Bone Strength Through the Menopausal Transition: Trabecular Bone Score

 描述（由申请人提供）：我们的赠款，骨强度通过月经过渡：骨小梁评分，建议竞争性更新，建立在全国妇女健康研究（天鹅）骨项目。SWAN是一项多中心、多种族/民族纵向研究，旨在描述绝经过渡期（MT）期间发生的生理和心理变化。卵巢衰老的一个关键生理后果是骨骼质量的损失，这是专门针对SWAN的。在SWAN中，腰椎（LS）和股骨颈（FN）部位的面积骨矿物质密度（aBMD）损失在末次月经（FMP）前2年开始。从FMP前1年到FMP后2年的累积骨丢失率最高，称为绝经期。FMP后2-5年骨丢失减缓。根据本申请，LS的绝经后BMD损失大于FN，这与LS中小梁骨的比例较高一致。我们还发现LS，而非FN，aBMD与整个MT的偶发骨折相关，再次强调了骨小梁的潜在主导作用。然而，在SWAN中，我们目前仅限于双能X线吸收法（DXA）测量aBMD，无法区分骨小梁和皮质骨。骨小梁评分（TBS）是一种新的骨小梁结构指标，可通过LS DXA扫描获得。骨小梁的微结构是骨强度的关键决定因素。骨小梁变薄和骨小梁连接性丧失实质上破坏了结构完整性并削弱了骨。TBS与骨小梁结构的其他指标相关，可预测绝经后妇女的骨折。我们的建议提供了一个前所未有的具有成本效益的机会，调查骨小梁结构纵向天鹅队列。没有其他研究LS aBMD连续20年的时间跨度，包括整个MT在一个大的多种族样本。通过重新分析SWAN脊柱DXA扫描以获得TBS，我们有独特的机会分离小梁微结构并测试几种新的假设。本研究的具体目的是：（1）当所有参与者处于绝经前或围绝经期早期，处于或接近峰值BMD时，确定基线时TBS的种族差异的方向和幅度。（2）检查TBS随年龄增长和MT的纵向变化率（3）检查基线TBS与中年女性发生骨折之间的相关性。（4）检查糖尿病和胰岛素抵抗在基线和纵向上对女性穿越MT的TBS的影响。我们工作的中心原则是“超越弹道导弹防御”。该提案建立在我们最初的资助基础上，我们做出了实质性的贡献，表明髋关节结构、生物力学和几何要素可以改善风险分类。我们现在建议关注LS骨小梁微结构，并测试快速绝经后骨丢失是否优先影响骨小梁，这可能导致不可修复的结构损伤。我们的长期目标是大大提高我们对衰老，更年期和骨骼强度的理解。

 DESCRIPTION (provided by applicant): The proposed competitive renewal of our grant, Bone Strength Through the Menopausal Transition: Trabecular Bone Score, builds upon the Study of Women's Health Across the Nation (SWAN) Bone Project. SWAN is a multi-site, multi-racial/ethnic longitudinal study designed to characterize the physiological and psychosocial changes that occur during the menopausal transition (MT). One of the key physiological consequences of ovarian aging that was specifically targeted in SWAN was loss in skeletal mass. In SWAN, areal bone mineral density (aBMD) loss begins 2 years before the final menstrual period (FMP) at both the lumbar spine (LS) and femoral neck (FN) sites. Cumulative rates of bone loss are greatest from 1 year before through 2 years after the FMP, termed the transmenopause. Bone loss 2-5 years after the FMP slows. Germane to this application, transmenopausal BMD loss is greater at the LS than at FN, concordant with the higher proportion of trabecular bone in the LS. We also found that LS, but not FN, aBMD was associated with incident fractures across the MT, again emphasizing the potential dominant role of trabecular bone. However, in SWAN we are currently limited to dual-energy x-ray absorptiometry (DXA) measures of aBMD which cannot distinguish trabecular and cortical bone. The trabecular bone score (TBS) is a new index of trabecular bone structure that can be obtained from LS DXA scans. Microarchitecture of trabecular bone is a key determinant of bone strength. Both thinning of trabeculae and loss of trabecular connectivity substantially undermines structural integrity and weakens bone. TBS is associated with other measures of trabecular bone structure and predicts fracture in postmenopausal women. Our proposal offers an unprecedented cost-efficient opportunity to investigate trabecular bone structure longitudinally in the SWAN cohort. No other study has LS aBMD serially for a 20- year time span that includes the entire MT in a large multiracial sample. By reanalyzing SWAN spine DXA scans to obtain TBS we have the unique opportunity to isolate trabecular microarchitecture and test several novel hypotheses. The specific aims of our study are to: (1)Determine the direction and magnitude of ethnic difference in TBS at baseline when all participants were either premenopausal or early perimenopausal and so at or near their peak BMD. (2)Examine the rate of longitudinal change in TBS with aging and with the MT (3) Examine the association between baseline TBS and incident fractures in midlife women. (4)Examine the effect of diabetes and insulin resistance on TBS at baseline and longitudinally as women traverse the MT. The central tenet of our work is "beyond aBMD". This proposal builds on our initial grant where we made sub- stantial contributions showing that hip structural, biomechanical and geometric elements improves risk class- ification. We now propose to focus on LS trabecular microarchitecture and test whether the rapid trans- menopausal loss preferentially effects trabecular bone which could lead to irreparable structure damage. Our long term objective is to substantially improve our understanding of aging, menopause and skeletal strength.