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Sensitization and Serological Biomarkers in Knee Osteoarthritis Patients With Different Degrees of Synovitis

Petersen, Kristian K. MSc, PhD; Siebuhr, Anne S. MSc, PhD; Graven-Nielsen, Thomas PhD, DMSc; Simonsen, Ole PhD, DMSc; Boesen, Mikael PhD; Gudbergsen, Henrik PhD; Karsdal, Morten MSc, PhD; Bay-Jensen, Anne C. MSc, PhD; Arendt-Nielsen, Lars PhD, DMSc

doi: 10.1097/AJP.0000000000000334
Original Articles

Objective: Synovitis is a frequent condition in knee osteoarthritis (KOA) and has been associated with pain. This study investigated the links between the pressure hyperalgesia, the clinical pain, the degree of the synovitis, inflammatory biomarkers, and tissue-specific biomarkers in KOA patients.

Materials and Methods: Fifty-eight KOA patients and 33 pain-free controls participated in this study. The patients were magnetic resonance imaging scanned, and the Boston-Leeds OA Knee Score (BLOKS, 0 to 3) was used to assess the degree of synovitis. The maximal knee pain intensity over the last 24 hours was scored on a visual analog scale (VAS). The pressure pain thresholds (PPTs) were assessed over the KOA-affected knee. Serological biomarkers were measured in fasting serum: high-sensitive C-reactive protein, matrix metalloproteinase–mediated degradation of CRP, and matrix metalloproteinase–mediated collagen type I, II, and III degradation (C1M [connective tissue], C2M [cartilage], C3M [synovial membrane]).

Results: Compared with controls, the KOA patients showed increased levels of C1M (P<0.02), C2M (P<0.001), and high-sensitive C-reactive protein (P<0.02), decreased level of C3M (P<0.03), and reduced PPTs (P<0.03). Patients with no (BLOKS 0) and moderate to severe (BLOKS 2&3) synovitis had significantly lower PPTs compared with mild synovitis (BLOKS 1). Significantly negative correlations were found between VAS and PPTs. No correlations were found between BLOKS and the VAS, PPT, or biomarkers.

Discussion: Patients without and with moderate to severe synovitis demonstrated local pressure hyperalgesia and increased degrees of: (1) systemic inflammation, (2) connective tissue degradation, (3) cartilage degradation, and (4) decreased synovial membrane degradation as compared with controls.

*SMI, Faculty of Medicine, Aalborg University

Orthopedic Surgery Research Unit, Research and Innovation Center, Aalborg University Hospital, Aalborg

Biomarkers and Research, Nordic Bioscience, Herlev

§Department of Radiology, Copenhagen University Hospital

Department of Rheumatology, The Parker Institute, Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark

Supported by the Danish Rheumatism Association, the Bevica Foundation, and the Danish Council for Technology and Innovation (09-052174).

A.S.S., A.C.B.-J., and M.K. are employees of Nordic Bioscience. M.K. holds stocks in Nordic Bioscience. The remaining authors declare no conflict of interest.

Reprints: Lars Arendt-Nielsen, PhD, DMSc, SMI, Department of Health Science and Technology, Aalborg University, Fredrik Bajers Vej 7 D-3, DK-9220 Aalborg, Denmark (e-mail:

Received August 7, 2015

Received in revised form January 29, 2016

Accepted November 14, 2015

Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.