Osteoarthritis is a leading cause of disability worldwide, affecting most people at some point in their lives. It causes pain and joint stiffness in knees, hips, hands, feet, or spine due to degeneration of joint tissues, including bone, cartilage, tendons, and ligaments. While the causes and progression of osteoarthritis remain poorly understood, injuries, such as trauma, ligament tears, fractures, or repetitive stress, are known risk factors for development of OA.
Current treatment options for osteoarthritis remain limited. This is largely due to a lack of non-invasive tools that can detect early and reversible joint changes. Research is focused on discovering markers that can identify the disease in its early stages and developing disease-modifying therapies. A Stanford University team is studying increased bone remodeling, a process where new bone tissue forms in place of old or damaged bone, as an early marker of bone degeneration. Bone remodeling could also have an impact on early changes in cartilage tissue structure, and a better understanding of this relationship could lead to development of disease-modifying therapies and interventions.
In their study, published April 12, 2018 in the online edition of Osteoarthritis and Cartilage, the researchers performed simultaneous magnetic resonance imaging (MRI), which can provide high-resolution images with multiple contrasts, and positron-emission tomography (PET), which can image molecular and physiologic changes using a positron-emitting tracer.
Using dual PET and MRI technology, the researchers were able to detect increased bone remodeling in the injured knees of patients likely to get osteoarthritis. This increased bone activity was often seen next to areas of early cartilage tissue degradation, suggesting an important link between degenerative changes in neighboring tissues in the disease.
According to the researchers, this work presents the first technique to simultaneously assess multiple early metabolic and cellular markers of joint tissue health in a population at risk for development of early knee osteoarthritis. With clinical application in mind, they hope to apply this new technology as a diagnostic companion for the development and evaluation of new bone-targeting therapies.
“This exciting study has demonstrated the potential of the advanced multi-modality imaging technology on providing critical information on bone degeneration non-invasively at an early stage,” said Guoying Liu, Ph.D., director of the NIBIB Program in Magnetic Resonance Imaging and Spectroscopy. “We are hopeful that such technology could lead to more accurate diagnosis and assessment of therapy, ultimately reducing overall health care costs due to osteoarthritis.”
For their study, the researchers scanned both knees of 15 participants with a surgically repaired anterior cruciate ligament (ACL) tear in one knee and a healthy, unaffected knee. They then compared bone remodeling in the injured and non-injured knee scans.
Bone is the only tissue in the knee joint with a large blood supply and is able to rapidly change itself when subjected to stress or injury. However, the role of bone injury and bone remodeling is often neglected or studied in the context of structural changes that occur late in the disease processes. Current methods to assess bone remodeling require a biopsy, which is costly and painful. Blood and urine markers can be used, but they are not sufficient to identify early onset of osteoarthritis.
The PET scan provides a new method to study metabolic bone activity, particularly in the thin layer of bone just below the cartilage, called subchondral bone, which is difficult to visualize with other imaging methods. The image is enhanced by a chemical tracer—an injected solution of labeled sodium fluoride—that gets absorbed in areas with high bone remodeling and not by surrounding tissue. The PET images thus offer a new way to study abnormal bone processes that occur after injury that lead to osteoarthritis.
Additionally, MRI can detect early degenerative changes in cartilage tissue structure that occur before actual loss of cartilage tissue. Together, the two imaging modalities provide a unique way to detect multiple, early and reversible signs of the disease, as well as to evaluate how the changes impact neighboring tissues that was not possible with previous methods.
The work was funded in part by NIBIB (EB002524 and K99EB022634) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR0063643 and K24AR062068), both parts of NIH.
Kogan F, Fan A P, Monu U, Iagaru A, Hargreaves B A, Gold G E. Quantitative imaging of bone–cartilage interactions in ACL-injured patients with PET–MRI. Osteoarthritis and Cartilage. June 2018.