Recent years have seen an influx of new treatments for arthritis, with a number of drugs slowing or even stopping the progression of some forms of the disease. Yet treatment for the most common form of arthritis, osteoarthritis, is still limited to easing its symptoms. The problem, in part, is the difficulty in measuring disease progression and determining if a treatment is making an impact on it. X-rays, which show narrowed joint space due to cartilage loss, are often used to monitor disease progression; however, they cannot show small changes in the joint, so it may take one to three years for joint deterioration to be detected. A new development by researchers supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) has the potential to one day change that.
By combining a technique called microcomputed tomography (microCT) - which yields high-resolution, three-dimensional x-ray images - with an x-ray-absorbing contrast agent, researchers at the Georgia Institute of Technology in Atlanta have been able to image the distribution of molecules called proteoglycans in the laboratory. The molecules are critical to the proper functioning of cartilage.
"By detecting proteoglycan content and distribution, the technique reveals information about both the thickness and composition of cartilage," says Marc Levenston, Ph.D., associate professor in Georgia Tech's George W. Woodruff School of Mechanical Engineering. "Both of these are important factors for monitoring the progression and treatment of osteoarthritis."
Levenston and his colleagues first used the technique in vitro to monitor the breakdown of bovine cartilage samples and then to visualize the thin layer of cartilage in a rabbit knee. The next step of the research, which is being funded by a two-year grant from NIAMS, will be to study the use of the technique to nondestructively examine the cartilage of rat knee joints and then attempt to evaluate osteoarthritis progression and monitor cartilage changes in the same live rats over time.
The researchers don't know yet if the technique would be successful in people. "At this point, we are really focusing on developing it as a research tool for preclinical studies on small animals," says Levenston. "We feel that we may be able to provide a lot of additional information about disease progression, especially in the early stages, that can't currently be obtained."
The hope is that their research will lead to ways to monitor cartilage changes with good resolution and little or no invasion of the tissue, and that eventually the technique will allow pharmaceutical researchers to obtain more detailed information about the effects of new drugs and other treatment strategies for osteoarthritis, Levenston says.
In addition to NIAMS, funding for the research was provided by the Arthritis Foundation and National Science Foundation.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS Web site at http://www.niams.nih.gov.
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Palmer AW, Guldberg RE, Levenston ME, Analysis of cartilage matrix fixed charge density and three-dimensional morphology via contrast-enhanced microcomputed tomography. PNAS 2006:103(51):19255-19260.