Blood and urine biomarkers in osteoarthritis – an update on cartilage associated type II collagen and aggrecan markers

Abstract

Purpose of review Osteoarthritis (OA) is a painful disease for which drug development has proven difficult. One major reason for this is the heterogeneity of the disease and the current lack of operationalized means to distinguish various disease endotypes (molecular subtypes). Biomarkers measured in blood or urine, reflecting joint tissue turnover, have been developed and tested during the last decades. In this narrative review, we provide highlights on biomarkers derived from the two most studied and abundant cartilage proteins – type II collagen and aggrecan. Recent findings Multiple biomarkers assessing type II collagen degradation and formation, and aggrecan turnover have been developed. Several markers, such as uCTX-II, have been validated for their association with disease severity and prognosis, as well as pharmacodynamically used to describe the mode of action and efficacy of drugs in development. There is a great need for biomarkers for subdividing patients (i.e., endotyping) and recent scientific advances have not yet come closer to achieving this goal. Summary There is strong support for using biomarkers for understanding OA, reflecting degradation and formation of the joint tissues, focused on type II collagen and aggrecan. There is still a lack of in vitro diagnostics, in all contexts of use.

Osteoarthritis endotype discovery via clustering of biochemical marker data

“…Moreover, we focused on biochemical markers measured at the baseline of the study, and not their longitudinal changes, as this analysis would be more useful to inform future clinical trials. Longitudinal monitoring of biomarkers can give insight in the pharmacodynamic effects or provide early proof of effectiveness of a compound in interventional clinical trials, however often fail to predict progression in the study population in these trials 34 40–42. Therefore, although longitudinal monitoring of individual biomarkers are only modestly predictive (if at all) of knee OA progression, they might have some utility as patient stratification like described herein for enriching OA trials for progressors 29…”

Cartilage Acidic Protein 1 in Plasma Associates With Prevalent Osteoarthritis and Predicts Future Risk as Well as Progression to Joint Replacements: Results From the UK Biobank Resource

“…As such an important structural protein in cartilage, ACAN is a strong candidate biomarker, with support from this study. Markers of ACANs degradation/remodeling products have been developed (9). NCAN, like ACAN, is a chondroitin sulphate proteoglycan but with an unknown function.…”

Understanding the role of physical activity on the pathway from intra-articular knee injury to post-traumatic osteoarthritis disease in young people: a scoping review protocol

“…For molecular indicators of disease processes, OsteoArthritis Research Society International (OARSI) recommended biomarkers121 will be included alongside other biomarkers of cartilage metabolism which have been deemed of interest in previous reviews due to their association with joint health (online supplemental material 3). 122–125 This list of outcome measures is not exhaustive and will be added to if other relevant outcomes are identified during Stage 2: identifying relevant studies.…”