Background Biochemical markers (biomarkers) are proposed to reflect certain metabolic pathways in health and disease. However, actual molecular validity of biomarkers is often not definite.
Objectives uCTX-II has been put forward as a marker of collagen type II degradation being part of cartilage degradation in osteoarthritis and is used as (surrogate) end point in therapeutic trials. Here we present data that argue against this assumption and warrant more cautious interpretation of uCTX-II levels.
Methods uCTX-II, and the bone biomarkers uCTX-I, uNTX-I, sPINP and sOC as well as the cartilage markers sCOMP, sCS846, and sPIIANP were assessed by ELISA in baseline samples of CHECK (Cohort Hip & Cohort Knee), a cohort of 1002 individuals with early complaints of pain and/or stiffness in knee and/or hip. Correlations between biomarkers and between biomarkers and demographics were investigated through multiple linear regression analysis.
Results uCTX-II was more strongly correlated with bone markers than with the cartilage markers, while the cartilage markers did not show such strong correlations with the bone markers. Moreover, both uCTX-II and bone markers but not the other cartilage markers showed an abrupt menopausal shift in woman at the age of 50-55 years, also when adjusted for age and BMI.
Conclusions The increased bone marker levels in postmenopausal women are in accordance with the well-known increase in bone turnover after menopause. The many 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 correlated with uCTX-II and did not show such evident correlations with bone markers. These data suggest that uCTX-II has unique relations with bone markers as compared to other cartilage markers and reflects bone rather than cartilage metabolism. Accordingly, other authors have suggested osteoclastic resorption of calcified cartilage as the major origin of uCTX-II. More thorough molecular validation of uCTX-II is required to better define its origin. Until then, uCTX-II levels should be interpreted cautiously.
This study was funded by CHECK, an initiative of the Dutch Arthritis Association.
Disclosure of Interest None Declared