Biological markers in osteoarthritis

Abstract

Osteoarthritis (OA) is considered as a chronic disease with a long “silent” period. The diagnosis is generally based on clinical symptoms and radiographic changes. However X-ray has a poor sensitivity and a relatively large precision error that does not allow an early detection of OA or the monitoring of joint damage progression. The limitations of the tools that are currently available for OA assessment have been the impetus to identify specific biological markers that reflect quantitative and dynamic variations in joint remodeling. Research has focused on the structural components of cartilage matrix, especially type II collagen degradation markers. In spite of a significant increase of some markers in individuals with early stage of OA, the large overlap with control subjects indicates that the current biomarkers used alone have limited diagnostic potential. However, the combination of specific markers seems to improve the prediction of disease progression at the individual level. Several types of treatment have been investigated but the lack of medications with definitively demonstrated chondroprotective activity has limited the assessment of the potential role of biomarkers for monitoring patients' responses to the treatment of OA. In this review, we will use the BIPED classification that appeared in 2006 for OA markers to describe the potential usage of a given marker [5].

This article is part of a Special Issue entitled "Osteoarthritis".

Introduction

Osteoarthritis (OA) is the most frequent chronic musculoskeletal disease affecting approximately 40% of adults aged over 70 years [1]. It is considered as a slowly progressive disease altering all tissues of the affected joint and appearing as a degradation of cartilage, the hallmark of OA, but also a mild-to-moderate synovial inflammation and an alteration of subchondral bone structure. OA is considered as a chronic disease with a long “silent” period that can be compared to a heart attack or stroke that represents the end stage of long-simmering cardiovascular disease [2]. Until now, the gold standard to estimate the extent of the disease is plain radiography. During the last years, radiographic positioning has been improved as well as other elements of the radiographic protocol but the relatively large precision error and its poor sensitivity do not allow early detection of joint degradation and the monitoring of potential treatments. Magnetic resonance imaging (MRI) is a more sensitive imaging method but it is still used less often than X-rays due to cost and limited availability. MRI scans show cartilage, bone, synovial effusion and ligaments. Finally, arthroscopy allows a direct view of the cartilage surface but even if it is a minimal invasive surgical procedure it cannot be routinely applied to large number of patients.

Conventional laboratory markers such as high sensitive C-reactive protein (hsCRP) have been shown to be elevated in early phases of OA [3] suggesting the presence of low grade inflammation, which supports a pathophysiological role of inflammation at early stages of the disease process. However because BMI is highly correlated with hsCRP, when both obesity and hsCRP are evaluated simultaneously, hsCRP does not remain significantly associated with incident knee OA [4]. Given the limitations of the tools that are currently available for OA assessment, there is considerable interest in the identification of specific biological markers that reflect quantitative and dynamic variations in joint tissue remodeling.

In this revue, we briefly describe the tissue origin and focus on the main characteristics of markers using the BIPED classification [5]. For additional considerations regarding to the notions of qualification and validation of biomarkers, the reader can refer to the revue published last year by the OARSI FDA Osteoarthritis Biomarkers Working Group [6].