Biomarkers for osteoarthritis: Current position and steps towards further validation
Best practice & research. Clinical rheumatology (Impact Factor: 2.6). 02/2014; 28(1):61-71. DOI: 10.1016/j.berh.2014.01.007
Historically disease knowledge development and treatment innovation in osteoarthritis (OA) has been considered to be slow. One of the many reasons purported as responsible for this slow pace has been the alleged lack of valid and responsive biomarkers to ascertain efficacy, which itself has been dependent upon the slow evolution of the understanding of the complex nature of joint tissue biology. This narrative review outlines the rationale for why we need OA biomarkers with regard to biomarker validation and qualification. The main biomarkers in current development for OA are biochemical and imaging markers. We describe an approach to biomarker validation and qualification for OA clinical trials that has recently commenced with the Foundation of NIH OA Biomarkers Consortium study cosponsored by the Osteoarthritis Research Society International (OARSI). With this approach we endeavor to identify, develop, and qualify biological markers (biomarkers) to support new drug development, preventive medicine, and medical diagnostics for osteoarthritis.
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ABSTRACT: Objective: To assess the association between pain mechanisms (sensitization) and biochemical markers for cartilage, bone, and inflammation in patients with knee pain. Methods: The study group comprised 281 patients with different degrees of knee pain intensity and radiographic findings (using the Kellgren/Lawrence [K/L] scale). The following structurally related serologic biomarkers were measured in serum: high-sensitivity C-reactive protein (hsCRP), matrix metalloproteinase (MMP)-mediated breakdown of CRP (CRPM), MMP-mediated degradation of type I collagen (C1M), C2M, and C3M. Pressure-pain thresholds (PPT) (peripheral and spreading sensitization), temporal summation of pain, and conditioning pain modulation (CPM) (with the latter 2 biomarkers representing generalized sensitization) were assessed. For each pain parameter, the patients were categorized as most sensitized or least sensitized. Results: Correlations were observed between the pain biomarkers PPT, temporal summation, and CPM and maximal pain intensity during the last 24 hours. Significant associations between most of the serologic biomarkers were observed. A high CRPM level was associated with centralized sensitization (temporal summation and CPM). None of the serologic markers correlated with the intensity or duration of knee pain, and only hsCRP correlated with the K/L grade. The most-sensitized group contained more women than men, and the least-sensitized group contained more men than women. Conclusion: A platform of mechanistic pain biomarkers in combination with structure-related serologic biomarkers provides new possibilities for understanding how osteoarthritis-related structural features may be associated with pain and pain sensitization. This study showed significant correlations between central pain sensitization and CRPM as a possible measure for chronic inflammation. Future pain association studies should include biomarkers representing the local joint environment more specifically.Arthritis and Rheumatology 08/2014; 66(12). DOI:10.1002/art.38856
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ABSTRACT: Biochemical and pain biomarkers can be applied to patients with painful osteoarthritis profiles and may provide more details compared with conventional clinical tools. The aim of this study was to identify an optimal combination of biochemical and pain biomarkers for classification of patients with different degrees of knee pain and joint damage. Such profiling may provide new diagnostic and therapeutic options. A total of 216 patients with different degrees of knee pain (maximal pain during the last 24 hours rated on a visual analog scale [VAS]) (VAS 0-100) and 64 controls (VAS 0-9) were recruited. Patients were separated into 3 groups: VAS 10 to 39 (N = 81), VAS 40 to 69 (N = 70), and VAS 70 to 100 (N = 65). Pressure pain thresholds, temporal summation to pressure stimuli, and conditioning pain modulation were measured from the peripatellar and extrasegmental sites. Biochemical markers indicative for autoinflammation and immunity (VICM, CRP, and CRPM), synovial inflammation (CIIIM), cartilage loss (CIIM), and bone degradation (CIM) were analyzed. WOMAC, Lequesne, and pain catastrophizing scores were collected. Principal component analysis was applied to select the optimal variable subset, and cluster analysis was applied to this subset to create distinctly different knee pain profiles. Four distinct knee pain profiles were identified: profile A (N = 27), profile B (N = 59), profile C (N = 85), and profile D (N = 41). Each knee pain profile had a unique combination of biochemical markers, pain biomarkers, physical impairments, and psychological factors that may provide the basis for mechanism-based diagnosis, individualized treatment, and selection of patients for clinical trials evaluating analgesic compounds. These results introduce a new profiling for knee OA and should be regarded as preliminary.Pain 01/2015; 156(1):96-107. DOI:10.1016/j.pain.0000000000000011 · 5.21 Impact Factor
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ABSTRACT: The 7(th) OARSI International Workshop on Osteoarthritis Imaging was held in Reykjavik, Iceland, from July 9-12, 2014; attracting attendees from academia, pharmaceutical and MRI industries, as well as a large number of young investigators. The Workshop program consisted of six modules, including imaging in OA, imaging and pain in OA, new techniques in imaging, risk factors and structural outcomes, anti-nerve growth factor (a-NGF) therapy, and joint replacement. A wealth of data was presented from OA researchers from all over the world and participants gained insightful knowledge on up-to-date research work focusing on imaging of OA. This paper presents a summary of the salient points from the workshop. Identifying the appropriate imaging modality and parameters will be critical for ensuring responsive, reproducible and reliable outcomes for clinical trials. Continued efforts from the OA research community are needed to establish the most effective use of imaging in OA clinical trials, including anti-NGF therapy and joint replacement trials, and to validate newer imaging techniques such as compositional MRI for use in the future clinical trials. Copyright © 2015. Published by Elsevier Ltd.Osteoarthritis and Cartilage 02/2015; 23(6). DOI:10.1016/j.joca.2015.02.004 · 4.17 Impact Factor
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