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Changes in Periosteal and Endocortical Width Across the Menopausal Transition

更年期过渡期间骨膜和皮质内宽度的变化

基本信息

批准号：
10458655
负责人：
KARL J JEPSEN
金额：
$ 43.41万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10458655
关键词：
Address Adult Affect Aging Algorithmic Analysis Area Biological Biological Testing Bone Density Bone Mineral Contents Bone structure Cadaver Clinical Data Diagnosis Dual-Energy X-Ray Absorptiometry Early Intervention Epidemiology Femur Fracture Goals Hand Hip region structure Histologic Hormonal Change Human Image Individual Individual Differences Knowledge Longitudinal cohort Masks Menopause Metacarpal bone Michigan Neck Osteoporosis Phase Physicians Porosity Postmenopause Prevention strategy Property Prophylactic treatment Public Health Research Risk Sampling Site Skeletal system Structure Study of Women&apos s Health Across the Nation Testing Tissues Variant Weight-Bearing state Width Woman Work age related base black women bone bone health bone loss bone mass bone metabolism bone strength cohort critical period disability economic cost fracture risk fragility fracture hip bone human study indexing insight longitudinal database men metabolic abnormality assessment morphogens rate of change tibia trait treatment strategy young adult

项目摘要

Project Summary For women, the menopausal transition (MT) is a critical period of decline in bone strength, during which about half the lifetime loss in bone mineral density (BMD) occurs. While clinically, and in research, BMD is the primary indicator for osteoporosis, it does not reveal the changes in bone structure needed to fully understand age-related loss in strength. This proposal seeks to better elucidate the structural changes that underlie loss in strength during the MT by examining relative changes in endocortical expansion (bone loss) versus periosteal expansion (bone gain). These two features define bone strength, but the manner in which each of these structural indices changes during the MT is largely unexplored. Our central hypothesis is that bone strength declines earlier and more rapidly in women with wide bones compared to women with narrow bones. This hypothesis is guided by promising preliminary data findings in our epidemiologic and cadaver studies which suggest that individualized trajectories of strength-decline may be established during the initial phase of bone loss for women, and that external bone size (e.g., bone width, total cross-sectional area) may identify women in a high fracture-risk group. We will first validate new bone strength indices and test for the biological basis of our hypothesis in cadaveric tissue (Aim 1). Our work in cadaveric tissue has shown greater intra-cortical porosity in wide compared to narrow bones, suggesting different strength-decline trajectories may arise from BMU-based remodeling. Because this can only be studied precisely using histological sections, we will combine cadaveric studies (Aim 1) with living human studies (Aims 2,3) to provide a biological basis for observations derived from longitudinal data. We will test our central hypothesis using two existing longitudinal databases with image-data acquired over 20 years among 40-60 year-old women as they transition from pre- to post-menopause. We will relate baseline bone traits to structural and strength changes during the MT in a weight-bearing, fracture prone bone (proximal femur) and a nonweight-bearing, non-fracture prone bone (metacarpal) to assess its clinical value for diagnosing strength changes at the hip. Specifically, we propose to 1) test for associations between baseline external bone size and changes in strength indices during the MT for white women in the Michigan Bone Health and Metabolism Study (MBHMS) and then 2) test whether the factors that differentiate between white women who lose more vs. less bone strength during the MT in the MBHMS are predictive of MT-related strength declines in white and black women followed across the MT over 20 years in the Study of Women’s Health Across the Nation (SWAN). This study addresses a significant gap in scientific knowledge that impedes our ability to optimize fracture prevention strategies. If our hypotheses prove correct, baseline external bone size may be used as an additional parameter to identify women most likely to lose bone strength rapidly during the MT and who might benefit from early intervention. Successful completion of our Aims will provide fundamental new information about what specific structural and material parameters can best inform clinical decisions.

项目总结

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

External bone size identifies different strength-decline trajectories for the male human femora.

外部骨骼大小可以识别男性人类股骨的不同强度轨迹轨迹。

DOI：
10.1016/j.jsb.2020.107650
发表时间：
2020-12-01
期刊：
Journal of structural biology
影响因子：
3
作者：
Bolger MW;Romanowicz GE;Bigelow EMR;Ward FS;Ciarelli A;Jepsen KJ;Kohn DH
通讯作者：
Kohn DH

The effect of low-trauma fracture on one-year mortality rate among privately insured adults with and without neurodevelopmental disabilities.

低创伤性骨折对有或没有神经发育障碍的私人保险成年人一年死亡率的影响。

DOI：
10.1016/j.bone.2019.115060
发表时间：
2019
期刊：
Bone
影响因子：
4.1
作者：
Whitney,DanielG;Whibley,Daniel;Jepsen,KarlJ
通讯作者：
Jepsen,KarlJ

Region-specific associations among tissue-level mechanical properties, porosity, and composition in human male femora.

人类男性股骨组织级机械性能、孔隙率和成分之间的区域特异性关联。

DOI：
10.1016/j.jbiomech.2022.111144
发表时间：
2022-06
期刊：
JOURNAL OF BIOMECHANICS
影响因子：
2.4
作者：
Mandair, Gurjit S.;Bigelow, Erin M. R.;Viswanathan, Gowri;Ward, Ferrous S.;Patton, Daniella M.;Schlecht, Stephen H.;Jepsen, Karl J.;Kohn, David H.
通讯作者：
Kohn, David H.

Elevated fracture risk for adults with neurodevelopmental disabilities.

DOI：
10.1016/j.bone.2019.115080
发表时间：
2020-01
期刊：
Bone
影响因子：
4.1
作者：
Whitney DG;Caird MS;Jepsen KJ;Kamdar NS;Marsack-Topolewski CN;Hurvitz EA;Peterson MD
通讯作者：
Peterson MD

Sex and External Size Specific Limitations in Assessing Bone Health From Adult Hand Radiographs.