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Associations of CTX-II with biochemical markers of bone turnover raise questions on its tissue origin: data from CHECK, a cohort study of early osteoarthritis
  1. Willem E van Spil1,
  2. K Wiepke Drossaers-Bakker2,
  3. Floris PJG Lafeber1
  1. 1Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
  2. 2Arthritis Center Twente, Medical Spectrum Twente, Enschede, The Netherlands
  1. Correspondence to Willem E van Spil, Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Heidelberglaan 100, PO Box 85500, 3508 GA, Utrecht, The Netherlands; w.e.vanspil{at}


Objective CTX-II (C-terminal telopeptide of type II collagen) has been put forward as a marker of collagen type II degradation being part of osteoarthritis. In this study, the authors describe similarities between CTX-II and bone markers arguing against CTX-II as a marker of (solely) cartilage degradation.

Methods uCTX-II, the bone markers uCTX-I, uNTX-I, sPINP, and sOC (C-terminal and N-terminal telopeptides of collagen I, aminoterminal propeptide of type I procollagen, and osteocalcin, respectively), and other (candidate) cartilage markers sCOMP, sCS846, and sPIIANP (cartilage oligomeric matrix protein, chondroitin sulphate 846 and type IIA collagen N-propeptide, respectively) were assessed by ELISA in CHECK (Cohort Hip and Cohort Knee), a cohort of 1002 individuals with early pain and/or stiffness in knee and/or hip.

Results uCTX-II was more strongly associated with the bone markers than with the other cartilage markers, while the other cartilage markers were not so strongly associated with the bone markers. Moreover, both uCTX-II and bone markers but not the other cartilage markers showed an abrupt menopausal shift in women aged 48-53 years, also when adjusted for age and BMI.

Conclusion The similarities between uCTX-II and bone markers could be attributable to a link between cartilage and bone metabolism through metabolic and biomechanical mechanisms. However, other cartilage markers were hardly associated with uCTX-II and did not show such evident associations with bone markers. uCTX-II has unique relations with bone markers as compared to other cartilage markers and might reflect bone rather than cartilage metabolism. More thorough molecular validation of uCTX-II is required.

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  • Funding This study was supported by the Dutch Arthritis Association.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval CHECK received approval from the medical ethics committees of all involved medical centres.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Additional unpublished data can be obtained from the corresponding author on request.