06-05-2025
Early Osteoarthritis Needs Better Definition(s)
INCHEON, South Korea — Defining early knee osteoarthritis (OA) as people who do not have symptoms but do have radiographic or MRI changes could offer greater opportunity for interventions to prevent symptomatic or structural decline, a speaker argued at the World Congress on Osteoarthritis (OARSI) 2025 Annual Meeting.
Grace Hsiao-Wei Lo, MD, MS
Rheumatologist and Epidemiologist Grace Hsiao-Wei Lo, MD, MS, an associate professor in the Section of Immunology, Allergy, and Rheumatology at Baylor College of Medicine, Houston, explored how the concepts of early OA and pre-OA could be defined, and what those definitions mean for understanding, research, and prevention of the disease.
'Early osteoarthritis is a term that means a lot in the research community,' Lo said. 'However, there's not a consensus on what this construct should mean.'
That lack of consensus could be impeding the development of disease-modifying OA drugs, if it meant that interventions were being tested in individuals who actually had late disease, not early disease. 'If we change our focus to an earlier part of the natural history of the disease, then we might be more successful,' she said.
However, the challenge is that there are a range of possible definitions for early OA, and it's not clear which ones are mostly predictive of progression to clinical disease, defined as Kellgren and Lawrence (KL) grade 2 or above: Formation of osteophytes, narrowing of the joint cartilage, and sclerosis of the subchondral bone.
Early MRI Changes
In people with KL grade disease of 0 or 1, numerous studies have found pathological evidence of disease on x-ray or MRI, Lo said.
For example, a 2014 MRI study by Leena Sharma and colleagues found that among people who had a KL grade of 0 for both knees, 76% had articular cartilage damage, 61% had bone marrow lesions, and 21% had meniscal tear. Those with more evidence of disease on MRI were more likely to have persistent symptoms of knee OA and cartilage damage. Lo said this indicated that even people without radiographic evidence of disease could have changes on MRI.
'It tells us that we know there are radiographic changes that are typical for osteoarthritis, that there are MRI features of osteoarthritis that can be seen in these without radiographic evidence of disease, that these features are meaningful and that there's no one MRI feature that seemed to be the penultimate predictor for developing KL grade 2,' Lo told the audience.
Another MRI study by Alison H. Chang and colleagues from 2024 took individuals at increased risk of developing symptomatic radiographic knee OA — by virtue of injury, symptoms, family history, or overweight or obesity — and looked at whether MRI evidence at baseline predicted their progression to symptomatic radiographic disease.
'The context here is to look for people who have a particular pathology on MRI, ideally looking for people without symptoms and limitations, and generally we're looking for people with early disease who don't meet the definition of radiographic osteoarthritis,' Lo said.
This study found that some combinations of MRI changes were associated with progression but not everyone with those combinations did progress. 'I would argue that we expect people to go through the different phases of the disease,' Lo said. 'But the hope is that if we can identify people earlier in the natural history, what we're trying to do is stop the progression of disease.'
Radiographic Changes Plus Crepitus
Another phenotype of early disease is in individuals who did have radiographic evidence of disease but without symptoms. Here, Lo cited a study she was involved in, which looked at the predictive value of crepitus in individuals without symptomatic knee OA at baseline.
This study found that patient-reported knee crepitus predicted the development of symptomatic OA, and most of those who went on to symptomatic disease were those with preexisting radiographic evidence of disease. 'This made sense if you believe that people have to have some pathology before they develop symptoms,' Lo said.
Other Early Disease Concepts
Another possible phenotype of early OA is in people without MRI changes, without radiographic changes, and without symptoms, but who have elevated levels of an as-yet unidentified biomarker.
Lo also touched on the idea of pre-OA, and whether it might be possible to find people in whom interventions could prevent symptoms or structural progression. One possible group are those who have experienced anterior cruciate ligament injury, as there was growing evidence they were at elevated risk for knee OA. 'Targeting the people who have had ACL tear is an opportunity to address people who have pre-OA,' she said.
Lo told the audience that these definitions of early OA weren't the only ones out there, but did give an opportunity to potentially enrich clinical trials and observational studies with individuals who were most likely to have outcomes of interest. 'The only way that we can really clarify which definition, or maybe definitions, are the most useful is for us to really systematically evaluate many of them,' she said.
Speaking to Medscape Medical News , Lo said part of the problem is that we don't know what counts as the beginning of OA. 'People pretty uniformly agree that once you have KL2, everybody agrees that that's established disease, but before that there's a lot of disagreement on what counts as a diagnosis of early osteoarthritis,' she said.
But finding individuals with early disease has opened the door to early interventions, she said, pointing to evidence that something as simple as walking might reduce the risk of people progressing to clinical OA.
Commenting on the presentation, Physiotherapist Brooke Patterson, PhD, of La Trobe University in Melbourne, Australia, said there was great interest in defining early OA and pre-OA, particularly for younger individuals with sports-related knee injuries that might increase their risk for OA. 'For these young people that are getting the burden of the disease in their 30s and 40s and then having knee replacements,' it's important for us to talk about it, she said to Medscape Medical News .
