A new study by the Boston University School of Medicine and the University of Erlangen-Nuremberg has detected structural changes in the knee joint that precede signs of osteoarthritis seen in X-rays. The study, which was supported in part by the NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), calls into question the assumption that damage to cartilage is the primary underlying cause of osteoarthritis. The findings appeared in the journal Arthritis and Rheumatology.

For decades, it has been understood that osteoarthritis stems primarily from wear and tear on the cartilage in the joint. Osteoarthritis is often diagnosed using characteristics visible on X-rays, such as narrowing of the joint space, which occurs as the cartilage breaks down, and development of bone spurs, which can form at the edges of the joint.

The team of scientists found that MRI reveal early changes to the joint that can predict the development of knee osteoarthritis, which challenges the widely held believe that damage to cartilage along initiates the disease.

Studies using magnetic resonance imaging  (MRI), a technology that enables researchers to visualize all the joint’s tissues, have revealed that changes throughout the joint are associated with osteoarthritis. These findings suggested that factors other than loss of cartilage may contribute to disease onset.

In this study, a team led by Frank W. Roemer, M.D., of the Boston University School of Medicine and the University of Erlangen-Nuremberg, set out to assess if structural features detectable by MRI can predict the changes seen on X-rays. If so, the MRI findings could help identify people at risk of joint degeneration. They may also yield insights into the early stages of the disease and guide research on therapies to slow or stop its onset.

The research had nearly 5,000 participants, ranged in age from 45 – 79 when they joined the study. MRI and X-ray knee images were taken at the first visit, and again yearly for four years. The team  led by Dr Frank W Roemer also used data from the US National Institute of Health observational study of knee osteoarthritis occurrence and progression.

The researchers compared the MRI images of 355 “case knees”—knees that developed osteoarthritis within the four-year period, as determined by characteristic signs seen on X-rays – to 355 matched control knees. They found that two years prior to the development of radiographic knee osteoarthritis, the case knees were more likely to have shown signs of inflammation and damage to the medial meniscus, a crescent-shaped segment of cartilage on the inner side of the knee joint.

Inflammation and lesions in the bone marrow of the leg bones that border the joint were the most prominent predictors of the development of radiographic osteoarthritis one year later in the study. Conversely, cartilage damage did not strongly correlate with the occurrence of radiographic knee osteoarthritis one to two years later, suggesting that cartilage breakdown plays a lesser or later role in the development of the disease than previously believed.

The study showed patients with more abnormalities seen by MRI were more likely to develop radiographic osteoarthritis later on. The study showed that five or six structural knee abnormalities brought a six-fold increased risk of developing the disease two years later, compared to having one or no MRI-observable structural defects.

Together, the findings suggest that cartilage damage may not be central to the development of osteoarthritis. Clinicians should consider a more nuanced view in which multiple factors are at play, setting the stage for the disease many months earlier than previously assumed, according to the researchers.

Dr Roemer says, “For many years, much of the research on therapies for osteoarthritis has focused on preserving the dignity of joint cartilage. Our work has provided a more detailed picture of how we view the events leading up to osteoarthritis, and has uncovered risk factors that will help us understand how the disease develops. Hopefully, it will lead to novel therapeutic targets.”

There is often a tingle of excitement when a new medical breakthrough or successful research trial is announced. Unfortunately this can be followed by an opposing sense of disappointment, when it appears not to apply to us or to be relevant only in the future. Still, progress is progress and the spin offs may have benefits for many.

As these researchers say, until recently osteoarthritis was considered to be simply ‘wear and tear’ on our joints, without quantifying the stresses on a particular joint and the resulting damage, which varies from person to person, even from joint to joint in the same individual. Now we can explain this through biomechanics, that these stresses are far more subtle, often far less severe than originally thought but applied over a long period of time still potentially very damaging.

This study adds a new dimension, suggesting there are other factors including perhaps genetic predispositions that may influence those particularly at risk. It also highlights damage to the meniscus, what we tend to call incorrectly the cartilage of the knee joint. Not that it isn’t cartilage, but of course is not the only one.

What can we learn from this? Firstly that, even with a condition considered not long ago too be a straightforward mechanical problem it is always worth re-examining and never taking for granted. And as they conclude, when other underlying causes are identified so the prospect of new and novel therapies emerges. We have seen this with the understanding of biomechanics, applied to those with already established disease. Never dismiss anything as irrelevant, because that so often changes.