Researchers at the University of Arizona Arthritis Center at the UA College of Medicine – Tucson are working to identify treatments to slow the progression of osteoarthritis (OA), supported by a recent $6.1 million, five-year grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health.
The most common cause of disability in the aging population, OA is a complex condition involving not only the breakdown of cartilage in joints but also changes in adjacent soft tissue and bone beneath the cartilage, leading to debilitating joint pain and stiffness and often pain in surrounding muscles and ligaments. The public health impact of knee OA, in particular, is expected to increase dramatically. No cure exists and no FDA-approved drugs are available to prevent development or halt the progression of the condition.
The study, “Risk of Incident Knee OA & Clinical Outcomes Based on Imaging Biomarkers,” builds on two ongoing studies, the Osteoarthritis Initiative (OAI) and the Pivotal OAI MRI Analyses (POMA), an ancillary proposal to the OAI. The OAI was designed to address the lack of biomarkers (biologic features that can be used to measure the presence or progress of a disease or the effects of treatment) for the development and progression of knee OA. The POMA utilized the OAI MRIs (magnetic resonance imaging) to identify imaging biomarkers of knee OA development and progression as long as 48 months prior to the onset of radiographic knee OA (ROA).
ROA symptoms may not correlate with joint damage shown by X-ray or MRI. People with ROA may have little or no pain, yet joint function still may be significantly impacted, causing difficulty performing activities of daily living.
“Recent advances in magnetic resonance imaging have improved our understanding of the relationship between pathology and the structural changes to cartilage, subchondral bone and the surrounding soft tissues of the joint in OA,” said study Principal Investigator C. Kent Kwoh, MD. An internationally recognized expert in osteoarthritis, rheumatoid arthritis and other joint diseases, Dr. Kwoh is director of the University of Arizona Arthritis Center; professor of medicine and medical imaging at the UA College of Medicine – Tucson; the Charles A.L. and Suzanne M. Stephens Chair of Rheumatology; and chief of the Division of Rheumatology, UA Department of Medicine.
“The overall objective of this proposal is to take advantage of a time-limited opportunity to build on our prior work and leverage the wealth of longitudinal data, including high-resolution MRI imaging at 3 Tesla, which already has been accumulated in the OAI,” Dr. Kwoh continued. “We will be able test whether structural changes detectable by MRI predict the onset of ROA and the development of important clinical outcomes 24 months to 120 months later, and therefore much earlier in the disease course than currently established. A 120-month visit will be added to the OAI for participants with knees that did not have ROA at baseline.”
The 3T MRI data is a critical feature of the study. MRI—magnetic resonance imaging—scanners come in different magnetic field strengths measured in Teslas, or “T.” A 3T MRI is stronger than a usual MRI used for clinical care and provides extremely sharp images with minute details to better visualize joint structures.
“The specific aims of this study are to identify imaging biomarkers of the development of incident ROA earlier in the disease course – and to identify the association of imaging biomarkers with changes in pain, function and performance associated with the onset of ROA,” said study Co-PI Ali Guermazi, MD, PhD, professor of radiology, section chief of musculoskeletal imaging and director of the Quantitative Imaging Center at Boston University School of Medicine. Noted for his contributions in the diagnosis and disease progression assessment of osteoarthritis using MRI, Dr. Guermazi’s work focuses on identifying structural risk factors for developing and worsening osteoarthritis. He has been involved in developing several radiological methods to assess osteoarthritis disease risk and progression, and has been involved as an MRI reader in several large NIH-funded studies, including the OAI.
Dr. Kwoh said, “Ultimately, this line of research will help to identify key risk factors for the development of OA and OA structural disease progression, and to identify potential targets for preventative and/or therapeutic interventions.”
Study collaborators include researchers with four OAI clinical centers: University of Pittsburgh, University of Maryland, Ohio State University and Memorial Hospital of Rhode Island, as well as with Northwestern University and Boston University. The University of San Francisco is providing data management.
This research is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH under Award Number R01AR066601. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.