Lumbar Modic change (MC) can serve as a diagnostic marker as well as an independent source of chronic low back pain (CLBP). This study aimed to test for the existence of serum biomarkers in CLBP patients with MC.
Age- and sex-matched CLBP patients with confirmed MC on lumbar MRI (n = 40) and pain-free controls (n = 40) were assessed. MC was classified into M1, predominating M1, predominating M2 and M2. MC volumes were calculated. Fasting blood samples were assessed for inflammatory mediators, signalling molecules, growth factors and bone turnover markers. Serum concentrations of 46 biomarkers were measured.
Median concentrations of interleukin (IL)-15 (p < 0.001), IL-8 (p < 0.001), tumour necrosis factor (TNF)-alpha (p < 0.001), Eotaxin-1 (p < 0.05), Eotaxin-3 (p < 0.001), monocyte chemotactic protein (MCP)-1 (p < 0.05), macrophage inflammatory protein (MIP)-1alpha (p < 0.01), TEK receptor tyrosine kinase (Tie)-2 (p < 0.001), vascular cell adhesion molecule (VCAM)-1 (p < 0.001), RANTES (p < 0.001), C telopeptide of type I collagen (CTX)-1 (p < 0.001), vascular endothelial growth factor (VEGF)-C (p < 0.001), VEGF-D (p < 0.05), fms-related tyrosine kinase (Flt)-1 (p < 0.01) and intercellular adhesion molecule (ICAM)-1 (p < 0.01) were significantly higher among controls. IL-1sRII (23.2 vs. 15.5 ng/ml, p < 0.001) and hepatocyte growth factor (HGF)-1 (169 vs. 105 pg/ml, p < 0.01) concentrations were significantly higher among patients. Type or volume of MC was not associated with biomarker concentrations.
This is the first study to assess the blood serum biomarker profile in individuals with CLBP with MC. Several biomarkers were suppressed, while two markers (IL-1sRII and HGF) were elevated among MC patients, irrespective of MC type or size, with CLBP compared with asymptomatic controls.
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Hartvigsen J, Hancock MJ, Kongsted A et al (2018) What low back pain is and why we need to pay attention. Lancet 391:2356–2367
Hoy D, March L, Brooks P et al (2014) The global burden of low back pain: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis 73:968–974
de Roos A, Kressel H, Spritzer C et al (1987) MR imaging of marrow changes adjacent to end plates in degenerative lumbar disk disease. AJR Am J Roentgenol 149:531–534
Modic MT, Masaryk TJ, Ross JS et al (1988) Imaging of degenerative disk disease. Radiology 168:177–186
Modic MT, Steinberg PM, Ross JS et al (1988) Degenerative disk disease: assessment of changes in vertebral body marrow with MR imaging. Radiology 166:193–199
Perilli E, Parkinson IH, Truong LH et al (2015) Modic (endplate) changes in the lumbar spine: bone micro-architecture and remodelling. Eur Spine J 24:1926–1934
Jarvik JJ, Hollingworth W, Heagerty P et al (2001) The Longitudinal Assessment of Imaging and Disability of the Back (LAIDBack) Study: baseline data. Spine. 26:1158–1166
Kjaer P, Leboeuf-Yde C, Korsholm L et al (2005) Magnetic resonance imaging and low back pain in adults: a diagnostic imaging study of 40-year-old men and women. Spine. 30:1173–1180
Kuisma M, Karppinen J, Niinimaki J et al (2007) Modic changes in endplates of lumbar vertebral bodies: prevalence and association with low back and sciatic pain among middle-aged male workers. Spine. 32:1116–1122
Maatta JH, Karppinen J, Paananen M et al (2016) Refined Phenotyping of Modic Changes: Imaging Biomarkers of Prolonged Severe Low Back Pain and Disability. Medicine (Baltimore) 95:e3495
Maatta JH, Wadge S, MacGregor A et al (2015) ISSLS Prize Winner: Vertebral Endplate (Modic) Change is an Independent Risk Factor for Episodes of Severe and Disabling Low Back Pain. Spine. 40:1187–1193
Mok FP, Samartzis D, Karppinen J et al (2016) Modic changes of the lumbar spine: prevalence, risk factors and association with disc degeneration and low back pain in a large-scale population-based cohort. Spine J 16:32–41
Teraguchi M, Yoshimura N, Hashizume H et al (2015) The association of combination of disc degeneration, end plate signal change and Schmorl node with low back pain in a large population study: the Wakayama Spine Study. Spine J 15:622–628
Tonosu J, Oka H, Higashikawa A et al (2017) The associations between magnetic resonance imaging findings and low back pain: A 10-year longitudinal analysis. PLoS ONE 12:e0188057
Albert HB, Kjaer P, Jensen TS et al (2008) Modic changes, possible causes and relation to low back pain. Med Hypotheses 70:361–368
Jarvinen J, Karppinen J, Niinimaki J et al (2015) Association between changes in lumbar Modic changes and low back symptoms over a two-year period. BMC Musculoskelet Disord 16:98
Jensen OK, Nielsen CV, Sorensen JS et al (2014) Type 1 Modic changes was a significant risk factor for 1-year outcome in sick-listed low back pain patients: a nested cohort study using magnetic resonance imaging of the lumbar spine. Spine J 14:2568–2581
Jensen TS, Karppinen J, Sorensen JS et al (2008) Vertebral endplate signal changes (Modic change): a systematic literature review of prevalence and association with non-specific low back pain. Eur Spine J 17:1407–1422
Schistad EI, Espeland A, Rygh LJ et al (2014) The association between Modic changes and pain during 1-year follow-up in patients with lumbar radicular pain. Skeletal Radiol 43:1271–1279
Biomarkers and surrogate endpoints (2001) preferred definitions and conceptual framework. Clin Pharmacol Ther 69:89–95
Attur M, Krasnokutsky-Samuels S, Samuels J et al (2013) Prognostic biomarkers in osteoarthritis. Curr Opin Rheumatol 25:136–144
Hosnijeh FS, Runhaar J, van Meurs JB et al (2015) Biomarkers for osteoarthritis: Can they be used for risk assessment? A systematic review Maturitas 82:36–49
Lotz M, Martel-Pelletier J, Christiansen C et al (2013) Value of biomarkers in osteoarthritis: current status and perspectives. Ann Rheum Dis 72:1756–1763
Trouw LA, Mahler M (2012) Closing the serological gap: promising novel biomarkers for the early diagnosis of rheumatoid arthritis. Autoimmun Rev 12:318–322
Livshits G, Kalinkovich A (2018) Hierarchical, imbalanced pro-inflammatory cytokine networks govern the pathogenesis of chronic arthropathies. Osteoarthritis Cartilage 26:7–17
Mc Ardle A, Flatley B, Pennington SR et al (2015) Early biomarkers of joint damage in rheumatoid and psoriatic arthritis. Arthritis Res Ther 17:141
Sanchez C, Bay-Jensen AC, Pap T et al (2017) Chondrocyte secretome: a source of novel insights and exploratory biomarkers of osteoarthritis. Osteoarthritis Cartilage 25:1199–1209
Rannou F, Ouanes W, Boutron I et al (2007) High-sensitivity C-reactive protein in chronic low back pain with vertebral end-plate Modic signal changes. Arthritis Rheum 57:1311–1315
Koivisto K, Kyllonen E, Haapea M et al (2014) Efficacy of zoledronic acid for chronic low back pain associated with Modic changes in magnetic resonance imaging. BMC Musculoskelet Disord 15:64
Koivisto K, Jarvinen J, Karppinen J et al (2017) The effect of zoledronic acid on type and volume of Modic changes among patients with low back pain. BMC Musculoskelet Disord 18:274
Dudli S, Fields AJ, Samartzis D et al (2016) Pathobiology of Modic changes. Eur Spine J 25:3723–3734
Kuisma M, Karppinen J, Haapea M et al (2009) Modic changes in vertebral endplates: a comparison of MR imaging and multislice CT. Skeletal Radiol 38:141–147
Dudli S, Liebenberg E, Magnitsky S et al (2018) Modic type 1 change is an autoimmune response that requires a proinflammatory milieu provided by the “Modic disc.” Spine J 18:831–844
Dudli S, Sing DC, Hu SS et al (2017) ISSLS PRIZE IN BASIC SCIENCE 2017: Intervertebral disc/bone marrow cross-talk with Modic changes. Eur Spine J 26:1362–1373
Schroeder GD, Markova DZ, Koerner JD et al (2017) Are Modic changes associated with intervertebral disc cytokine profiles? Spine J 17:129–134
Torkki M, Majuri ML, Wolff H et al (2016) Osteoclast activators are elevated in intervertebral disks with Modic changes among patients operated for herniated nucleus pulposus. Eur Spine J 25:207–216
Rechardt M, Shiri R, Matikainen S et al (2011) Soluble IL-1RII and IL-18 are associated with incipient upper extremity soft tissue disorders. Cytokine 54:149–153
Klyne DM, Barbe MF, van den Hoorn W et al (2018) ISSLS PRIZE IN CLINICAL SCIENCE 2018: longitudinal analysis of inflammatory, psychological and sleep-related factors following an acute low back pain episode-the good, the bad and the ugly. Eur Spine J 27:763–777
Coudriet GM, He J, Trucco M et al (2010) Hepatocyte growth factor modulates interleukin-6 production in bone marrow derived macrophages: implications for inflammatory mediated diseases. PLoS ONE 5:e15384
Molnarfi N, Benkhoucha M, Funakoshi H et al (2015) Hepatocyte growth factor: A regulator of inflammation and autoimmunity. Autoimmun Rev 14:293–303
Capossela S, Pavlicek D, Bertolo A et al (2018) Unexpectedly decreased plasma cytokines in patients with chronic back pain. J Pain Res 11:1191–1198
Rogers EL, Reynard LN, Loughlin J (2015) The role of inflammation-related genes in osteoarthritis. Osteoarthritis Cartilage 23:1933–1938
Hou X, Pei F (2015) Estradiol Inhibits Cytokine-Induced Expression of VCAM-1 and ICAM-1 in Cultured Human Endothelial Cells Via AMPK/PPARalpha Activation. Cell Biochem Biophys 72:709–717
Ding L, Teng X, Fan S et al (2015) The Association Between Modic Changes of Lumbar Endplates and Spontaneous Absorption of Herniated Intervertebral Discs. Cell Biochem Biophys 71:1357–1363
McFadyen JD, Kiefer J, Braig D et al (2018) Dissociation of C-Reactive Protein Localizes and Amplifies Inflammation: Evidence for a Direct Biological Role of C-Reactive Protein and Its Conformational Changes. Front Immunol 9:1351
Pepys MB, Hirschfield GM (2003) C-reactive protein: a critical update. J Clin Invest 111:1805–1812
Reveille JD (2015) Biomarkers for diagnosis, monitoring of progression and treatment responses in ankylosing spondylitis and axial spondyloarthritis. Clin Rheumatol 34:1009–1018
Kawaguchi Y, Nakano M, Yasuda T et al (2017) Serum biomarkers in patients with ossification of the posterior longitudinal ligament (OPLL): Inflammation in OPLL. PLoS ONE 12:e0174881
Shiri R, Karppinen J, Leino-Arjas P et al (2007) Cardiovascular and lifestyle risk factors in lumbar radicular pain or clinically defined sciatica: a systematic review. Eur Spine J 16:2043–2054
Galic S, Oakhill JS, Steinberg GR (2010) Adipose tissue as an endocrine organ. Mol Cell Endocrinol 316:129–139
Grad S, Bow C, Karppinen J et al (2016) Systemic blood plasma CCL5 and CXCL6: Potential biomarkers for human lumbar disc degeneration. Eur Cell Mater 31:1–10
Khan AN, Jacobsen HE, Khan J et al (2017) Inflammatory biomarkers of low back pain and disc degeneration: a review. Ann N Y Acad Sci 1410:68–84
Bendix T, Sorensen JS, Henriksson GAC et al (2012) Lumbar modic changes-a comparison between findings at low- and high-field magnetic resonance imaging. Spine. 37:1756–1762
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Karppinen, J., Koivisto, K., Ketola, J. et al. Serum biomarkers for Modic changes in patients with chronic low back pain. Eur Spine J 30, 1018–1027 (2021). https://doi.org/10.1007/s00586-020-06713-z
- Magnetic resonance imaging
- Modic change
- Zoledronic acid
- Chronic low back pain