Biological markers in osteoarthritis

Rousseau, Jean-Charles; Garnero, Patrick

doi:10.1016/j.bone.2012.04.001

Cited by 136 publications

(93 citation statements)

References 146 publications

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“…Such markers of osteoarthritis could facilitate early diagnosis of joint destruction, disease prognosis and progression monitoring, which could be detectable with an early biochemical test 13 . Over the years, a series of markers have been proposed that may reflect the synthesis or degradation of the joint tissues.…”

Section: Introductionmentioning

confidence: 99%

Discovery of circulating proteins associated to knee radiographic osteoarthritis

Lourido

Ayoglu

Fernández‐Tajes

et al. 2017

Sci Rep

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Currently there are no sufficiently sensitive biomarkers able to reflect changes in joint remodelling during osteoarthritis (OA). In this work, we took an affinity proteomic approach to profile serum samples for proteins that could serve as indicators for the diagnosis of radiographic knee OA. Antibody suspension bead arrays were applied to analyze serum samples from patients with OA (n = 273), control subjects (n = 76) and patients with rheumatoid arthritis (RA, n = 244). For verification, a focused bead array was built and applied to an independent set of serum samples from patients with OA (n = 188), control individuals (n = 83) and RA (n = 168) patients. A linear regression analysis adjusting for sex, age and body mass index (BMI) revealed that three proteins were significantly elevated (P < 0.05) in serum from OA patients compared to controls: C3, ITIH1 and S100A6. A panel consisting of these three proteins had an area under the curve of 0.82 for the classification of OA and control samples. Moreover, C3 and ITIH1 levels were also found to be significantly elevated (P < 0.05) in OA patients compared to RA patients. Upon validation in additional study sets, the alterations of these three candidate serum biomarker proteins could support the diagnosis of radiographic knee OA.

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Section: Introductionmentioning

confidence: 99%

Discovery of circulating proteins associated to knee radiographic osteoarthritis

Lourido

Ayoglu

Fernández‐Tajes

et al. 2017

Sci Rep

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“…Several soluble biomarkers have been identified as potential candidates to predict or monitor the efficacy of intervention in OA [13]. Among them, type II collagen derivatives have been extensively investigated [14–17].…”

Section: Introductionmentioning

confidence: 99%

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

Henrotin

Bérenbaum

Chevalier³

et al. 2017

BMC Musculoskelet Disord

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BackgroundViscosupplementation is a symptomatic treatment of the knee osteoarthritis based on the intra-articular injection of hyaluronic acid (IAHA). Although many studies have investigated its effect on symptoms, few clinical studies have focused on its effects on biologicals markers of cartilage metabolism. In this study, we assessed the effect of an intra-articular injection of a reticulated hyaluronic acid compound on the level of a specific biomarker of type II collagen degradation.MethodsEighty one patients with symptomatic knee osteoarthritis were included in this randomized placebo controlled trial testing a reticulated hyaluronic acid (HA) with mannitol (KARTILAGE® CROSS, 16 mg/ml, one single injection of 2.2 mL; IAHA) versus saline solution. 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, 3 months after injection). Secondary outcomes concerned clinical evaluation and tolerance to the study product.ResultsA significant effect of IAHA 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%; P = 0.01). The same significant difference was observed between groups in the per protocol population (57.1% vs 29.0%; P = 0.02) 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. No significant differences between groups were observed on the changes in function (Lequesne index) or pain and on the number of adverse events.ConclusionsThis 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. This finding suggests that IAHA 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.Trial registration NCT02951585; clinicaltrial.gov. Retrospectively registered on October 28, 2016.

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“…Non-collagenous proteins like complex oligomeric matrix protein (COMP), released into the SF during HAC degradation [26], may also indicate an increase matrix turn-over in the HAC in response to exercise [27, 28], making difficult to discriminate between normal and OA-affected patients. In most cases a substantial overlap with controls indicates that a single biomarker alone may have limited diagnostic potential [29], preferring the combination of different biomarkers for assessing disease activity on the individual level [30, 31]. Practical application of biomarkers assessment was found very promising in racehorses, where they could indicate the pattern of disease activity (inflammatory versus degradative status of the joint) during PTOA and verifying treatments efficacy like in other animal models [32], but they continue to be of limited use due to the insufficiency of longitudinal studies.…”

Section: Introductionmentioning

confidence: 99%

Pro-inflammatory cytokines and structural biomarkers are effective to categorize osteoarthritis phenotype and progression in Standardbred racehorses over five years of racing career

et al. 2016

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BackgroundJoint impact injuries initiate a progressive articular damage finally leading to post-traumatic osteoarthritis (PTOA). Racehorses represent an ideal, naturally available, animal model of the disease. Standardbred racehorses developing traumatic osteoarthritis of the fetlock joint during the first year of their career were enrolled in our study. Age-matched controls were contemporarily included. Biomarker levels of equine osteoarthritis were measured in serum and synovial fluid (SF) at baseline, and repeated yearly over the next 4 years of training (from T1 to T4). The effect of time and disease on the biomarker concentrations were analysed, and their relationship with clinical and radiographic parameters were assessed. We hypothesized that the kinetics of pro-inflammatory cytokines and structural biomarkers of joint disease would demonstrate progression of degenerative joint status during post-traumatic osteoarthritis and clarify the effect of early joint trauma.ResultsThe concentrations of IL1-ß, IL-6, TNF-α in the SF of PTOA group peaked at T0, decreased at T1, and then progressively increased with time, reaching levels higher than those observed at baseline starting from T3. CTXII and COMP levels were similar in PTOA and control horses at baseline, and increased in serum and synovial fluid of PTOA horses starting from T2 (serum and synovial CTXII, and serum COMP) or T3 (synovial COMP). The percentual change of TNF-α in the SF of the affected joints independently contributed to explaining the radiological changes at T3 vs T2 and T4 vs T3.Conclusions Temporal changes of selected biomarkers in STBRs with an acute episode of traumatic fetlock OA demonstrated that long-term increased concentrations of inflammatory cytokines, type II collagen fragments and COMP, in the SF and serum, are related to PTOA. Based on the observed decrease in inflammatory merkers at T1, we hypothesize that the progression of PTOA could be effectively modulated by proper treatment strategies. Annual variations of synovial concentration of TNF-α can reliably predict radiographic progression of PTOA.

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Biological markers in osteoarthritis

Cited by 136 publications

References 146 publications

Discovery of circulating proteins associated to knee radiographic osteoarthritis

Discovery of circulating proteins associated to knee radiographic osteoarthritis

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

Pro-inflammatory cytokines and structural biomarkers are effective to categorize osteoarthritis phenotype and progression in Standardbred racehorses over five years of racing career

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