Periarticular Bone Density as a Biomarker for Early Knee OA

描述(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，尽管类似的与年龄相关的肌肉骨骼疾病--骨质疏松症--并受益于几种有效的治疗方法，但目前尚无治疗骨性关节炎的医学疗法。然而，与骨质疏松症不同的是，没有既定的生物标记物来在早期阶段发现高危个体并跟踪他们一段时间。这一直是膝骨性关节炎疾病修正干预措施发展的主要障碍。区域特异性胫骨关节周围骨密度(PaBMD)的测量是双能X射线骨密度仪(DXA)技术的一种新应用，该技术最近出现，有可能成为膝骨性关节炎的生物标志物。重要的是，DXA扫描仪无处不在，操作简单，相对无害，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可重复性。我们的目标有四个方面：(1)显示胫骨paBMD是X射线上显示的骨关节炎和相关慢性疼痛的风险指标，(2)使用复杂的统计学方法来计算个人患膝骨性关节炎的风险水平，(3)确定胫骨paBMD是否可以预测不患有骨性关节炎的膝关节的纵向软骨体积损失，以及(4)测试胫骨paBMD与关节周围骨的特征，例如骨磨损(软骨附近的骨变平或凹陷)的相关性。骨髓病变(在水敏感的MRI序列上看到的骨髓高信号区)、骨赘和软骨下囊肿。为了实现这些目标，我们将提出一个正在进行的骨关节炎倡议(OAI)研究的辅助项目，该研究为膝骨性关节炎的高危人群提供常规的广泛年度评估，包括X光和3-T MRI(但尚未进行DXA)。如果我们能够证明胫骨paBMD是膝骨性关节炎的一个很好的生物标志物，这将使我们朝着找到有效的膝骨性骨性关节炎的疾病修正治疗迈出重要的一步。 公共卫生相关性：骨关节炎(OA)是一个重要的公共卫生问题，因为它是老年人中最致残的疾病之一，但有效的治疗方法有限。如果我们能够证明膝关节骨密度扫描是早期膝骨性关节炎的一个很好的生物标志物，这将使我们朝着找到针对这种疾病的有效的疾病修正治疗更近一步。

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. PUBLIC HEALTH RELEVANCE: 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. If we are able to show that a knee bone density scan is a good biomarker for early knee OA, this will take us an important step closer towards finding an effective disease- modifying treatment for this condition.