Predictors and Consequences of Subchondral Bone Attrition in Osteoarthritis

描述(由申请人提供)：我是一名风湿科医生，在波士顿大学医学院大卫·T·费尔森博士的指导下进行研究培训。我还在攻读流行病学博士学位。我目前的职业目标是接受进一步的临床研究培训，以确立自己作为一名独立研究员的地位。我的长期目标是继续担任临床科学家的学术职位，专注于风湿病的流行病学研究。目前，我的兴趣集中在研究骨关节炎的病理生理因素，特别是与骨健康相关的因素。 费尔森博士和他的研究团队在办公自动化研究方面有着良好的记录，并在该领域做出了许多重要贡献。在这种研究环境下，我已经开始与莎拉·布斯博士合作，探索维生素K与骨影响之间的联系，她是这项拟议研究的合作者之一。这项拟议的研究将扩展这一合作，通过关注与骨关节炎软骨下骨磨损相关的因素来研究骨关节炎的其他方面。骨关节炎软骨下骨表面凹陷与大体骨折无关。软骨下骨被认为在骨性关节炎的疼痛和进展中起着重要作用。软骨下骨性质的改变可能反映了机械和系统因素。我们建议使用为期30个月的大型前瞻性队列多中心骨关节炎研究(MOST)的1600名参与者的数据，研究膝关节MRI上软骨下骨磨损与肢体对线/骨密度的关系，以及血液中与骨健康相关的营养因素(维生素D和K)，以及这些因素之间的相互作用。我们还建议检查软骨下骨磨损与MRI上软骨缺损的关系，以及与膝关节疼痛的关系。因此，这项研究建议检查对骨性关节炎的发展和进展的潜在贡献者，并确定治疗策略的潜在靶点。 相关：骨性关节炎是最常见的一种关节炎，目前尚无有效的治疗方法。鉴于我们的人口老龄化，这构成了一个重大的公共卫生问题。如果我们确定是机械和系统因素相互作用导致了骨性关节炎的异常，这将表明必须同时针对系统和机械方面来成功地治疗骨性关节炎，包括可能的抗吸收治疗和维生素D和K的补充剂与膝关节支架的结合。

DESCRIPTION (provided by applicant): I am a rheumatologist who is undertaking research training under the mentorship of Dr. David T. Felson at Boston University School of Medicine. I am also pursuing a doctoral degree in Epidemiology. My immediate career goals are to pursue further clinical research training to establish myself as an independent investigator. My long-term goals are to continue in an academic position as a clinician scientist, with a research career focused on epidemiologic study of rheumatic diseases. At present, my interests lie in studying pathophysiologic contributors to osteoarthritis (OA), and in particular, factors related to bone health in OA. Dr. Felson and his research team have a proven track-record in OA research and have made numerous important contributions to the field. In this research environment, I've already begun to explore the association of vitamin K, a nutritional factor with bone effects, with OA in collaboration with Dr. Sarah Booth, a collaborator on this proposed study. This proposed study will extend this collaboration to study additional aspects of OA by focusing on factors that are associated with subchondral bone attrition in OA, which is a depression of the subchondral bony surface unrelated to gross fracture. Subchondral bone is thought to play an important role in both the pain and progression of OA. The altered properties of subchondral bone likely reflect both mechanical and systemic factors. We propose examining the relation of subchondral bone attrition on knee MRI with limb alignment/bone mineral density, and nutritional factors related to bone health measured in blood (vitamins D and K), and the interaction of these factors, using data from 1600 participants of the Multicenter OA Study (MOST), a large 30-month prospective cohort. We also propose examining the relation of subchondral bone attrition with cartilage defects on MRI, and with knee pain. Thus, this study proposes to examine potential contributors to the development and progression of OA, and identify potential targets for therapeutic strategies. Relevance: OA is the most common form of arthritis with no proven therapies for its management. Given our aging population, this constitutes a major public health concern. If we determine that mechanical and systemic factors interact to produce bony abnormalities in OA, this would suggest that both systemic and mechanical aspects must be targeted to successfully treat OA, including possibly antiresorptive therapy and vitamins D and K supplements in combination with knee braces.