The Effect of Zoledronic Acid on Serum Biomarkers among Patients with Chronic Low Back Pain and Modic Changes in Lumbar Magnetic Resonance Imaging

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.

Download Full-text

Efficacy of zoledronic acid for chronic low back pain associated with Modic changes in magnetic resonance imaging

BMC Musculoskeletal Disorders ◽

10.1186/1471-2474-15-64 ◽

2014 ◽

Vol 15 (1) ◽

Cited By ~ 20

Author(s):

Katri Koivisto ◽

Eero Kyllönen ◽

Marianne Haapea ◽

Jaakko Niinimäki ◽

Kaj Sundqvist ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Low Back Pain ◽

Back Pain ◽

Zoledronic Acid ◽

Magnetic Resonance ◽

Chronic Low Back Pain ◽

Modic Changes ◽

Low Back ◽

Resonance Imaging

Download Full-text

Efficacy of antibiotic treatment in patients with chronic low back pain and Modic changes (the AIM study): double blind, randomised, placebo controlled, multicentre trial

BMJ ◽

10.1136/bmj.l5654 ◽

2019 ◽

pp. l5654 ◽

Cited By ~ 13

Author(s):

Lars Christian Haugli Bråten ◽

Mads Peder Rolfsen ◽

Ansgar Espeland ◽

Monica Wigemyr ◽

Jörg Aßmus ◽

...

Keyword(s):

Low Back Pain ◽

Back Pain ◽

Antibiotic Treatment ◽

Disc Herniation ◽

Chronic Low Back Pain ◽

Modic Changes ◽

Low Back ◽

Double Blind ◽

The Difference ◽

One Year

Abstract Objective To assess the efficacy of three months of antibiotic treatment compared with placebo in patients with chronic low back pain, previous disc herniation, and vertebral endplate changes (Modic changes). Design Double blind, parallel group, placebo controlled, multicentre trial. Setting Hospital outpatient clinics at six hospitals in Norway. Participants 180 patients with chronic low back pain, previous disc herniation, and type 1 (n=118) or type 2 (n=62) Modic changes enrolled from June 2015 to September 2017. Interventions Patients were randomised to three months of oral treatment with either 750 mg amoxicillin or placebo three times daily. The allocation sequence was concealed by using a computer generated number on the prescription. Main outcome measures The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (range 0-24) at one year follow-up in the intention to treat population. The minimal clinically important between group difference in mean RMDQ score was predefined as 4. Results In the primary analysis of the total cohort at one year, the difference in the mean RMDQ score between the amoxicillin group and the placebo group was −1.6 (95% confidence interval −3.1 to 0.0, P=0.04). In the secondary analysis, the difference in the mean RMDQ score between the groups was −2.3 (−4.2 to−0.4, P=0.02) for patients with type 1 Modic changes and −0.1 (−2.7 to 2.6, P=0.95) for patients with type 2 Modic changes. Fifty patients (56%) in the amoxicillin group experienced at least one drug related adverse event compared with 31 (34%) in the placebo group. Conclusions In this study on patients with chronic low back pain and Modic changes at the level of a previous disc herniation, three months of treatment with amoxicillin did not provide a clinically important benefit compared with placebo. Secondary analyses and sensitivity analyses supported this finding. Therefore, our results do not support the use of antibiotic treatment for chronic low back pain and Modic changes. Trial registration ClinicalTrials.gov NCT02323412 .

Download Full-text

Investigating a Possible Link between MRI Findings of Lumbar Disc Degeneration and Modic Changes in the Patients with Chronic Low Back Pain

Orthopedic Research Online Journal ◽

10.31031/oproj.2018.04.000598 ◽

2018 ◽

Vol 4 (5) ◽

Author(s):

Farzad Omidi Kashani

Keyword(s):

Low Back Pain ◽

Back Pain ◽

Disc Degeneration ◽

Chronic Low Back Pain ◽

Lumbar Disc ◽

Modic Changes ◽

Low Back ◽

Lumbar Disc Degeneration ◽

Mri Findings

Download Full-text

The effect of infliximab in patients with chronic low back pain and Modic changes (the BackToBasic study): study protocol of a randomized, double blind, placebo-controlled, multicenter trial

BMC Musculoskeletal Disorders ◽

10.1186/s12891-020-03720-5 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Elisabeth Gjefsen ◽

Lars Christian Haugli Bråten ◽

Guro Løvik Goll ◽

Monica Wigemyr ◽

Nils Bolstad ◽

...

Keyword(s):

Low Back Pain ◽

Back Pain ◽

Chronic Low Back Pain ◽

Treatment Strategy ◽

Treatment Options ◽

Modic Changes ◽

Low Back ◽

Double Blind ◽

Link Type

Abstract Background Low back pain is common and a significant number of patients experience chronic low back pain. Current treatment options offer small to moderate effects. Patients with vertebral bone marrow lesions visualized as Modic changes on magnetic resonance imaging may represent a subgroup within the low back pain population. There is evidence for inflammatory mediators being involved in development of Modic changes; hence, suppression of inflammation could be a treatment strategy for these patients. This study examines the effect of anti-inflammatory treatment with the TNF-α inhibitor infliximab in patients with chronic low back pain and Modic changes. Methods/design The BackToBasic trial is a multicenter, double blind, randomized controlled trial conducted at six hospitals in Norway, comparing intravenous infusions with infliximab with placebo. One hundred twenty-six patients aged 18–65 with chronic low back pain and type 1 Modic changes will be recruited from secondary care outpatients’ clinics. The primary outcome is back pain-specific disability at day 154 (5 months). The study is designed to detect a difference in change of 10 (SD 18) in the Oswestry Disability Index at day 154/ 5 months. The study also aims to refine MRI-assessment, investigate safety and cost-effectiveness and explore the underlying biological mechanisms of Modic changes. Discussion Finding treatments that target underlying mechanisms could pose new treatment options for patients with low back pain. Suppression of inflammation could be a treatment strategy for patients with low back pain and Modic changes. This paper presents the design of the BackToBasic study, where we will assess the effect of an anti-inflammatory treatment versus placebo in patients with chronic low back pain and type 1 Modic changes. The study is registered at ClinicalTrials.gov under the identifier NCT03704363. The EudraCT Number: 2017–004861-29.

Download Full-text