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

• 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
• 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' 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

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.

项目摘要/摘要 骨质疏松性骨折每年影响> 140万美国的绝经后妇女，并导致失去 独立性和死亡率。这项研究旨在建立一个基础，最终使我们能够解决 可能改变范式的问题：我们是否应防止快速骨矿物质密度（BMD）下降 更年期过渡（MT）和术后早期（在大幅下降之前）减少 随后骨折的风险？ MT和绝经后早期可能是早期，短期干预的适当时间，因为 骨吸收和形成之间的骨骼更新和负平衡增加有助于快速BMD 下降，对骨微结构的损害和骨折的风险。但是，在我们测试的功效之前 早期干预，我们必须克服一个关键的障碍：我们必须能够预测她是否在她身上 40至50年代在MT和绝经后早期的快速BMD下降和骨折的风险。 这项研究的总体目的是通过检查新的骨头平衡来应对这一障碍 将单个骨吸收和形成与非侵入性估计骨平衡相结合的索引（BBI）， 可以预测快速的BMD下降和断裂。我们将在研究妇女健康的研究中进行这项研究 国家（天鹅）。从天鹅那里，我们以前使用骨转换标记创建了概念证明BBI 不再建议进行临床研究。该BBI比A比 仅骨吸收标记。 在这里，我们将进一步开发BBI结构，以最大程度地预测BMD下降的能力 和断裂。我们建议在MT和早期访问从天鹅参与者那里收集的银行血清 结肠后期要测量当前确认的参考骨吸收（血清胶原蛋白I型C-） 端肽[S-CTX]）和形成（血清Procollagen I型丙肽[S-PINP]）标记。然后我们会 使用S-CTX和S-PINP重新创建我们的BBI。 AIM 1将表征S-CTX，S-PINP和BBI（由 S-CTX和S-PINP）在MT和绝经后早期变化。 AIM 2将检查BBI和 S-CTX预测快速BMD的下降。 AIM 3将检查BBI和S-CTX预测未来断裂的能力。 这些目标将为开发一种将BBI与临床风险因素结合起来的工具奠定基础（类似 将BMD添加到Frax的临床危险因素中），以确定可能从早期干预中受益的妇女，并且 因此，为临床试验铺平了道路测试早期，短期，预防性干预的功效。这 调查计划最终可能会导致我们预防骨折的方式的转变：针对高 在BMD大幅下降之前，有40年代至50年代的妇女冒险。