Serum Biomarkers for Connective Tissue and Basement Membrane Remodeling Are Associated with Vertebral Endplate Bone Marrow Lesions as Seen on MRI (Modic Changes)

Abstract

Vertebral endplate bone marrow lesions, visualized on magnetic resonance imaging (MRI) as Modic changes (MC), are associated with chronic low back pain (cLBP). Since guidelines recommend against routine spinal MRI for cLBP in primary care, MC may be underdiagnosed. Serum biomarkers for MC would allow early diagnosis, inform clinical care decisions, and supplement treatment monitoring. We aimed to discover biomarkers in the blood serum that correlate with MC pathophysiological processes. For this single-site cross-sectional study, we recruited 54 subjects with 38 cLBP patients and 16 volunteers without a history of LBP. All subjects completed an Oswestry Disability Index (ODI) questionnaire and 10-cm Visual Analog Score (VAS) for LBP (VASback) and leg pain. Lumbar T1-weighted and fat-saturated T2-weighted MRI were acquired at 3T and used for MC classification in each endplate. Blood serum was collected on the day of MRI. Biomarkers related to disc resorption and bone marrow fibrosis were analyzed with enzyme-linked immune-absorbent assays. The concentration of biomarkers between no MC and any type of MC (AnyMC), MC1, and MC2 were compared. The Area Under the Curve (AUC) of the Receiver Operating Characteristics were calculated for each biomarker and for bivariable biomarker models. We found that biomarkers related to type III and type IV collagen degradation and formation tended to correlate with the presence of MC (p = 0.060–0.088). The bivariable model with the highest AUC was PRO-C3 + C4M and had a moderate diagnostic value for AnyMC in cLBP patients (AUC = 0.73, specificity = 78.9%, sensitivity = 73.7%). In conclusion, serum biomarkers related to the formation and degradation of type III and type IV collagen, which are key molecules in bone marrow fibrosis, correlated with MC presence. Bone marrow fibrosis may be an important pathophysiological process in MC that should be targeted in larger biomarker and treatment studies.

Pro-fibrotic phenotype of bone marrow stromal cells in Modic type 1 changes

“…Bone marrow fibrosis is a pathophysiological important mechanism in MC1 and may have diagnostic and clinical relevance (Dudli et al, 2017;Dudli et al, 2020;Modic et al, 1988). The present study showed that BMSCs in MC1 have a profibrotic phenotype compared to BMSCs from control vertebral bone marrow from the same patient.…”

“…Ann Rheum Dis 79: 159; conference abstract; Klingberg et al, 2013]. Importantly, circulating pro-collagen type IV has been reported to be increased in peripheral blood of MC1 patients (Dudli et al, 2020). This shows that increased ECM secretion through fibrotic mechanisms in MC1 has a potential diagnostic value.…”

Macrophage migration inhibitory factor: a potential biomarker for chronic low back pain in patients with Modic changes

“…15 Biomarkers related to disc resorption and bone marrow fibrosis have been correlated with the presence of MCs. 16 A recent study comparing serum biomarkers between patients with cLBP with MCs and healthy controls reported that several cytokines were suppressed in serum among patients with MC. 17 Some studies report upregulation of cytokines in the disc in MCs, 14 18-20 but no serum biomarker is established for MCs.…”

“…All analyses were done using SPSS V.27, STATA V. 16 and the R programming language (http://www. r-project.…”

Perspectives of targeted therapy for nonspecific back pain: a review of recent publications

“…Изучались сывороточные биомаркеры повреждения соединительной ткани и ремоделирования основной мембраны, ассоциированные с повреждениями концевой пластины костного мозга, видимыми на МРТ (изменения по Modic) [29]. В исследовании участвовали 38 пациентов с хронической болью в нижней части спины и 16 здоровых добровольцев.…”