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

项目总结/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一个 一个潜在的改变范式的问题：我们是否应该防止快速骨矿物质密度（BMD）下降期间， 绝经过渡期（MT）和绝经后早期（在BMD显著下降之前）， 后续骨折的风险 MT和早期绝经后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与骨形成之间的负平衡有助于快速BMD 衰退、骨微结构损伤和骨折风险。然而，在我们测试 早期干预，我们必须克服一个关键的障碍：我们必须能够预测一个妇女在她的 40 ~ 50岁是绝经后早期和绝经后早期骨密度快速下降和骨折的危险期。 这项研究的首要目标是通过检查一种新的骨平衡是否能解决这一障碍， 结合个体骨吸收和骨形成以非侵入性地估计骨平衡的BBI指数， 可预测BMD快速下降和骨折。我们将在2010年的妇女健康研究中进行这项研究。 天鹅（Swan）从天鹅，我们以前创建了一个概念验证的BBI使用骨转换标志物 不再推荐用于临床研究。BBI是BMD下降的一个更强的预测因子， 单独的骨吸收标记物。 在这里，我们将进一步发展BBI结构，以最大限度地提高其预测BMD下降的能力 和骨折我们建议在MT期间和早期从SWAN参与者中收集库存血清， 绝经后测量目前公认的参考骨吸收（血清胶原I型C- 端肽[s-CTX]）和形成（血清I型前胶原前肽[s-PINP]）标志物。然后我们将 用s-CTX和s-PINP重建我们的BBI目标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。目标2将检查BBI的能力， s-CTX预测BMD快速下降。目的3将检查BBI和s-CTX预测未来骨折的能力。 这些目标将为开发一种将BBI与临床风险因素（类似 在FRAX中将BMD添加到临床风险因素中），以确定可能从早期干预中受益的女性， 从而为检验早期、短期、预防性干预的功效的临床试验铺平道路。这 研究计划最终可能有助于我们预防骨折的方式发生转变：针对高血压， 在BMD显著下降之前，40 - 50岁的风险女性。

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.