‘Disturbance and breakdown’ of cartilage holds clues to biomarkers in osteoarthritis
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Understanding the “disturbance and breakdown” of cartilage is critical to finding and using biomarkers in osteoarthritis, according to the keynote speaker at the 2022 OARSI World Congress.
“Maybe I am preaching to the choir here, but there is a medical need for biomarkers in OA,” Christian Thudium, PhD, MSc, of the department of rheumatology at Nordic Bioscience, in Denmark, told attendees.
Although clinical trials have demonstrated the efficacy of some biomarkers, researchers have yet to establish how certain biomarkers can yield symptomatic benefit. Further complicating the matter is the fact that there is significant heterogeneity in OA patient populations.
Another critical point pertains to the nature of OA itself.
“Osteoarthritis is really a tissue turnover disease,” Thudium said.
Digging deeper, Thudium suggested that despite the heterogeneity among this population, all patients with OA demonstrate changes to the extra cellular matrix tissue remodeling. “OA is a disease that is characterized by changes to this matrix,” he said. “It is a balance between the disturbance and the breakdown of tissue.”
Biomarkers that have been explored as part of this cycle of cartilage degradation and formation include PRO-C2, C2M, CTX-II and T2CM, while CTX-I, C3M and osteocalcin are markers of connective tissue sclerosis and thickening.
“Biomarker development has been quite focused on the cartilage,” Thudium said.
These various biomarkers reflect different processes and different velocities of process.
Taking a closer look at specific potential biomarker targets, Thudium described aggrecan and type II collagen as the “building blocks of cartilage.”
“Lower type II collagen and PRO-C2 are associated with progression of OA disease,” he added.
There are also quality of life implications to this observation, according to Thudium. “Tissue turnover in these patients really matters for how they perceive the pain,” he said.
Understanding how cartilage can break down is critical to understanding and predicting disease progression, Thudium added.
“High cartilage degradation is associated with radiographic disease and symptoms,” he said. “A disturbed balance between degradation and formation is associated with increased risk for symptomatic and radiographic disease progression.”
Turning back to the extra cellular matrix, Thudium said that these metabolites are another predictor of both changes in joint structure and predictive of disease progression. He added that the clinical implications of this observation are clear.
“They may identify endotypes more likely to respond to treatment and/or less likely to respond to placebo,” Thudium said. “Systemic markers of synovial tissue turnover are markers of synovial inflammation and associated with aspects of pain and incidence of [knee OA].”
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Thudium C. Markers of synovial inflammation matrix turnover and symptoms. Presented at: OARSI 2022 World Congress on Osteoarthritis; April 7-10; Berlin, Germany (virtual meeting).
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