Periarticular Bone Density as a Biomarker for Early Knee OA

描述（由申请人提供）：骨关节炎（OA）是一个重要的公共卫生问题，因为它是老年人最致残的疾病之一，但有效的治疗方法有限。因此，值得注意的是，尽管骨性关节炎是一种类似的与年龄相关的肌肉骨骼疾病，骨质疏松症，并从几种有效的治疗中获益，但目前还没有针对骨性关节炎的治疗方法。然而，与骨质疏松症不同的是，目前还没有确定的生物标志物可以在早期阶段检测出有风险的个体，并对其进行长期跟踪。这一直是发展疾病改善干预膝关节OA的主要障碍。测量区域特异性胫骨关节周围骨矿物质密度（paBMD）是双能x射线吸收仪（DXA）技术的一种新应用，最近出现了作为膝关节OA生物标志物的潜力。重要的是，DXA扫描仪无处不在，易于操作，相对无害且价格低廉；此外，胫骨paBMD的定量可以在训练有素的技术人员手中快速进行，并且具有很高的可重复性。我们的目标有四个方面：(1)显示胫骨paBMD作为风险指标对x射线和办公自动化的发展相关的慢性疼痛,(2)使用复杂的统计方法计算的风险级别个体发展中膝关节OA(3)确定胫骨paBMD预测纵向膝盖软骨体积亏损,没有办公,和(4)测试协会的胫骨paBMD特性的OA peri-articular骨出现在核磁共振扫描,如骨磨损（软骨附近的骨变平或凹陷）、骨髓病变（水敏感MRI序列上可见的骨髓高信号区域）、骨赘和软骨下囊肿。我们将通过提出一个辅助项目来实现这些目标，该项目为正在进行的骨关节炎倡议（OAI）研究提供常规的广泛的年度评估，包括x射线和3-T MRI（但尚未DXA），用于发展为膝关节OA的高风险人群。如果我们能够证明胫骨paBMD是膝关节OA的良好生物标志物，这将使我们朝着寻找有效的膝关节OA疾病改善治疗方法迈出重要的一步。

DESCRIPTION (provided by applicant): Osteoarthritis (OA) is an important public health problem as it is one of the most disabling diseases in the elderly but effective treatments are limited. It is, therefore, salient that no disease-modifying medical remedies for OA exist, even though an analogous age-related musculoskeletal disorder, osteoporosis, and benefits from several effective treatments. However, and in contrast to osteoporosis, there is no established biomarker to detect at-risk individuals at an early stage and to follow them over time. This has been a primary obstacle to the development of disease-modifying interventions for knee OA. Measurement of region-specific tibial periarticular bone mineral density (paBMD) is a novel utilization of dual energy X-ray absorptiometry (DXA) technology that has recently emerged with potential as a biomarker for knee OA. Importantly, DXA scanners are ubiquitous, easy to operate, relatively non-hazardous and inexpensive; further, quantitation of tibial paBMD can be performed quickly and is highly reproducible in the hands of well-trained technicians. Our goals are four fold: (1) to show that tibial paBMD as an indicator of risk for the development of OA on X-ray and related chronic pain, (2) to use sophisticated statistical methods to calculate the level of risk an individual has of developing knee OA (3) to determine whether tibial paBMD predicts longitudinal cartilage volume loss in knees that do not have OA, and (4) to test the association of tibial paBMD with features of OA in the peri-articular bone seen on MRI scans, such as bone attrition (flattening or depression of bone adjacent to cartilage) , bone marrow lesions (regions of high signal in the bone marrow seen on water sensitive MRI sequences), osteophytes and subchondral cysts. We will pursue these aims by proposing an ancillary project to the outstanding ongoing Osteoarthritis Initiative (OAI) Study that provides routine extensive annual evaluations including x-rays and 3-T MRI (but not yet DXA) in people at high risk for the development of knee OA. If we are able to show that tibial paBMD is a good biomarker for knee OA, this will take us an important step closer towards finding an effective disease-modifying treatment for knee OA.