Abstract
BackgroundExcessive cartilage degradation is a known characteristic of osteoarthritis (OA). Biochemical markers, such as uCTX-II, have been shown to be associated with disease severity, yet the tissue origin of CTX-II has been disputed. This analysis investigates the association between OA knee joints at different radiographic stages and pain categories with levels of uCTX-II and biomarkers of bone resorption and formation.MethodsBaseline data of two randomised clinical trials (NCT00486434 and NCT00704847) in patients with radiographic OA and presence of pain were analysed post hoc. A subgroup with available urine samples and evaluable radiographs for both knees (N = 1241) was analysed. Urine CTX-I, urine CTX-II and serum osteocalcin were analysed for associations with combined Kellgren-Lawrence (KL) scores, gender and pain for both knees to assess the contribution of joints at different stages.ResultsPain, BMI, age, gender and KL grade were all significantly associated with uCTX-II. The association between pain and CTX-II appeared to be driven by weight-bearing pain. The level of uCTX-II incrementally increased with higher radiographic severity of each knee. Levels of bone markers CTX-I and osteocalcin were both significantly associated with BMI and gender, but neither were associated with radiographic severity. Biomarker levels between male or female groups of identical KL scores were found to be higher in females compared to males in some but not all KL score groups.ConclusionsThese results indicate that levels of uCTX-II are independently associated with radiographic severity of OA and pain intensity. CTX-II was associated with weight-bearing pain, but not non-weight-bearing pain, independent of co-variates. Bilateral OA knee joints appear to contribute to uCTX-II levels in an incremental manner according to radiographic severity of single joints. The data suggest that biomarker differences between genders should be taken into account when evaluating these markers in the context of structural features of OA.
Highlights
Excessive cartilage degradation is a known characteristic of osteoarthritis (OA)
Reports have found associations between Urine C-telopeptide of cross-linked collagen type II (uCTX-II) and osteophyte area in painful knees, but not in knees with no pain, while associations found between uCTX-II and joint space width were similar in both knees with and without pain [16]
We found that the category of weight-bearing pain remained associated with CTX-II, while nonweight-bearing pain was not
Summary
Excessive cartilage degradation is a known characteristic of osteoarthritis (OA) Biochemical markers, such as uCTX-II, have been shown to be associated with disease severity, yet the tissue origin of CTX-II has been disputed. This analysis investigates the association between OA knee joints at different radiographic stages and pain categories with levels of uCTX-II and biomarkers of bone resorption and formation. While several reports supporting the suitability of uCTX-II as a robust measure of cartilage degradation exist, its reported association with known biomarkers of bone turnover, including the bone resorption marker C-telopeptide of cross-linked collagen type I (CTX-I) in urine (uCTX-I) and the bone formation marker serum (s-)osteocalcin (N-MID), has challenged the notion that uCTX-II reflects cartilage degradation [14]. Another report found an association between elevated uCTX-II and symptomatic OA and speculates that uCTX-II, among others, may reflect early changes in cartilage accounting directly or indirectly for knee pain [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
