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

• DOI: 10.3390/diagnostics9040212
• Publication Date: 2019-12-05T08:16:36Z
• Authors: Katri Koivisto; Jaro Karppinen; Marianne Haapea; Jyri Järvinen; Eero Kyllönen; Osmo Tervonen; Jaakko Niinimäki; Mauro Alini; Jeffrey Lotz; Stefan Dudli; Dino Samartzis; Juha Risteli; Marja-Leena Majuri; Harri Alenius; Sibylle Grad
• Keywords: Modic change; Clinical Sciences; Clinical Trials and Supportive Activities; serum biomarkers; 610; 610 Medicine & health; Clinical sciences; 1308 Clinical Biochemistry; Article; zoledronic acid; 03 medical and health sciences; 0302 clinical medicine; Clinical Research; randomized trial; magnetic resonance imaging; Biomedical and Clinical Sciences; Pain Research; 10051 Rheumatology Clinic and Institute of Physical Medicine; Evaluation of treatments and therapeutic interventions; serum biomarkersm magnetic resonance imaging; 6.1 Pharmaceuticals; Musculoskeletal; chronic low back pain; Chronic Pain

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.