Bending MRI to diagnose joint disease

Magnetic resonance imaging could provide an early diagnosis of osteoarthritis (OA), the most common form of arthritis, according to scientists speaking at the recent meeting of the American Chemical Society.

Osteoarthritis has turned out to be the bane of the Baby Boom generation, causing joint pain and disability for millions of people, more than half of those over the age of 65 in fact. Unfortunately, current approaches to diagnosing the disease cannot provide definitive results until the disease is in the advanced stages. This is often when symptoms have become severe and irreversible joint damage may already have occurred.

Now, chemist Alexej Jerschow and Ravinder Regatte of the School of Medicine at New York University in New York, and their colleagues at Tel Aviv University, Israel, have developed a new approach to OA diagnosis that could provide medical intervention with a much earlier entry point and so potentially reduce or even prevent debilitating and permanent joint damage.

"Our methods have the potential of providing early warning signs for cartilage disorders like osteoarthritis, thus potentially avoiding surgery and physical therapy later on," explains Jerschow, "Also, the effectiveness of early preventative drug therapies can be better assessed with these methods."

Osteoarthritis damages cartilage, the tough, elastic material that cushions moving parts of joints, the knee and hip joints are especially prone to the condition. Indeed, OA is the most common reason for total hip and total knee replacement surgery. Essentially osteoarthritis wears away the cartilage at the ends of bones, this causes bony protrusions, or spurs, to grow from the edge of the bone and leads to an increase in the amount of synovial fluid within the joint. This makes the joint feel stiff and sore. "It has all these painful consequences and makes it difficult to move," says Regatte, "it results in a severe loss of quality of life for those who are affected by it."

The team has now modified MRI to allow them to determine the concentration of the biopolymer glycosaminogycans (GAG) found in cartilage. GAGs are long unbranched carbohydrates essential for human musculoskeletal function, cell regulation, and spinal function.

The researchers have demonstrated that it is possible to exploit GAG's exchangeable protons to directly measure localized GAG concentration in vivo with high sensitivity. "This material holds lots of water and endows cartilage with its tough, elastic properties. GAG is also, however, well-known as a biomarker for both osteoarthritis and degenerative disc disease, a common cause of debilitating back pain. Jerschow points out that a low concentration of GAG in the joints correlates well with the onset of osteoarthritis and other cartilage disorders.

Advanced OA is very easy to diagnose, Regatte says. However, once the disease is in its advanced stages, usually the only option for the patient is joint replacement. With early detection, physicians could prescribe medication, lifestyle or exercise changes. They might even recommend dietary supplements, such as glucosamine combined with chondroitin (itself a GAG), for which there is some inconclusive evidence of benefit.

"Given the lack of knowledge about OA, I think any method that is non-invasive and relatively easy to apply will be quite valuable," adds Jerschow, Not only do you address diagnosis, but you address how we can understand OA's mechanism."

Regatte adds that the test might also be used to improve existing cartilage-boosting drugs by providing a clearer indication as to whether a particular compound is having a measurable, positive effect on reducing cartilage damage. "There are drugs on the market for OA treatment, but no one really knows how effective they are. After having done the research, we got a lot of calls from pharmaceutical companies wanting to show that their drugs work," says Jerschow.

The researchers point out that their variation on the MRI theme costs no more than conventional MRI and takes no longer to run. Diagnosis could be given on a same day basis. "I really hope it will develop into the gold standard technique," Jerschow adds, "I'm pretty confident in saying that its one of the better methods out there for testing cartilage health."

Glycosaminogycans (GAGs) are involved in other functions in the human body. The researchers suggest that mapping GAG concentration could also find application in diagnosis, monitoring, and drug efficacy assessment in various other diseases.

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.