Jaro Karppinen1,2,3, Katri Koivisto1, Jukka Ketola1, Marianne Haapea1,2,4, Markus Paananen1, Karl-Heinz Herzig1,5,6, Mauro Alini7, Jeffrey Lotz8, Stefan Dudli9, Dino Samartzis10,11, Juha Risteli12, Marja-Leena Majuri1, Harri Alenius13, Eero Kyllönen1, Jyri Järvinen4, Jaakko Niinimäki1,4, Sibylle Grad7. 1. Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland. 2. Center for Life Course Health Research, University of Oulu, Oulu, Finland. 3. Finnish Institute of Occupational Health, Oulu, Finland. 4. Research Unit of Medical Imaging, Physics and Technology, Faculty of Medicine, University of Oulu, Oulu, Finland. 5. Research Unit of Biomedicine and Biocenter Oulu, Department of Physiology, University of Oulu, Oulu, Finland. 6. Department of Gastroenterology and Metabolism, Poznan University of Medical Sciences, Poznan, Poland. 7. AO Research Institute, Davos, Switzerland. 8. Department of Orthopaedic Surgery, University of California San Francisco, San Francisco, USA. 9. Center of Experimental Rheumatology, University Hospital Zurich, Zurich, Switzerland. 10. Department of Orthopaedic Surgery, RUSH University Medical Center, Suite 204-G, 1611 W. Harrison Street, Orthopaedic BuildingChicago, IL, 60612, USA. dino_samartzis@rush.edu. 11. International Spine Research and Innovation Initiative, RUSH University, Chicago, USA. dino_samartzis@rush.edu. 12. Northern Finland Laboratory Centre NordLab, Oulu University Hospital, Oulu, Finland. 13. Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 MCpatients, irrespective of MC type or size, with CLBP compared with asymptomatic controls.
Entities:
Keywords:
Biomarkers; Chronic low back pain; Magnetic resonance imaging; Modic change; Serum; Zoledronic acid
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