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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

基本信息

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
项目类别：
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

项目摘要

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.

在这个竞争性修订应用程序中，我们的目标是解决三个关键目标，以了解决定因素