Reduction of the Serum Levels of a Specific Biomarker of Cartilage Degradation (Coll2-1) by Hyaluronic Acid (KARTILAGE® CROSS) Compared to Placebo in Painful Knee Osteoarthritis Patients: the EPIKART Study, a Pilot Prospective Comparative Randomized Double Blind Trial.
This is the first randomized double-blind placebo controlled trial showing that 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.
Effect of chondroitin sulfate on soluble biomarkers of osteoarthritis: a method to analyze and interpret the results from an open-label trial in unilateral knee osteoarthritis patients
This study proposes a new approach for the analysis and the interpretation of the individual variation in biomarker levels and introduces the notion of metabolic responders.
Seventy two patients with unilateral symptomatic knee OA were involved in a post-authorization open-label study evaluating CS (800 mg/day). The primary outcome was the % relative change in serum Coll2-1 (sColl2-1). The secondary outcomes were the evaluation of pain (VAS) and function (Lequesne’s Index). Responders and non-responders were classified according to OMERACT-OARSI recommendations. Finally, an original cut-off method was applied to categorize patients and interpret individual variations in serum levels of Coll2-1.
Review of Soluble Biomarkers of Osteoarthritis: Lessons From Animal Models
The goal of this narrative review is to summarize the scientific data available in the literature on soluble biomarkers in animal models of OA.
A literature search was conducted using the PubMed/ Medline and Scopus databases between February 1995 and December 2015. All original articles, systematic and narrative reviews published in French or in English were considered.
We summarized the data of 69 studies and proposed a classification scheme for OA biomarkers in animal studies, largely inspired by the BIPEDS classification.
Studies about biomarkers and animal models indicate that some markers could be valuable to monitor OA progression and assess therapeutic response in some animal models.
Soluble biomarkers development in osteoarthritis: from discovery to personalized medicine
Specific soluble biomarkers could be a precious tool for diagnosis, prognosis and personalized management of osteoarthritic (OA) patients.
To describe the path of soluble biomarker development from discovery to clinical qualification and regulatory adoption toward OA-related biomarker qualification.
METHODS AND RESULTS:
This review summarizes current guidance on the use of biomarkers in OA in clinical trials and their utility at five stages, including preclinical development and phase 1 to phase 4 trials. It also presents all the available regulatory requirements.
The path through the adoption of a specific soluble biomarker for OA is steep but is worth the challenge due to the benefit that it can provide
Fibulin-3 fragments are prognostic biomarkers of osteoarthritis incidence in overweight and obese women.
To determine the association between three fibulin-3 peptides and the incidence of radiographic and clinical knee osteoarthritis (OA).
Women between 50 and 60 years, with a BMI ≥ 27 kg/m2, free of knee OA, were recruited. Using binary logistic regression, the association between baseline concentration of serum fibulin (Fib)3-1, Fib3-2 and Fib3-3 and incidence of clinical and radiographic knee OA after 30 months of follow-up was evaluated.
Baseline and follow-up measurements were available for 241 women with a mean age of 55.9 ± 3.2 years and mean BMI of 31.7 ± 3.6 kg/m2. None of the concentrations of the three Fib3 epitopes were associated with the incidence of medial or lateral joint space narrowing ≥1.0 mm. or the incidence of K&L grade ≥2 after 30 months. All three Fib3 epitopes were associated with the incidence of the clinical and radiographic ACR-criteria and Fib3-1 and Fib3-3 also with chronic pain at follow-up. When adjusted for the other Fib3 peptide concentrations, only Fib3-1 was significantly associated to the incidence of the ACR criteria (OR 3.2 [1.2-8.7]) and chronic pain at follow-up (OR 3.0 [1.2-7.7]).
Baseline fibulin-3 concentrations are associated with the incidence of clinical knee OA among middle-aged overweight and obese women. Therewith, they meet the criteria of a prognostic biomarker according to the BIPED biomarker classification for OA. Further validation of the fibulin-3 epitopes seems warranted in order to better distinguish subgroups of individuals at increased risk for knee OA development.
Associations of urinary biomarker COLL2-1NO2 with incident clinical and radiographic knee OA in overweight and obese women
To investigate the association between urinary biomarker Coll2-1NO2 (uColl2-1NO2) and incident knee OA after 2.5 years follow-up in middle-aged overweight and obese women at high risk for knee osteoarthritis (OA).
Data were used from PROOF, a randomized controlled trial with 2.5 years follow-up evaluating the preventive effects of a diet and exercise program and oral glucosamine sulphate (double blind and placebo controlled), on development of incident knee OA in women with body mass index ≥ 27 kg/m2 without signs of knee OA at baseline. Baseline and 2.5 years uColl2-1NO2 concentrations were assessed with enzyme-linked immunosorbent assay (ELISA). Primary outcome measure was incidence of knee OA in one or both knees, defined as incidence of either Kellgren & Lawrence grade ≥2, joint space narrowing of ≥1.0 mm or knee OA according to the combined clinical and radiographic ACR-criteria. We used binary logistic regression for the association analyses.
254 women were available for analyses. At 2.5 years follow-up, incident knee OA was present in 72 of 254 women (28.3%). An inversed association was found between baseline uColl2-1NO2 and incident knee OA at 2.5 years (OR 0.74, 95% CI 0.55-0.99). The concentration at 2.5 years and the change in concentration over 2.5 years did not show significant associations with the outcome.
In overweight and obese middle-aged women, not higher but lower baseline uColl2-1NO2 concentration was significantly associated with an increased risk for incident knee OA. This interesting but counterintuitive outcome makes further validation of this biomarker warranted.
Oleuropein or rutin consumption decreases the spontaneous development of osteoarthritis in the Hartley guinea pig
Oleuropein and rutin ± curcumin significantly slowed down the progression of spontaneous OA lesions in guinea pigs. While no additive effect was seen in the curcumin + rutin group, the differential effects of oleuropein and rutin on inflammatory and cartilage catabolic markers suggest an interesting combination for future studies in OA protection.
Histologically, all treatments significantly reduced the cartilage degradation score (P < 0.01), but only oleuropein significantly decreased the synovial histological score (P < 0.05) and serum PGE2 levels (P < 0.01) compared to the control group. Coll2-1 was decreased by rutin and the combination of rutin/curcumin, Fib3-1 and Fib3-2 were only decreased by the rutin/curcumin mixture, while Coll2-1NO2 was significantly decreased by all treatments (P < 0.05).
Decrease of a specific biomarker of collagen degradation in osteoarthritis, Coll2-1, by treatment with highly bioavailable curcumin during an exploratory clinical trial
This study highlighted the potential effect of curcumin in knee OA patient. This effect was reflected by the variation of a cartilage specific biomarker, Coll2-1 that was rapidly affected by the treatment. These results are encouraging for the qualification of Coll2-1 as a biomarker for the evaluation of curcumin in OA treatment.
Early Decrease of Serum Biomarkers of Type II Collagen Degradation (Coll2-1) and Joint Inflammation (Coll2-1 NO2) by Hyaluronic Acid Intra-Articular Injections in Patients With Knee Osteoarthritis:A Research Study Part of the Biovisco Study
To measure the evolution of the serum levels of specific Osteoarthritis (OA) biomarker, Coll2-1 and Coll2-1 NO2 in knee osteoarthritic patients after viscosupplementation (VS). Fifty-one patients with unilateral symptomatic knee were recruited for this prospective open label study. They received three intra-articular injections of 2 ml of hyaluronic acid (Hylan GF-20) and were followed for 3 months. The serum concentrations of Coll2-1 and Coll2-1 NO2 were significantly higher in KL III/IV patients compared to KL I/II patients at baseline and decreased systematically over time after VS.
Collagen catabolism through Coll2-1 and Coll2-1NO2 and myeloperoxidase activity in marathon runners
To determine the influence of marathon on the serum levels of two markers of cartilage degradation, Coll2-1 and its nitrated form, Coll2-1NO2, and of a marker of neutrophils activation, the myeloperoxidase (MPO).
Fibulin 3 Peptides Fib3-1 and Fib3-2 Are Potential Biomarkers of Osteoarthritis
Thirteen proteins within spots that were significantly modified between groups were identified. Two peptides of fibulin 3, named Fib3-1 and Fib3-2, were of particular interest. Using area under the receiver operating characteristic curve analysis, we demonstrated that Fib3-1 and Fib3-2 levels discriminate between OA and normal populations.
Collagen fibril disruption occurs early in primary guinea pig knee osteoarthritis, only serum Coll2-1 increased
Collagen fibril disruption and expression of the collagenase-generated cleavage neoepitope, 9A4, were observed as early as 2 months of age, despite the appearance of histological OA at 4 months of age. Only serum Coll2-1 increased coincident with the early disruption of the collagen fibril between 3 weeks and 7 months.