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Predicting Fast Bone Mineral Density Decline and Fracture Across the Menopause Transition

预测更年期过渡期间骨矿物质密度的快速下降和骨折

基本信息

批准号：
10159847
负责人：
Albert Shieh
金额：
$ 41.49万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
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：
2020-05-06 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10159847
关键词：
Address Affect Blood Circulation Bone Density Bone Resorption C-telopeptide Clinical Research Clinical Trials Collagen Type I Cyclophosphamide Data Early Intervention Equilibrium Foundations Fracture Future High Risk Woman Individual Intervention Investigation Lead Life Longitudinal Studies Measures Menopause Menstruation N-telopeptide Osteocalcin Osteogenesis Ovarian aging Participant Postmenopause Prevention Probability Publishing Research Risk Risk Factors Serum Serum Markers Skeleton Study of Women&apos s Health Across the Nation Testing Time Translating Type I Procollagen Urine Woman Work bone bone loss bone turnover clinical risk disability efficacy testing experience fracture risk high risk improved indexing individual variation middle age mortality multi-racial novel osteoporosis with pathological fracture preservation prevent preventive intervention programs prospective racial and ethnic tool

项目摘要

PROJECT SUMMARY/ABSTRACT Osteoporotic fractures affect >1.4 million U.S. postmenopausal women annually, and contribute to loss of independence and mortality. This study aims to establish a foundation that will ultimately allow us to address a potentially paradigm-changing question: should we prevent fast bone mineral density (BMD) decline during the menopause transition (MT) and early postmenopause (before substantial BMD decline has occurred) to reduce the risk of subsequent fractures? The MT and early postmenopause may be opportune times for early, short-term intervention because increased bone turnover and negative balance between bone resorption and formation contribute to fast BMD decline, damage to bone microarchitecture and risk of fracture. However, before we can test the efficacy of early intervention, we must surmount a critical barrier: we have to be able to predict whether a woman in her 40s to 50s is at risk for fast BMD decline and fracture during the MT and early postmenopause. The overarching objective of this study is to tackle this barrier by examining whether a novel bone balance index (BBI) that combines individual bone resorption and formation to non-invasively estimate bone balance, can predict fast BMD decline and fracture. We will conduct this study in the Study of Women's Health Across the Nation (SWAN). From SWAN, we previously created a proof-of-concept BBI using bone turnover markers that are no longer recommended for clinical research. This BBI was a stronger predictor of BMD decline than a bone resorption marker alone. Here, we will further develop the BBI construct, in an effort to maximize its ability to predict BMD decline and fracture. We propose to access banked serum collected from SWAN participants during the MT and early postmenopause to measure currently acknowledged reference bone resorption (serum collagen type I C- telopeptide [s-CTX]) and formation (serum procollagen type I propeptide [s-PINP]) markers. We will then recreate our BBI using s-CTX and s-PINP. Aim 1 will characterize how s-CTX, s-PINP, and BBI (created from s-CTX and s-PINP) change during the MT and early postmenopause. Aim 2 will examine the ability of BBI and s-CTX to predict fast BMD decline. Aim 3 will examine the ability of BBI and s-CTX to predict future fracture. These aims will lay the foundation for developing a tool that combines BBI with clinical risk factors (similar to adding BMD to clinical risk factors in FRAX) to identify women who may benefit from early intervention, and thus pave the way for clinical trials testing the efficacy of early, short-term, preventive intervention. This program of investigation could ultimately contribute to a shift in the way that we prevent fracture: targeting high- risk women in their 40s-50s prior to substantial BMD decline.

项目总结/文摘