Osteoarthritis Year in Review 2016: biomarkers (biochemical markers) A. Mobasheri, A.-C. Bay-Jensen, W.E. van Spil, J. Larkin, M.C. Levesque  Osteoarthritis and Cartilage  Volume 25, Issue 2, Pages 199-208 (February 2017) DOI: 10.1016/j.joca.2016.12.016 Copyright © 2016 The Authors Terms and Conditions

Fig. 1 New definition of OA, as endorsed by OARSI. This figure highlights the relationships between the disease and illness components of OA. The molecular component represents the silent and asymptomatic early stage of OA. Molecular changes precede the anatomic and physiologic aspects by years or even decades. This creates a challenge for detecting the disease early and an opportunity for finding new early marker of disease. Figure adapted from24 with the kind permission of Dr Virginia Kraus. Osteoarthritis and Cartilage 2017 25, 199-208DOI: (10.1016/j.joca.2016.12.016) Copyright © 2016 The Authors Terms and Conditions

Fig. 2 OA phenotypes. OA is a heterogeneous disease with a variety of pathophysiologic drivers leading to multiple phenotypes, many of which may overlap in patients. Each phenotype may be treated and targeted differently, paving the way for patient “stratification” and the development of “precision” medicines for OA. Some of these will be amenable to pharmacologic intervention but others may be less likely to respond to drugs. Osteoarthritis and Cartilage 2017 25, 199-208DOI: (10.1016/j.joca.2016.12.016) Copyright © 2016 The Authors Terms and Conditions

Fig. 3 Application of the biomarker toolbox in OA drug discovery and development. This schematic highlights the mutual interdependency of the biomarker testing and drug development pipelines. By linking an OA biomarker to a complementary endpoint industry can make rational decisions about the continuity of preclinical studies and the scale of OA clinical trials. Biomarkers can be used to identify responders and non-responders and quantify clinical efficacy and patient stratification (i.e., identification of those in need of treatment and selection of patients most likely to respond to treatment). Osteoarthritis and Cartilage 2017 25, 199-208DOI: (10.1016/j.joca.2016.12.016) Copyright © 2016 The Authors Terms and Conditions