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，很明显，不存在改善OA疾病的医学补救措施，即使类似的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。然而，与骨质疏松症相反，没有既定的生物标志物可以在早期阶段检测出高危个体并随时间推移对其进行随访。这一直是膝关节OA疾病改善干预措施开发的主要障碍。测量特定区域胫骨关节周围骨密度（paBMD）是一种新的双能X线吸收测定（DXA）技术，最近出现的潜在的生物标志物为膝关节OA。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的定量可以快速进行，并且在训练有素的技术人员手中具有高度的重现性。我们有四个目标：（1）显示胫骨paBMD作为X线检查OA和相关慢性疼痛发生风险的指标，（2）使用复杂的统计方法计算个体发生膝关节OA的风险水平，（3）确定胫骨paBMD是否预测未患OA的膝关节中的纵向软骨体积损失，以及（4）测试胫骨paBMD与MRI扫描所见的关节周围骨中OA特征（如骨磨损）的相关性（邻近软骨的骨变平或凹陷），骨髓病变（水敏MRI序列上骨髓中的高信号区域）、骨赘和软骨下囊肿。我们将通过提出一个正在进行的骨关节炎倡议（OAI）研究的辅助项目来实现这些目标，该研究为膝关节OA高风险人群提供常规的广泛年度评估，包括X线和3-T MRI（但尚未DXA）。如果我们能够证明胫骨paBMD是膝关节OA的良好生物标志物，这将使我们朝着找到有效的膝关节OA疾病改善治疗方法迈出重要一步。

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.