University of Oulu

Dudli, S.; Ballatori, A.; Bay-Jensen, A.-C.; McCormick, Z.L.; O’Neill, C.W.; Demir-Deviren, S.; Krug, R.; Heggli, I.; Juengel, A.; Karppinen, J.; Brunner, F.; Farshad, M.; Distler, O.; Lotz, J.C.; Fields, A.J. Serum Biomarkers for Connective Tissue and Basement Membrane Remodeling Are Associated with Vertebral Endplate Bone Marrow Lesions as Seen on MRI (Modic Changes). Int. J. Mol. Sci. 2020, 21, 3791.

Serum biomarkers for connective tissue and basement membrane remodeling are associated with vertebral endplate bone marrow lesions as seen on MRI (Modic changes)

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Author: Dudli, Stefan1; Ballatori, Alexander2; Bay-Jensen, Anne-Christine3;
Organizations: 1Center of Experimental Rheumatology, University of Zurich, Balgrist Campus, 8008 Zurich, Switzerland
2Department of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA 94142, USA
3Immuno-Science, Nordic Bioscience, Biomarkers and Research, 2730 Herlev, Denmark
4Medical Research Center Oulu, Oulu University Hospital and University of Oulu, 90220 Oulu, Finland
5Center for Life Course Health Research, University of Oulu, 90220 Oulu, Finland
6Finnish Institute of Occupational Health, 90220 Oulu, Finland
7Department of Physical Medicine and Rheumatology, Balgrist University Hospital, 8008 Zurich, Switzerland
8Department of Orthopeadic Surgery, Balgrist University Hospital, 8008 Zurich, Switzerland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.7 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2020
Publish Date: 2020-07-07


Vertebral endplate bone marrow lesions, visualized on magnetic resonance imaging (MRI) as Modic changes (MC), are associated with chronic low back pain (cLBP). Since guidelines recommend against routine spinal MRI for cLBP in primary care, MC may be underdiagnosed. Serum biomarkers for MC would allow early diagnosis, inform clinical care decisions, and supplement treatment monitoring. We aimed to discover biomarkers in the blood serum that correlate with MC pathophysiological processes. For this single-site cross-sectional study, we recruited 54 subjects with 38 cLBP patients and 16 volunteers without a history of LBP. All subjects completed an Oswestry Disability Index (ODI) questionnaire and 10-cm Visual Analog Score (VAS) for LBP (VASback) and leg pain. Lumbar T1-weighted and fat-saturated T2-weighted MRI were acquired at 3T and used for MC classification in each endplate. Blood serum was collected on the day of MRI. Biomarkers related to disc resorption and bone marrow fibrosis were analyzed with enzyme-linked immune-absorbent assays. The concentration of biomarkers between no MC and any type of MC (AnyMC), MC1, and MC2 were compared. The Area Under the Curve (AUC) of the Receiver Operating Characteristics were calculated for each biomarker and for bivariable biomarker models. We found that biomarkers related to type III and type IV collagen degradation and formation tended to correlate with the presence of MC (p = 0.060–0.088). The bivariable model with the highest AUC was PRO-C3 + C4M and had a moderate diagnostic value for AnyMC in cLBP patients (AUC = 0.73, specificity = 78.9%, sensitivity = 73.7%). In conclusion, serum biomarkers related to the formation and degradation of type III and type IV collagen, which are key molecules in bone marrow fibrosis, correlated with MC presence. Bone marrow fibrosis may be an important pathophysiological process in MC that should be targeted in larger biomarker and treatment studies.

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Series: International journal of molecular sciences
ISSN: 1661-6596
ISSN-E: 1422-0067
ISSN-L: 1661-6596
Volume: 21
Issue: 11
Article number: 3791
DOI: 10.3390/ijms21113791
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This study was supported by the VELUX Foundation grant number 1170 (S.D.), the Balgrist Foundation, (S.D.) and National Institutes of Health grants R01 AR070198 (A.J.F.), R01 AR063705 (J.C.L.), and P30 AR066262 (J.C.L.).
Copyright information: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (