Volumetric Bone Density and Vascular Calcification: The Framingham QCT Study

描述（由申请人提供）：Elizabeth J. Samelson博士是一位训练有素的肌肉骨骼流行病学家，计划开发新的技能和专业知识来研究骨质疏松症和血管钙化之间关系的潜在共享机制。具体来说，拟议的培训和研究计划的直接职业目标是让候选人在两个领域发展新的技能和知识：(1)骨骼和血管钙化的生物学；(2)使用定量计算机断层扫描（QCT）骨密度测量技术来研究骨骼和血管钙化之间的关系。候选人的长期职业目标是成为肌肉骨骼疾病领域的独立研究者和骨骼和血管钙化（一个新的和知之甚少的领域）的专家，最终的公共卫生目标是帮助降低骨质疏松症（可能还包括动脉粥样硬化）的风险及其对老年妇女和男性的破坏性影响。研究生涯发展计划包括与独立资助的导师、在骨质疏松流行病学、血管钙化和骨成像方面具有综合和互补专业领域和项目的高级研究人员进行频繁的正式互动。培训将包括参加在波士顿优秀的研究环境中进行的密集、全面的课程和跨学科研究研讨会，包括希伯来老年生活研究所（HSL）的老龄化研究所（IFAR）、哈佛医学院（HMS）及其附属机构（Beth Israel Deaconess医疗中心、马萨诸塞州总医院）以及弗雷明汉研究。本研究的目的是使用Framingham QCT研究（一项大型社区研究，涉及1800名男性和1700名女性，年龄40至90岁，平均61岁）的3500名参与者的QCT图像来确定脊柱的体积、骨小梁骨矿物质密度（vTBMD），并评估vTBMD水平与血管钙化严重程度之间的关系（在相同的扫描中评估）。该研究将使用可靠的、经过验证的技术来分析QCT图像，并将这些数据与Framingham参与者严格获得的临床信息相结合。最后，本研究将验证vTBMD与血清骨保护素（osteoprotegerin， OPG）水平呈正相关，与核因子k - β配体受体激活因子（receptor activator of nuclear factor K-beta ligand， RANKL）水平呈负相关的假设，并且OPG将解释男女vTBMD与血管钙化呈负相关的比例具有统计学意义。提出的研究的相关性在于，其结果将提高对骨质疏松症的可能原因的理解，骨质疏松症也与心血管疾病的发展有关。因此，这项研究的结果可能会导致未来治疗骨质疏松症和心血管疾病。

DESCRIPTION (provided by applicant): Elizabeth J. Samelson, PhD, is a well-trained musculoskeletal epidemiologist planning to develop new skills and expertise to investigate potential shared mechanisms underlying the relation between osteoporosis and vascular calcification. Specifically, the immediate career goal of the proposed training and research program is for the candidate to develop new skills and knowledge in two areas: (1) the biology of bone and vascular calcification and (2) the use of quantitative compute tomography (QCT) bone densitometry techniques to investigate the relation between bone and vascular calcification. The long-term career goal is for the candidate to become an independent investigator in the area of musculoskeletal disease and an expert in bone and vascular calcification, a new and poorly understood area, with the ultimate public health goal to help reduce the risk of osteoporosis (and possibly, in conjunction, atherosclerosis) and its devastating impact on elderly women and men. The research career development plan involves frequent, formal interactions with mentors who are independently funded, senior investigators with comprehensive and complementary areas of expertise and programs in osteoporosis epidemiology, vascular calcification, and bone imaging. Training will include participation in intensive, comprehensive courses and interdisciplinary research seminars conducted in the outstanding research environment in Boston, including the Institute for Aging Research (IFAR) at Hebrew SeniorLife (HSL), Harvard Medical School (HMS) and its affiliated institutions (Beth Israel Deaconess Medical Center, Massachusetts General Hospital), as well as the Framingham Study. The purpose of this study is to use QCT images performed in 3500 participants of the Framingham QCT Study (a large, community-based study of 1800 men and 1700 women, ages 40 through 90 years, mean 61 years) to determine volumetric, trabecular bone mineral density (vTBMD) of the spine and assess the relation between vTBMD level and severity of vascular calcification (assessed on the same scans). The study will use reliable, validated techniques to analyze the QCT images and combine these data with clinical information rigorously acquired for Framingham participants. Finally, the study will test the hypothesis that vTBMD will be positively related to serum level of osteoprotegerin (OPG), and inversely related to receptor activator of nuclear factor K-beta ligand (RANKL), and that OPG will explain a statistically significant proportion of the inverse correlation between vTBMD and vascular calcification in women and men. The relevance of the proposed study is that the results will improve understanding of the possible causes of osteoporosis also involved with the development of cardiovascular disease. Thus, the results of this study could lead to future therapies to treat and or event both osteoporosis and cardiovascular disease.