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.

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Available from: Morten Karsdal, Oct 02, 2015
    • "In a large study including individuals from the Rotterdam Study, the Genetics osteo-Arthritis and Progression study, the Chingford Study, and the TwinsUK cohort, those with higher levels of uCTX-II were at higher risk for radiographic incidence of knee OA and there was more than four times higher risk for incidence of hip osteoarthritis[5]. Progression of knee and/or hip OA was positively associated with uCTX-II in 7 stud- ies[5,6,11,15,21,23,25]although in one small study the association was not significant[15]. In a small RCT (n = 120), after 30 months follow-up of knee OA in female patients, no association was found between uCTX-II and progression of knee OA, defined as JSN ≥ 0.33 mm[31]. "
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