Predictors and Consequences of Subchondral Bone Attrition in Osteoarthritis

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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.