Increased urinary excretion of C-telopeptides of type II collagen (CTX-II) predicts cartilage loss over 21 month by MRI

Nordic Bioscience A/S, Herlev Hovedgade 207, DK-2730 Herlev, Denmark.
Osteoarthritis and Cartilage (Impact Factor: 4.17). 09/2008; 17(3):384-9. DOI: 10.1016/j.joca.2008.07.009
Source: PubMed


Osteoarthritis (OA) is characterized by increased bone and cartilage metabolism leading to joint damage. The urinary excretion of C-telopeptides of type II collagen (CTX-II) has earlier predicted progression in radiographic OA (ROA)--useful for participant selection in clinical studies of potential disease modifying OA drugs (DMOADs). We investigated the longitudinal interrelationship between CTX-II and knee cartilage volume quantified from magnetic resonance imaging (MRI).
We followed 158 subjects [48% females, 36 with knee ROA at baseline (BL)] for 21 months. The Kellgren and Lawrence (KL) index and joint space width were assessed from radiographs (acquired load-bearing, semi-flexed). MRI scans were acquired from a 0.18 T Esaote scanner (40 degrees flip angle (FA), TR 50 ms, TE 16 ms, scan time 10 min, resolution 0.7 mm x 0.7 mm x 0.8 mm) and medial tibial and femoral cartilage volume was quantified. Radiographs and MRI were acquired at BL and follow-up. Fasting morning urine samples (second void) were collected for BL CTX-II measurement.
CTX-II was 56% higher in ROA subjects (P=0.0001). In addition, elevated BL CTX-II was associated with radiographic progression (by KL or joint space narrowing) although not statistically significant. Contrarily, elevated BL CTX-II predicted longitudinal cartilage loss by MRI (middle/high tertiles had odds ratios 4.0/3.9, P<0.01) corresponding to 3.1% increased yearly cartilage loss.
Prognostic markers in study selection criteria must ensure that placebo-treated participants progress to enable efficacy demonstration. And efficacy markers must allow progression detection within the study period. Our results support applying CTX-II for selection of high risk subjects and applying the fully automatic MRI-based framework for quantification of cartilage loss.

12 Reads
  • Source
    • "As we can see from this partial list (Table 2), many marker associations to OA diagnosis have been described. These include proteinbased markers from blood [serum hyaluronic acid (sHA), serum cartilage oligomeric matrix protein (sCOMP)], from urine (uCTX-II) and gene-based markers [Cibere et al. 2009; Dam et al. 2009a; Deberg et al. 2005a, 2005b; Fernandez-Moreno et al. 2008; Karsdal et al. 2010; Kraus et al. 2010; Meulenbelt et al. 2006; Rego-Perez et al. 2008]. For example, when Sharif and colleagues examined tibiofemoral OA versus patellofemoral OA, they were able to show a relationship between elevated serum COMP and tibiofemoral OA, specifically highlighting the diagnostic discrimination that might be obtained using biomarkers [Sharif et al. 2006]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Personalized medicine is a much talked about subject that is a timely and important development to healthcare in general and also specifically for patients affected by osteoarthritis. This review uses biomarker examples pertinent to osteoarthritis to highlight the current status of the field, while also highlighting probable future developments. It is not meant to be an exhaustive account. The BIPED(s) [Burden of disease, Investigative, Prognosis, Efficacy, Diagnosis (safety)] classification system is used to organize the discussion of examples. Biomarkers pertaining to burden, investigation, prognosis, efficacy, diagnosis and safety are highlighted. The examples are followed by a discussion of issues related to interpretation and application of biomarker results and approaches to solve the challenges interpretation faces, including graphical, mathematical and synthetic representations. Through this review, it is hoped that a better appreciation can be gained of the potential and pitfalls of personal medicine in the care of patients with osteoarthritis.
    Therapeutic advances in musculoskeletal disease 04/2013; 5(2):67-75. DOI:10.1177/1759720X12470752
  • Source
    • "The effects of nasal CT on OA is evaluated with MRI scans and some beneficial effects on cartilage defects were observed in the MFC area. Although a linear relationship was reported between urinary excretion of CTX-II and MRI findings of the cartilage defect in patients with OA (30), there are no studies evaluating the effects of calcitonin on MRI findings of OA. The beneficial effects of calcitonin on MRI findings of OA in the present study was thought to be related to the fact that calcitonin decreases the degradation of calcitonin, a major component of the cartilage. "
    [Show abstract] [Hide abstract]
    ABSTRACT: This study was conducted to determine if nasal salmon calcitonin has additional beneficial effects on clinical symptoms, serum NO, IL-1β, matrix metalloproteinase 3, urinary C-terminal telopeptide type II collagen (CTX-II) levels and MRI findings in knee osteoarthritis (OA) when used concomitantly with exercise therapy. Fifty female patients with knee OA were randomized into two groups. The first group (n = 30) received 200 IU/day nasal salmon calcitonin and a home exercise program; the second group (n = 20) received a home exercise program for 6 months. Compared with baseline,while significant improvements were observed in visual analogue scale (VAS), WOMAC pain, physical function scores, 20-m walking time (P < 0.001) and WOMAC stiffness score (P = 0.041) in the first group, walking and resting VAS, and WOMAC physical function scores were improved (P = 0.029) in the second group after treatment. Significantly increased levels of serum NO and urinary CTX-II (P < 0.001) and significant improvements in the area of medial femoral condyle (P < 0.05) were noted only in the first group. There were significant differences in VAS activation values (P = 0.032) and NO levels (P < 0.001) in the favor of the first group. In conclusion, nasal salmon calcitonin may have possible chondroprotective effects besides its known effects on symptoms in patients with knee OA.
    Journal of Korean medical science 11/2012; 27(11):1405-10. DOI:10.3346/jkms.2012.27.11.1405 · 1.27 Impact Factor
  • Source
    • "This fragment is used as an urinary marker of cartilage degradation because it was found to correlate with cartilage loss in animal models of OA [52] and increased CTX-II levels in patients with OA compared with controls were reported [53]. Correlations of CTX-II with clinical assessment [54] and X-rays [55] or MRI [56, 57] evaluation of human OA have been found. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Several studies dealing with the pathomechanisms of OA refer to MMP-1, -3, -7, -8, and -13 whereas a smaller number of investigations have pointed out the pathogenic role of gelatinases in OA. These gelatinases are best known for their involvement in pulmonary, myocardial, and neoplastic disease but they are emerging as important proteases implicated in the OA progression. This paper highlights the role of the gelatinases as emerging factors in OA pathogenesis through the regulation of subchondral bone resorption and microvascular invasion. The most significant new findings over the last year that add to our knowledge of the activity of these proteins in OA have been reported.
    07/2012; 2012:834208. DOI:10.1155/2012/834208
Show more


12 Reads
Available from