  Little is known about local and systemic biomarkers in relation to synovitis
and pain in end-stage osteoarthritis (OA) patients. We investigated the
associations between the novel extracellular matrix biomarker, C1M, and local
and systemic interleukin 6 (IL-6) with synovitis and pain. Serum C1M, plasma
and synovial fluid IL-6 (p-IL-6, sf-IL-6) were measured in 104 end-stage knee
OA patients. Contrast-enhanced magnetic resonance imaging (MRI) was used to
semi-quantitatively assess an 11-point synovitis score; pain was assessed by
the Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC) and
the Neuropathic Pain Questionnaire (NPQ). Linear regression was used to
investigate associations between biomarkers and synovitis, and biomarkers and
pain while controlling for age, sex and body mass index. We also tested whether
associations between biomarkers and pain were confounded by synovitis. We found
sf-IL-6 was associated with synovitis in the parapatellar subregion (B=0.006;
95% CI 0.003-0.010), and no association between p-IL-6 and synovitis. We also
observed an association between C1M and synovitis in the peri-ligamentous
subregion (B=0.013; 95% CI 0.003-0.023). Further, sf-IL-6, but not p-IL-6, was
significantly associated with pain, WOMAC (B=0.022; 95% CI 0.004-0.040) and NPQ
(B=0.043;95% CI 0.005-0.082). There was no association between C1M and WOMAC
pain but we did find an association between C1M and NPQ (B=0.229; 95% CI
0.036-0.422). Lastly, synovitis explained both biomarker-NPQ associations, but
not the biomarker-WOMAC association. These results suggest C1M and IL-6 are
associated with synovitis and pain, and synovitis is an important confounding
variable when studying biomarkers and neuropathic features in OA patients.
