INTRODUCTION: Intervertebral disc degeneration (DD) is an age-related phenomenon and a major risk factor for low back pain (LBP). However, it is believed that not all LBP is discogenic in origin and that “vertebrogenic” causation of pain may be present and have unique signatures. Modic changes (MC) are pathological vertebral endplate and bone marrow changes visible on magnetic resonance imaging (MRI) that are highly associated with LBP and increased age. Our team had previously identified circulating blood proinflammatory cytokines that were related to DD and severity of DD as well as a specific blood biomarkers that were significantly elevated between MC and asymptomatic subjects. The following NIH-funded study aimed to determine the existence and expression of specific proinflammatory cytokines, chemokines and growth factors in circulating blood between “symptomatic patients” who presented to clinic with or without MC of the lumbar spine on MRI.
Methods: A prospective study was performed at a single center. Fasting blood samples were collected from 25 patients with lumbar MC and 25 with no-MC who had undergone spinal fusion or microdiscectomy. An 80-plex panel and CCL5/RANTES were used to assess serum cytokine concentrations. No patient had any deformity, tumor, infection of inflammatory condition related to the spine. Preoperative T2/T1-weighted axial and sagittal MRI of L1-S1 was obtained of all subjects to determine the presence of MC. Subject demographics were also collected and analysed.
Results At the time of this study, 33 subjects were analysed (n=13 MC, n=18 no-MC). No significant differences were found in age, sex, or BMI between the two groups (p>0.05). The study identified several significant blood biomarkers in MC patients, including elevated levels of C-X-C Motif Chemokine Ligand 5 (CXCL5, p<0.05), C-C Motif Chemokine Ligand 5 (CCL5, p<0.01), while Macrophage Migration Inhibitory Factor (MIF) was downregulated (p<0.01). Additionally, two other biomarkers, Pentraxin 3 (PTX3, p<0.06) and Galectin-3 (Gal-3, p<0.07), showed trends toward significance. Moreover, as expected, MC patients exhibited significantly higher levels of disc degeneration (p<0.05).
Discussion: This is the “first” study, to our knowledge, that has identified specific and significant circulating blood biomarkers to be related to symptomatic patients with MC of the lumbar spine. Specifically, MIF, CXCL5 and CCL5 protein levels were found to be significantly different in MC patients as compared to non-MC subjects. This study further “replicated” CCL5 as a viable biomarker of MC that was previously noted by the authors representing another cohort. Although our recent findings are preliminary and require larger-studies and validation, our work provides evidence that symptomatic MC patients may exhibit unique inflammatory signatures easily identifiable in the blood. Such knowledge can expand on the pathomechanisms of MC, and also lend credence to more refined classification and subphenotyping of MC patients that could also have direct impact on future precision-based spine care models of management and predictive modelling.