Specific Biomarker Assessed for Cartilage Degradation

Osteoarthritis (OA) is one of the most common forms of musculoskeletal disorders and one of the major causes of pain and disability in the adult population. Viscosupplementation is a symptomatic treatment of the knee osteoarthritis based on the intra-articular injection of hyaluronic acid (IAHA).

Several soluble biomarkers have been identified as potential candidates to predict or monitor the efficacy of intervention in OA. Type II collagen derivatives have been extensively investigated and Coll2-1, a degradation product of type II collagen, has been found in high concentrations in the synovial fluid of human patients with OA compared with healthy controls.

Scientists at the University Hospital of Liège (Liège, Belgium) and their French colleagues included 81 patients with symptomatic knee osteoarthritis in a randomized placebo controlled trial testing a reticulated hyaluronic acid (HA) with mannitol versus saline. The primary outcome was the percentage of patients with a reduction of at least 10 nmol/L of serum Coll2-1 between baseline and day 90 (D90, three months after injection).

Blood samples were collected and Coll2-1 was determined in patients’ sera using enzyme-linked immunosorbent assay (ELISA) kits. This assay is a competitive immunoassay utilizing a synthetic peptide pre-coated onto the ELISA plate for the quantification of the corresponding antigen in serum samples. The antibody-antigen complex is detected by a chromogenic reaction with 3,3’,5,5’-tetramethylbenzidine (TMB). The reaction is stopped by adding acid to give a colorimetric endpoint that is subsequently determined spectrophotometrically. The limits of quantification for the assay ranged from 31.25 nM to 2,000 nM.

The scientists found that a significant effect of the injection was revealed by the sensitivity analysis of the decrease in cartilage marker. In the intention-to-treat population, the percentage of patients showing a decrease in the levels of serum Coll2-1 between inclusion and D90 showed was higher in HA (56.8%) than in placebo group (28.6%). The same significant difference was observed between groups in the per protocol population: 57.1% versus 29.0%; corresponding to all patients having received the intra-articular injection (IA), being evaluated for the primary outcome on D-10 and D90, and with no major defined deviation.

The authors concluded that an IA injection of reticulated HA with mannitol in knee osteoarthritis patients can reduce the serum levels of Coll2-1, a marker specific of type II collagen degradation. This finding suggests that the specific injection may have a beneficial effect on cartilage degradation and that Coll2-1 could be used for the assessment of a single intra-articular treatment in clinical trials. The study was published on May 26, 2017, in the journal BMC Musculoskeletal Disorders.

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University Hospital of Liège