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

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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.