University of Oulu

Koivisto, K.; Karppinen, J.; Haapea, M.; Järvinen, J.; Kyllönen, E.; Tervonen, O.; Niinimäki, J.; Alini, M.; Lotz, J.; Dudli, S.; Samartzis, D.; Risteli, J.; Majuri, M.-L.; Alenius, H.; Grad, S. The Effect of Zoledronic Acid on Serum Biomarkers among Patients with Chronic Low Back Pain and Modic Changes in Lumbar Magnetic Resonance Imaging. Diagnostics 2019, 9, 212.

The effect of zoledronic acid on serum biomarkers among patients with chronic low back pain and Modic changes in lumbar magnetic resonance imaging

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Author: Koivisto, Katri1; Karppinen, Jaro1,2,3; Marianne Haapea, Marianne Haapea1,2;
Organizations: 1Medical Research Center Oulu, Oulu University Hospital and University of Oulu, 90220 Oulu, Finland
2Center for Life Course Health Research, University of Oulu, 90220 Oulu, Finland
3Finnish Institute of Occupational Health, 90220 Oulu, Finland
4Research Unit of Medical Imaging, Physics and Technology, University of Oulu, 90220 Oulu, Finland
5AO Research Institute Davos, 7270 Davos Platz, Switzerland
6Department of Orthopaedic Surgery, University of California San Francisco, San Francisco, CA 94143, USA
7Center of Experimental Rheumatology, University Hospital Zurich, 8008 Zurich, Switzerland
8Department of Orthopedic Surgery, RUSH University, Chicago, IL 60612, USA
9Northern Finland Laboratory Centre NordLab, Oulu University Hospital, 90220 Oulu, Finland
10Institute of Environmental Medicine, Karolinska Institute, 17177 Stockholm, Sweden
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.3 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2019
Publish Date: 2020-02-17


The aim of the current study was to compare changes in serum biomarkers, including inflammatory mediators, signaling molecules, growth factors and markers of bone turnover after a single intravenous infusion of 5 mg zoledronic acid (ZA, a long-acting bisphosphonate; n = 20) or placebo (n = 20) among patients with Modic changes (MC) and chronic low back pain in a randomized controlled design. The MCs were classified into M1, predominating M1, predominating M2, and M2. We measured the serum concentrations of 39 biomarkers at baseline, and one month and one year after treatment. After Benjamini–Hochberg (B–H) correction, we observed significant differences in three biomarkers over one year: Interferon-γ-inducible protein (IP-10) had risen in the ZA group (p = 0.005), whereas alkaline phosphatase (AFOS) and intact procollagen I N-terminal propeptide (iPINP) had significantly decreased in the ZA group, but had not changed in the placebo group (p < 0.001 for both). Change in iPINP correlated with change in the volume of all MC and M1 lesions. ZA downregulated bone turnover markers as expected and, surprisingly, increased the chemokine IP-10 relative to placebo treatment. This adds to our knowledge of the effects of ZA on MC and the biomarkers that signal this process.

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Series: Diagnostics
ISSN: 2075-4418
ISSN-E: 2075-4418
ISSN-L: 2075-4418
Volume: 9
Issue: 4
Article number: 212
DOI: 10.3390/diagnostics9040212
Type of Publication: A1 Journal article – refereed
Field of Science: 3126 Surgery, anesthesiology, intensive care, radiology
317 Pharmacy
3121 General medicine, internal medicine and other clinical medicine
Funding: Novartis Pharma provided investigational medications for the study and supported the conduct of the trial (<USD 10 000). The study was supported by the Hansjörg Wyss Research Award (AOSpine). The funders played no role in the study design, data collection or analysis, decision to publish, or in the preparation of the manuscript.
Copyright information: © 2019 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 (