Bone Strength Through the Menopausal Transition: Trabecular Bone Score

 描述(由申请者提供)：我们的奖助金建议竞争性更新，更年期骨强度：骨小梁评分，建立在全国妇女健康研究(天鹅)骨项目的基础上。SWAN是一项多地点、多种族/民族的纵向研究，旨在描述绝经过渡(MT)期间发生的生理和心理社会变化。Swan特别针对的卵巢老化的关键生理后果之一是骨骼质量的丧失。在Swan患者中，腰椎(LS)和股骨颈(FN)部位的面骨密度(ABMD)在末次月经期(FMP)前2年开始丢失。FMP治疗前1年至治疗后2年的累积骨量丢失速率最大，称为更年期。FMP减慢后2-5年骨丢失。与这一应用密切相关的是，经绝经后腰椎的骨密度丢失在腰椎比在FN更大，这与腰椎的骨小梁比例较高是一致的。我们还发现LS，而不是FN，aBMD与横穿MT的意外骨折相关，再次强调了小梁骨的潜在主导作用。然而，在SWAN中，我们目前仅限于双能X射线吸收法(DXA)测量骨密度，不能区分骨小梁和皮质骨。骨小梁评分(TBS)是由LS-DXA扫描获得的一种新的骨小梁结构指标。骨小梁的微结构是决定骨强度的关键因素。骨小梁变薄和骨小梁连通性丧失都会严重破坏结构的完整性，削弱骨骼。TBS与骨小梁结构的其他指标相关，并可预测绝经后妇女的骨折。我们的建议为在天鹅队列中纵向研究骨小梁结构提供了一个前所未有的经济高效的机会。没有其他研究在20年的时间跨度中连续进行LS aBMD，其中包括大样本中的整个MT。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个新的假说。本研究的具体目的是：(1)确定所有受试者在绝经前或围绝经期早期以及在或接近骨密度峰值时TBS的种族差异的方向和大小。(2)检验TBS的纵向变化率随年龄的变化以及与MT的关系(3)检验基线TBS与中年女性骨折发生率之间的关系。(4)研究糖尿病和胰岛素抵抗对女性横穿MT时TBS的影响。我们工作的中心宗旨是“超越BMD”。这项建议建立在我们最初的拨款基础上，我们在那里做出了次要的贡献，表明髋关节结构、生物力学和几何元素改善了风险分类。我们现在建议将重点放在LS小梁的微结构上，并测试快速的绝经后丢失是否优先影响可能导致不可修复的结构损伤的骨小梁。我们的长期目标是大幅提高我们对衰老、更年期和骨骼力量的理解。

 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.