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

项目摘要/摘要 骨质疏松性骨折每年影响140万美国绝经后妇女，并导致 独立和死亡。这项研究旨在建立一个基础，最终使我们能够解决 潜在的改变范式的问题：我们是否应该防止骨密度(BMD)在 绝经过渡(MT)和绝经后早期(在BMD大幅下降之前)以减少 后续骨折的风险有多大？ MT和绝经后早期可能是早期、短期干预的合适时机，因为 骨转换增加和骨吸收和骨形成之间的负平衡导致快速骨密度 下降，对骨骼微结构的损害和骨折的风险。然而，在我们可以测试 早期干预，我们必须跨越一个关键的障碍：我们要能够预测一个女人是否在她 在MT和绝经早期，40-50岁的女性有骨密度快速下降和骨折的风险。 这项研究的首要目标是通过检查一种新的骨骼平衡 结合个体骨吸收和骨形成的指数(BBI)，非侵入性地估计骨平衡， 可以预测骨密度快速下降和骨折。我们将在妇女健康研究中进行这项研究 国家(天鹅)。在Swan之前，我们使用骨转换标记创建了一个概念验证BBI 不再推荐用于临床研究的药物。BBI是骨密度下降的更强的预测指标，而不是 单独的骨吸收标志物。 在这里，我们将进一步发展BBI结构，努力使其最大限度地预测BMD下降的能力 和骨折。我们建议访问在MT期间和早期从Swan参与者那里收集的银行血清 绝经后测量目前公认的参考骨吸收(血清型胶原-C- 端肽(S-环磷酰胺)和形成(血清I型前胶原前肽[S-PINP])标志物。到时候我们会的 使用S-CTX和S-PINP重建我们的BBI。目标1将描述S-CTX、S-PINP和BBI(创建自 S-环磷酰胺和S-平阳霉素)在MT和绝经早期的变化。目标2将检查BBI和 S预测骨密度快速下降。目的3将检查脑BI和S-CTX对未来骨折的预测能力。 这些目标将为开发将BBI与临床风险因素(类似)相结合的工具奠定基础 将骨密度添加到FRAX的临床危险因素中)，以确定哪些女性可能从早期干预中受益，以及 从而为临床试验检验早期、短期、预防性干预的效果铺平道路。这 调查计划最终可能有助于改变我们预防骨折的方式：瞄准高位骨折 40-50多岁的女性在骨密度大幅下降之前存在风险。

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.