Background Among the currently available biochemical markers for osteoarthritis (OA), urinary collagen type II C-telopeptide (uCTX-II) is one of the most frequently investigated markers1. Much research has been performed into the performance of uCTX-II, but most of it in relatively small cohort studies1. Therefore, we performed a meta-analysis to summarize uCTX-II studies in a quantitative way.
Objectives To perform a meta-analysis of the performance of uCTX-II as a biomarker for diagnosing knee osteoarthritis (KOA) and its association with radiographic KOA severity. Furthermore, to look for patient and study characteristics that determine uCTX-II performance.
Methods Medline and Embase databases were searched for studies into uCTX-II levels in adult subjects with radiographic KOA according to the Kellgren and Lawrence (K&L) classification system. uCTX-II levels were compared between subjects with KOA K&L ≥2 versus healthy control subjects and between subjects with KOA K&L 2 versus K&L 3–4 (i.e. moderate vs severe KOA). Controls were either selected based on lack of knee symptoms, based on K&L score, or were randomly selected from the general population. Differences between KOA subgroups were expressed as standardized mean differences (SMD). Subgroup analyses were performed to compare uCTX-performance between genders, ethnicities, and large and small studies. Differences between subgroups were considered relevant when SMDs differed >25% between groups.
Results 2035 Studies were screened for eligibility, of which ten studies were included. A moderate pooled SMD of 0.52 (confidence interval (CI): 0.40–0.65, P<0.0001) was found for subjects with KOA K&L ≥2 versus controls, based on ten SMDs. For K&L3–4 versus K&L2 a moderate pooled SMD of 0.47 (CI: 0.32–0.63, P<0.0001) was found, based on five SMDs. No indications for publication bias were identified using funnel plots. Subgroup analyses of the K&L ≥2 versus control comparison showed that uCTX-II performs better in women as compared to men and in Caucasian subjects as compared to other ethnicities. Study size did not influence the pooled SMD. Subgroup analysis was considered infeasible for the K&L 2 versus K&L 3–4 comparison due to a limited number of studies.
Conclusions This is the first meta-analysis of uCTX-II performance in subjects with radiographic KOA. It appeared that uCTX-II levels can distinguish with moderate strength between radiographic KOA subjects and controls. Moreover, uCTX-II levels are consistently increased in severe versus moderate radiographic KOA. Female gender and Caucasian ethnicity were found to enhance uCTX-II performance in distinguishing radiographic KOA from controls. Yet, the number of studies was relatively small and criteria for KOA and control subjects differed between studies.
Van Spil WE, DeGroot J, Lems WF, Oostveen JCM, Lafeber FPJG. Serum and urinary biochemical markers for knee and hip-osteoarthritis: A systematic review applying the consensus BIPED criteria. Osteoarthr Cartil 2010;18(5):605–12. Doi: 10.1016/j.joca.2010.01.012.
Disclosure of Interest None declared