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

摘要 骨折和由此导致的发病率、死亡率和费用是老年男性的一个巨大且不断增长的负担。骨折发生率在65岁以后呈指数增长，髋部骨折的平均年龄为80岁。骨密度、结构和强度的长期下降对晚年的骨折风险有很大影响，在此期间骨骼变化加速。 男性骨质疏松性骨折研究(MROS)是一项对老年男性骨质疏松性骨折危险因素进行的前瞻性研究。这项研究继续跟踪那些最初在2000-2年间注册的男性。MROS是年龄最大的男性的最佳表型队列-现在是9岁和10岁-骨折是维持独立性的主要威胁。20多年前，我们开始获得系列DXA检测并完成临床表型。 基线时，进行髋部和脊柱CT扫描(N=3695)，以评估骨结构和强度。同样，2014-2006年在大量男性(N=1831)中进行了HR-pQCT(XtremeCTII)扫描。因此，MROS仍然是关于男性肌肉骨骼老化的数据和发现的独特来源，并且特别适合于解决有关老年男性骨骼脆性的几个关键的临床和机械知识空白。这项研究的全面骨骼成像、长期的随访和队列的高龄提供了无与伦比的机会，可以产生设计有效方法减轻老年男性骨折负担所需的新信息。 该项目的总体目标是为研究的组织提供连续性，继续为MROS项目提供基础设施，允许继续跟踪参与者，并支持收集有限的研究测量数据。 该项目的具体目标是支持正在进行的MROS基础设施。这些措施包括：1)继续对MRO参与者进行骨折、跌倒、活动受限和死亡的随访；2)在活跃的MRO参与者子集中收集重复的HR-pQCT扫描；以及3)维持研究交流的科学组织；出版物和辅助审查；以及公共数据发布基础设施。 这些目标将提供实现未来科学目标所需的关键框架，例如表征高龄老年人骨折的情况；通过HR-pQCT量化周围骨微结构的变化并确定这种变化的决定因素；以及确定基于髋部和脊柱CT的CT-FEA措施在预测老年男性骨折风险方面的效用。

ABSTRACT Fractures and resulting morbidity, mortality and costs are a large and growing burden among older men. The fracture rate increases exponentially after age 65, and the average age of hip fracture is >80 yrs. Fracture risk in later life is strongly influenced by long term declines in bone density, structure and strength, and during this period skeletal change accelerates. The Osteoporotic Fractures in Men Study (MrOS) is an ongoing, prospective study of risk factors for osteoporotic fractures in older men. The study continues to follows men who were initially enrolled in 2000-2. MrOS is best phenotyped cohort of the oldest men – now in the 9th and 10th decades of life – when fractures are a major threat to maintaining independence. More than 20 years ago, we began to obtain serial DXA measures and complete clinical phenotyping. At baseline, hip and spine CT scans (N=3695) were obtained to assess bone structure and strength. Similarly, HR-pQCT (XtremeCTII) scans were obtained in a large number of men (N=1831) in 2014-6. Thus, MrOS remains the unique source of data and discoveries about musculoskeletal aging in men, and 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 needed to design effective approaches to reduce the burden of fractures in older men. The overarching goal of this project is to provide continuity in the organization of the study, continue the infrastructure for the MrOS project, allow for continued follow-up of the participants, and support the collection of limited study measurements. The specific aims of this project are to support the ongoing MrOS infrastructure. These include to 1) continue follow-up for MrOS participants for fractures, falls, mobility limitation and death; 2) collect repeat HR-pQCT scans in a subset of active MrOS participants; and 3) maintain the scientific organization for study communications; publications and ancillary review; and the public data release infrastructure. These aims will provide the critical framework required to address future scientific goals, such as characterization of the circumstances of fractures in the oldest old; quantification of change in peripheral bone microarchitecture by HR-pQCT and identification of determinants of that change; and determination of the utility of hip and spine CT based CT-FEA measures to predict fracture risk in older men.