoral and vertebral strength predict both short- and long-term fracture risk as well as DXA- BMD, and b) simulate multiple fall-loading directions to quantify hip strength. We posit that femoral strength in the “weakest” loading direction better predicts hip fracture than the “standard” sideways fall loading direction. MrOS is uniquely suited to address several key clinical and mechanistic knowledge gaps regarding skeletal fragility in older men. The study's comprehensive bone imaging, its long follow-up and the very old age of the cohort provide unparalleled opportunities to generate novel information.

在此竞争性修订应用中，我们旨在解决三个关键目标，以了解决定者 在正在进行的MROS研究中，裂缝和周围骨质流失的影响。 在我们的第一个目标中，我们将描述最古老的骨折情况。我们将利用 MROS男子的纵向随访，以仔细确定最古老的事件裂缝的情况 古老的社区居民。我们假设裂缝的类型和情况将有所不同 与非活动的脆弱男人相比，活跃的非狂欢男子。 在我们的第二个目标中，我们将提高人们对年龄相关的外围骨损失的理解。给出大 裂缝在外围骨骼中的影响，我们将分析最近获得的5年随访HR-PQCT 外围骨微结构的度量，以深入了解外围骨骼中的骨骼脆弱性。 具体而言，我们将a）确定老年男性外围骨质流失的速度和特征。我们假设 我们将确定皮质与小梁骨质流失的不同模式 比小梁骨质流失更多地促进骨强度下降的骨骼强度，b）确定是否低 肌肉质量和低活性与外围骨质流失有关。我们假设它们会很健壮， 骨质流失的独立预测指标，c）利用系统生物学方法来识别新途径 与外周骨密度，结构和强度的丧失有关。我们假设最先进的多 掌握综合蛋白质组学和代谢组学措施的OMIC方法将确定生物学 与老年男性的外围骨质流失和结构下降有关的途径。 在我们的第三个目标中，我们将确定髋关节和脊柱CT的效用，以预测老年男性的骨折风险。与FDA 批准和最近授予了CPT代码，使用用于较老的医疗的腹 - 螺旋体CT图像 理由将有望作为一种新的临床范式扩大裂缝高风险的临床范围。 我们将计算3695名现有MROS CT扫描的男性的骨骼强度的新估计值以解决密钥 如何最好地利用CT-FEA进行断裂预测的知识差距。具体来说，我们将a）确定 CT-FEA的骨骼强度是否在短期和长期骨折风险下进行。我们 假设股骨和椎力强度预测的结合比任何一个都更好 单独使用，股骨和椎骨强度可以预测短期和长期骨折的风险以及DXA- BMD和B）模拟多个跌倒方向以量化髋关节强度。我们肯定股骨力量 与“标准”的侧面载荷方向相比，“最弱”的加载方向更好地预测髋部骨折。 MROS独特地适合解决有关骨骼的几个关键临床和机械知识差距 老年男子的脆弱性。该研究的全面骨骼成像，长期的随访和非常年老的 队列提供了无与伦比的机会来生成新的信息。