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

摘要 骨折以及由此造成的发病率、死亡率和费用是老年男子日益沉重的负担。骨折率在65岁以后呈指数增长，髋部骨折的平均年龄>80岁。老年人骨折的风险受到骨密度、结构和强度长期下降的强烈影响，在此期间骨骼变化加速。 男性骨质疏松性骨折研究（MrOS）是一项正在进行的老年男性骨质疏松性骨折风险因素的前瞻性研究。这项研究继续跟踪最初在2000-2年登记的男性。MrOS是年龄最大的男性的最佳表型队列-现在在生命的第9和第10个十年-当骨折是维持独立的主要威胁时。20多年前，我们开始获得系列DXA测量并完成临床表型分型。 在基线时，获得髋关节和脊柱CT扫描（N=3695），以评估骨结构和强度。同样，2014-6年在大量男性（N=1831）中获得了HR-pQCT（XtremeCTII）扫描。因此，MrOS仍然是关于男性肌肉骨骼衰老的数据和发现的唯一来源，并且特别适合于解决关于老年男性骨骼脆弱性的几个关键临床和机械知识差距。该研究的全面骨成像，长期随访和队列的年龄非常大，提供了无与伦比的机会来生成设计有效方法所需的新信息，以减少老年男性的骨折负担。 本项目的总体目标是提供研究组织的连续性，继续MrOS项目的基础设施，允许对参与者进行持续随访，并支持收集有限的研究测量结果。 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）继续随访MrOS受试者的骨折、福尔斯、活动受限和死亡; 2）收集活跃MrOS受试者子集的重复HR-pQCT扫描; 3）维护研究通信、出版物和辅助审查的科学组织;以及公共数据发布基础设施。 这些目标将提供解决未来科学目标所需的关键框架，例如最年长老年人骨折情况的表征;通过HR-pQCT量化外周骨微结构变化并确定该变化的决定因素;以及确定基于髋关节和脊柱CT的CT-FEA措施预测老年男性骨折风险的实用性。

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.