Osteoarthritis year in review 2019: biomarkers (biochemical markers)

Abstract

Results: Over two hundred new biomarker-related papers were published during the literature search period. Some papers identified new biomarkers whereas others explored the biological properties and clinical utility of existing markers. There were specific references to several adipocytokines including leptin and adiponectin. ADAM Metallopeptidase with Thrombospondin Type 1 motif 4 (ADAMTS-4) and aggrecan ARGS neo-epitope fragment (ARGS) in synovial fluid (SF) and plasma chemokine (CeC motif) ligand 3 (CCL3) were reported as potential new knee biomarkers. New and refined proteomic technologies and novel assays including a fluoro-microbead guiding chip (FMGC) for measuring C-telopeptide of type II collagen (CTX-II) in serum and urine and a novel magnetic nanoparticle-based technology (termed magnetic capture) for collecting and concentrating CTX-II, were described this past year. Conclusion: There has been steady progress in osteoarthritis (OA) biomarker research in 2016. Several novel biomarkers were identified and new technologies have been developed for measuring existing biomarkers. However, there has been no "quantum leap" this past year and identification of novel early OA biomarkers remains challenging. During the past year, OARSI published a set of recommendations for the use of soluble biomarkers in clinical trials, which is a major step forward in the clinical use of OA biomarkers and bodes well for future OA biomarker development.

An Evidence-Based Systematic Review of Human Knee Post-Traumatic Osteoarthritis (PTOA): Timeline of Clinical Presentation and Disease Markers, Comparison of Knee Joint PTOA Models and Early Disease Implications

“…However, while this review and other reviews and consensus reports suggest that such biochemical biomarkers could be used as indicators of PTOA progression [ 229 , 230 , 231 ], so far adequate validation, e.g., of MMP-3, is still lacking. As we show in this review, while MMP-3 as well as other biochemical biomarkers remain present for extensive periods of time in the SF after injury, and SF MMP-3 levels even correlated with IL-6 levels in the SF up to 7 months after knee injury [ 31 ], SF analysis is not always clinically feasible or SF is not reliably gained.…”

Identification of tissue-dependent proteins in knee OA synovial fluid

“…In the search of diagnostic targets that are capable of identifying biomolecular changes in knee joint homeostasis, important efforts have been made to understand the proteomic composition of synovial fluid and to identify OA-related changes in its composition 10,19,27e29 . However, the origin of OA-related alterations in the proteomic composition of synovial fluid remained poorly documented and biochemical markers generally lacked specificity to certain joint tissues 30 . In our study we identified 62 proteins with a significantly higher abundance in synovial fluids of osteoarthritic knees.…”

Endogenous anandamide and self-reported pain are significantly reduced after a 2-week multimodal treatment with and without radon therapy in patients with knee osteoarthritis: a pilot study

“…Many effects of radon therapy have been shown for systemic inflammatory diseases (Falkenbach et al 2005;Lange et al 2016;Shehata et al 2006;van Tubergen et al 2001). OA is primarily considered a non-inflammatory degenerative disease, although the influence of inflammatory components is more and more recognized, and radon therapy might simply be without apparent measurable effect in the observed variables in OA patients.…”

“…Several randomized controlled clinical trials report significant long-term improvement of pain after radon balneology or radon speleotherapy in patients with degenerative spinal disease, rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis (Annegret and Thomas 2013;Falkenbach et al 2005;Becker 2003;Cuttler 2020;Franke et al 2007;Kojima et al 2018;Kuciel-Lewandowska et al 2020;van Tubergen et al 2001;van Tubergen and van der Linden 2002). Hormetic effects on DNA repair, the immune system, the antioxidant, or the endocrine system have been proposed; however, the biological mechanisms underlying the potential Rn effects still remain elusive (Galvez et al 2018;Kuciel-Lewandowska et al 2018;Lange et al 2016;Nagy et al 2009;Shehata et al 2006;Yamaoka et al 2005;Ruhle et al 2019;Ruhle et al 2017;Wunderlich et al 2019).…”