Predictors and Consequences of Subchondral Bone Attrition in Osteoarthritis

描述（由申请人提供）：我是一名流变学家，在大卫博士的指导下进行研究培训。波士顿大学医学院的Felson博士。我还在攻读流行病学博士学位。我近期的职业目标是继续进行临床研究培训，以使自己成为一名独立的研究者。我的长期目标是继续作为一名临床科学家的学术地位，研究生涯集中在风湿性疾病的流行病学研究。目前，我的兴趣在于研究骨关节炎（OA）的病理生理学贡献者，特别是OA中与骨健康相关的因素。 博士Felson和他的研究团队在OA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。在这种研究环境中，我已经开始探索维生素K（一种对骨骼有影响的营养因子）与OA的关系，与这项拟议研究的合作者Sarah Booth博士合作。这项拟议的研究将扩大这种合作，通过关注与OA中软骨下骨磨损相关的因素来研究OA的其他方面，这是一种与大体骨折无关的软骨下骨表面凹陷。软骨下骨被认为在OA的疼痛和进展中起重要作用。软骨下骨的性质改变可能反映了机械和全身因素。我们建议使用多中心OA研究（MOST）的1600名参与者的数据（一个30个月的大型前瞻性队列），检查膝关节MRI上软骨下骨磨损与肢体排列/骨矿物质密度的关系，以及与血液中测量的骨健康相关的营养因素（维生素D和K），以及这些因素的相互作用。我们还建议检查软骨下骨磨损与MRI软骨缺损以及膝关节疼痛的关系。因此，本研究旨在研究OA发生和进展的潜在因素，并确定治疗策略的潜在靶点。 相关性：OA是最常见的关节炎，目前尚无有效的治疗方法。鉴于我们的人口老龄化，这是一个重大的公共卫生问题。如果我们确定机械因素和全身因素相互作用导致骨性关节炎的骨异常，这将表明必须针对全身和机械方面成功治疗骨性关节炎，包括可能的抗吸收治疗和维生素D和K补充剂与膝关节支架的组合。

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.