University of Oulu

Koivisto, K., Järvinen, J., Karppinen, J., Haapea, M., Paananen, M., Kyllönen, E., Tervonen, O., Niinimäki, J. (2017) The effect of zoledronic acid on type and volume of Modic changes among patients with low back pain. BMC Musculoskeletal Disorders, 18 (1). doi:10.1186/s12891-017-1632-z

The effect of zoledronic acid on type and volume of Modic changes among patients with low back pain

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Author: Koivisto, Katri1; Järvinen, Jyri2; Karppinen, Jaro1,3,4;
Organizations: 1Medical Research Center Oulu, Oulu University Hospital and University of Oulu
2Institute of Diagnostics, Department of Diagnostic Radiology, Oulu University Hospital
3Center for Life Course Health Research, University of Oulu
4Finnish Institute of Occupational Health
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1 MB)
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Language: English
Published: Springer Nature, 2017
Publish Date: 2017-12-04


Background: Modic changes (MC) are associated with low back pain (LBP). In this study, we compared changes in size and type of MC, after a single intravenous infusion of 5 mg zoledronic acid (ZA) or placebo, among chronic LBP patients with MC on magnetic resonance imaging (MRI), and evaluated whether the MRI changes correlate with symptoms.

Methods: All patients (N = 19 in ZA, 20 in placebo) had MRI at baseline (0.23–1.5 T) and at one year (1.5–3 T). We evaluated the level, type and volume of all the MC. The MC were classified into M1 (M1 (100%)), predominating M1 (M1/2 (65:35%)) or predominating M2 (M1/2 (35:65%)), and M2 (M2 (100%)). The first two were considered M1-dominant, and the latter two M2-dominant. Volumes of M1 and M2 were calculated separately for the primary MC, which was assumed to cause the symptoms, and the other MC. We analysed the one-year treatment differences in M1 and M2 volumes using analysis of covariance with adjustments for age, sex, body mass index, and smoking. The correlations between the MRI changes and the changes in LBP symptoms were analysed using Pearson correlations.

Results: In the ZA group, 84.2% of patients had M1-dominant primary MC at baseline, compared to 50% in the placebo group (p = 0.041). The primary MC in the ZA group converted more likely to M2-dominant (42.1% ZA, 15% placebo; p = 0.0119). The other MC (15 ZA, 8 placebo) were on average 42% smaller and remained largely M2-dominant. The M1 volume of the primary MC decreased in the ZA group, but increased in the placebo group (−0.83 cm³ vs 0.91 cm³; p = 0.21). The adjusted treatment difference for M1 volume was −1.9 cm³ (95% CI −5.0 to 1.2; p = 0.22) and for M2 volume 0.23 cm³ (p = 0.86). In the MC that remained M1-dominant, volume change correlated positively with increased symptoms in the placebo group, whereas the correlations were negative and weak in the ZA group.

Conclusions: Zoledronic acid tended to speed up the conversion of M1-dominant into M2-dominant MC and decrease the volume of M1-dominant MC, although statistical significance was not demonstrated.

Trial registration: The registration number in is NCT01330238 and the date of registration February 11, 2011.

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Series: BMC musculoskeletal disorders
ISSN: 1471-2474
ISSN-E: 1471-2474
ISSN-L: 1471-2474
Volume: 18
Issue: 1
Article number: 274
DOI: 10.1186/s12891-017-1632-z
Type of Publication: A1 Journal article – refereed
Field of Science: 3141 Health care science
3126 Surgery, anesthesiology, intensive care, radiology
Funding: Novartis Pharma provided investigational medications for the study and supported the conduct of the trial (<10,000$). The funders played no role in study design, data collection or analysis, decision to publish, or the preparation of the manuscript.
Copyright information: © The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.