Serum concentrations of cartilage oligomeric matrix protein and bone sialoprotein in hip osteoarthritis: A one year prospective study

Conrozier, Thierry; Saxne, Tore; Fan, Charles Shan Sei; Mathieu, Pierre; Tron, Anne-Marie; Heinegård, Dick; Vignon, E.

doi:10.1136/ard.57.9.527

Cited by 92 publications

(80 citation statements)

References 30 publications

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“…Predictive values of serum levels of C-reactive protein (43), COMP (44,45), and hyaluronic acid (46) have been found in some studies, but not in all (47). However, molecular markers investigated in these studies were not specific to joint tissue (6), and none of the studies evaluated the metabolism of type II collagen, the most abundant protein of cartilage matrix.…”

Section: Discussionmentioning

confidence: 99%

Uncoupling of type II collagen synthesis and degradation predicts progression of joint damage in patients with knee osteoarthritis

Garnero¹,

Ayral²,

Rousseau³

et al. 2002

Arthritis & Rheumatism

264

200

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Objective. The hallmark of osteoarthritis (OA) is the loss of articular cartilage. This loss arises from an imbalance between cartilage synthesis and cartilage degradation over a variable period of time. The aims of this study were to investigate the rates of these processes in patients with knee OA using two new molecular markers and to investigate whether the combined use of these markers could predict the progression of joint damage evaluated by both radiography and arthroscopy of the joints during a period of 1 year.Methods. Seventy-five patients with medial knee OA (51 women, 24 men; mean ؎ SD age 63 ؎ 8 years, mean ؎ SD disease duration 4.8 ؎ 5.2 years) were studied prospectively. At baseline, we measured serum levels of N-propeptide of type IIA procollagen (PIIANP) and urinary excretion of C-terminal crosslinking telopeptide of type II collagen (CTX-II) as markers of type II collagen synthesis and degradation, respectively. Joint space width (JSW) on radiography and medial chondropathy at arthroscopy (assessed using a 100-mm visual analog scale [VAS]) were measured in all patients at baseline and in 52 patients at 1 year. Progression of joint destruction was defined as a decrease of >0.5 mm in JSW on radiography and as increased chondropathy (an increase in the VAS score of >8.0 units) between the baseline and 1-year evaluations.Results. At baseline, compared with 58 healthy age-and sex-matched controls, patients with knee OA had decreased serum levels of PIIANP (20 ng/ml versus 29 ng/ml; P < 0.001) and increased urinary excretion of CTX-II (618 ng/mmole creatinine [Cr] versus 367 ng/ mmole Cr; P < 0.001). The highest discrimination between OA patients and controls was obtained by combining PIIANP and CTX-II in an uncoupling index (Z score CTX-II ؊ Z score PIIANP), which yielded a mean Z score of 2.9 (P < 0.0001). Increased baseline values in the uncoupling index were associated with greater progression of joint damage evaluated either by changes in JSW (r ‫؍‬ ؊0.46, P ‫؍‬ 0.0016) or by VAS score (r ‫؍‬ 0.36, P ‫؍‬ 0.014). Patients with both low levels of PIIANP (less than or equal to the mean ؊ 1 SD in controls) and high levels of CTX-II (greater than or equal to the mean ؉ 1 SD in controls) had an 8-fold more rapid progression of joint damage than other patients (P ‫؍‬ 0.012 and P < 0.0001 as assessed by radiography and arthroscopy, respectively) and had relative risks of progression of 2.9 (95% confidence interval [95% CI] 0.80-11.1) and 9.3 (95% CI 2.2-39) by radiography and arthroscopy, respectively.Conclusion. Patients with knee OA are characterized by an uncoupling of type II collagen synthesis and degradation which can be detected by assays for serum PIIANP and urinary CTX-II. The combination of these two new markers could be useful for identifying knee OA patients at high risk for rapid progression of joint damage.

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Section: Discussionmentioning

confidence: 99%

Uncoupling of type II collagen synthesis and degradation predicts progression of joint damage in patients with knee osteoarthritis

Garnero¹,

Ayral²,

Rousseau³

et al. 2002

Arthritis & Rheumatism

264

200

View full text Add to dashboard Cite

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“…Serum CRP levels were greater with more severe hip OA (1.3-2.9 times greater, effect size d = 1.2-1.8) than those with less severe OA. Increased levels of cartilage oligomeric protein (COMP) were associated with increasing hip OA severity in one study (effect size d = 4.9) [15] but not in three other studies [6,14,20]. However, a recent study [6] demonstrated increased levels of deamidated COMP (DCOMP) to be associated with increasing hip OA severity as measured by the Kellgren-Lawrence grade, whereas COMP demonstrated no association.…”

Section: Disease Stagingmentioning

confidence: 93%

“…Control [1,5,12,18,19,49]; atrophic versus hypertrophic in two studies [13,14]; and radiographic OA classification in five studies [6,23,42,47,48]. Two studies [15,20] analyzed minimum joint space width as a continuous variable relative to biomarker levels. Eleven ''progression'' studies [7-9, 15, 17, 24, 29, 30, 35, 37, 39] investigated the association of 13 different biomarker levels with the progression of hip OA.…”

Section: Literature Searchmentioning

confidence: 99%

“…Eleven ''progression'' studies [7-9, 15, 17, 24, 29, 30, 35, 37, 39] investigated the association of 13 different biomarker levels with the progression of hip OA. Of the 11 studies, four looked at progression of known hip OA [9,15,37,39]; three studies investigated the progression to incident hip OA from unspecified prearthritic hip disease [8,17,29]; and four studies investigated both OA progression and incidence [7,24,30,35]. Duration of followup to evaluate OA progression ranged from 1 year to 15 years.…”

Section: Literature Searchmentioning

confidence: 99%

“…Six different biomarkers were associated with hip OA progression (Table 4), including elevations in COMP (three studies [7,15,24]) and decreases in 25-OH Vitamin D (two studies [8,29]). However, all COMP studies demonstrated relatively small effect sizes (d \ 0.3).…”

Section: Prognosismentioning

confidence: 99%

See 2 more Smart Citations

What Is the Utility of Biomarkers for Assessing the Pathophysiology of Hip Osteoarthritis? A Systematic Review

Nepple

Thomason

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Serum cartilage oligomeric matrix protein reflects osteoarthritis presence and severity: The Johnston county osteoarthritis project

Clark

Jordan

Vilı́m

et al. 1999

Arthritis & Rheumatism

235

150

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Objective. To characterize serum cartilage oligomeric matrix protein (COMP) levels by age and gender for a radiographically defined population free of hip and knee osteoarthritis (OA), and to examine the potential utility of COMP as a diagnostic biomarker for knee OA.Methods. Serum samples and knee and hip radiographs were obtained at a baseline evaluation as part of the Johnston County Osteoarthritis Project, a population-based study of OA in rural North Carolina. A total of 291 Caucasian participants were randomly selected for COMP analysis, 143 patients with radiographic knee OA (Kellgren/Lawrence [K/L] grade >2) and 148 controls with neither hip nor knee OA (K/L grade 0), evenly distributed by age and gender. COMP was quantified by competitive enzyme-linked immunosorbent assay with monoclonal antibody 17-C10. The natural log-transformed COMP data were analyzed using general linear models.Results. Serum COMP levels were significantly elevated (P ‫؍‬ 0.0001) in the age >65 group (mean ؎ SD 1,302.1 ؎ 496.7 ng/ml) versus the age 45-54 and age 55-64 groups (1,058.1 ؎ 432.4 and 1,038.6 ؎ 313.3, respectively). Serum COMP levels of the OA group were significantly higher than those of the control group (1,208.57 ؎ 487.47 ng/ml versus 1,061.83 ؎ 370.58 ng/ml; P ‫؍‬ 0.0093). Serum COMP levels also increased significantly with knee OA K/L grade (P ‫؍‬ 0.0047), knee OA laterality (P ‫؍‬ 0.0043), and number of knee and hip joints involved (P ‫؍‬ 0.0001). There was no significant difference in serum COMP levels by gender or obesity.Conclusion. We demonstrate that in a populationbased sample, serum COMP levels can distinguish an OA-affected subgroup from an unaffected subgroup and can reflect disease severity and multiple joint involvement in OA.Osteoarthritis (OA) is the most common joint disease known, affecting ϳ16 million individuals in the US alone. The disease is characterized by functional deterioration of the joint and loss of cartilage integrity. Current research has focused on quantification of cartilage degeneration products released into the synovial fluid and, subsequently, into the blood as a measure of disease severity and as a potential tool for diagnosing OA in its early stages. The ability to objectively determine OA status serologically would significantly enhance capabilities of identifying the disease with greater ease and at lower cost than current radiographic methods.Cartilage oligomeric matrix protein (COMP) is a 524-kd pentameric glycoprotein related to the thrombospondin family and found predominantly in cartilage, although recent studies have identified COMP in both tendon and synovium (1-3). Serum and synovial fluid levels of COMP have been analyzed for their potential as diagnostic or prognostic markers for detecting OA onset or progression. Results of synovial fluid COMP analyses have varied. Compared with reference groups of healthy individuals or athletes lacking knee pain,

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Serum concentrations of cartilage oligomeric matrix protein and bone sialoprotein in hip osteoarthritis: A one year prospective study

Cited by 92 publications

References 30 publications

Uncoupling of type II collagen synthesis and degradation predicts progression of joint damage in patients with knee osteoarthritis

Uncoupling of type II collagen synthesis and degradation predicts progression of joint damage in patients with knee osteoarthritis

What Is the Utility of Biomarkers for Assessing the Pathophysiology of Hip Osteoarthritis? A Systematic Review

Serum cartilage oligomeric matrix protein reflects osteoarthritis presence and severity: The Johnston county osteoarthritis project

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