Traditionally thought to be the result of a suite of issues, the world's most common type of arthritis – osteoarthritis (OA) – actually has a single core driver. These findings, in the largest study of patients with knee OA, has the potential to make drug trials and treatment more targeted and effective.
Researchers at the University of Oxford's Kennedy Institute of Rheumatology (KIR), as part of the the international STEpUP OA (Synovial fluid To detect Endotypes by Unbiased Proteomics in OA) project, analyzed synovial fluid – the lubrication in the knee joint – from more than 1,300 patients with OA, with each sample containing more than 7,000 proteins.
Comparing molecular patterns in these complex samples, the researchers were able to determine that OA has a single fingerprint, however, the biology has some variation due to known risk factors such as age, biological sex and body mass index (BMI).
"This work provides a clear map of the molecular landscape of OA and offers a valuable resource for researchers and pharmaceutical companies," says Dr Thomas Perry, KIR senior post doctoral molecular epidemiologist and first author of the study. "It will allow us to match patients to therapies much more precisely – a crucial step toward developing long-awaited treatments that slow or halt disease progression."
Obese patients, for example, had additional inflammatory signals, but the condition wasn't caused by immune-cell-driven inflammation like what's seen in cases of rheumatoid arthritis. The researchers say, based on their analysis, knee OA in people with obesity appears to be the result of mechanical stress.
This could explain why some people with knee OA progress faster than others in treatment, and such examples could help scientists design better, more targeted clinical trials.
As of now, OA has no approved disease-modifying therapies.
"For decades, the field has debated whether OA is really a group of separate diseases, perhaps explaining why so many clinical trials have failed," says Professor Tonia Vincent, lead investigator and Director of the Arthritis UK Centre for OA Pathogenesis at the KIR. "We revealed no evidence of distinct disease subtypes, instead, we've demonstrated that at the molecular level OA is a single disease with a common set of 'core' pathways, mostly related to tissue injury and repair."
The researchers were only able to make these new findings by using the comprehensive STEpUP OA dataset, which is freely available for scientists to use for study.
Ultimately, the team found that OA is a single disease with clear biological pathways, rather than a blur of subtypes contributing to the chronic condition. And it underpins the importance of treating lifestyle influences that can exacerbate pain and discomfort.
"Understanding the biology of osteoarthritis will help us develop better, more personalized treatments for people with osteoarthritis," says Professor Lucy Donaldson, Director of Research at Arthritis UK. "People experience OA differently – we know for example that peri-menopausal women face higher risk, and that some people see their symptoms progress far more quickly than others.
"Understanding the mechanisms of OA is a crucial step towards understanding why the condition varies so much between individuals," she adds.
The breakthrough work now means researchers have a clear, singular target for better tackling OA.
"It means we can focus on therapies that address this core pathway and adapt them for people with different risk factors," says Vincent. "This is a major step towards development of effective treatments."
The research was published in Nature Communications.
Source: University of Oxford
