Laxity and Malalignment in a Large Cohort Study of OA

描述（由申请人提供）：膝关节OA是美国老年人慢性残疾的主要原因。由于对相关因素的了解有限，几乎没有预防膝关节骨性关节炎发生、进展或残疾的策略。人们越来越认识到膝关节松弛和对线不良的作用，这两个潜在的可改变因素是当前应用的焦点。这些因素正在西北大学进行的300名受试者MAK研究（膝关节炎的机械因素）中进行检查，其中获得了广泛的经验，并积累了其重要性的证据。 现在提出的是一项综合检查松弛和对线不良对患有膝关节骨性关节炎或具有发生膝关节骨性关节炎高风险的受试者的影响，作为最近资助的多中心骨性关节炎研究（MOST）的辅助研究。MOST是一项纳入3000名男性和女性的研究，主要目的是检查一组风险因素对OA结局的影响，为期3年。MOST涉及4个研究中心：协调和MRI阅读中心（UCSF）、数据分析和X线阅读中心（BU）以及2个临床中心（UAB和UI）。 本申请的假设重点关注松弛和对线不良是否各自与以下因素相关：与非松弛膝关节和对线更中性的膝关节相比，OA事件风险更高;身体功能下降; OA进展风险。主要假设集中在症状和X线结果;还提出了基于MRI的软骨形态评估，作为在MOST队列的子集中检查这些因素中的每一个的隔室特异性效应的手段。 要求提供支助的有：在MOST中复制测量系统和协议，（用于松弛和对齐）;在MOST的基线检查时评估松弛和对齐;在队列的一个子集中，在基线和3年随访时使用高场扫描仪获得MRI，以检查软骨体积和厚度的变化作为松弛和对齐不良的结果;并测试松弛和对线不良与重要OA结局风险的关系。

DESCRIPTION (provided by applicant): Knee OA is a leading cause of chronic disability in older Americans. Few strategies to prevent knee OA development, progression, or disability exist, due to limited knowledge of the responsible factors. There has been increasing recognition of the role of knee laxity and malalignment, two potentially modifiable factors that are the focus of the current application. These factors are being examined in the ongoing 300-subject MAK study (Mechanical Factors in Arthritis of the Knee) at Northwestern University, in which extensive experience has been gained with them, and evidence of their importance has accumulated. Now proposed is a comprehensive examination of the effect of laxity and malalignment in subjects with or at high risk to develop knee OA, as an ancillary study to the recently funded Multicenter OA Study (MOST). MOST is a study of 3000 men and women, with the primary goal of examining the effect of a panel of risk factors on OA outcomes over 3 years. MOST involves 4 sites: the Coordinating and MRI Reading Center (UCSF), Data Analysis and X-ray Reading Center (BU), and 2 Clinical Centers (UAB and UI). Hypotheses of this application focus on whether laxity and malalignment are each associated with: a higher risk of incident OA than non-lax knees and more neutrally aligned knees; a decline in physical function; risk of OA progression. Primary hypotheses focus on symptom and x-ray outcomes; MRI-based assessment of cartilage morphology is also proposed as a means of examining the compartment-specific effects of each of these factors in a subset of the MOST cohort. Support is requested: to replicate in MOST the measurement systems and protocols (for laxity and alignment) currently in use in the MAK study; to assess laxity and alignment at the baseline exam of MOST; in a subset of the cohort, to obtain MRI at baseline and at 3 year follow-up using a high-field scanner to examine change in cartilage volume and thickness as outcomes of laxity and malalignment; and to test the relationship of laxity and malalignment with risk of important OA outcomes.