The effect of obesity upon the lumbar spine

<p>Back pain is a massive global public health problem with multiple contributing factors including obesity. Obesity is thought to be linked to back pain through mechanical factors. However, obesity also causes a systemic low-grade inflammatory milieu. This would suggest a possible biochemica...

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Main Author: Segar, A
Other Authors: Urban, J
Format: Thesis
Language:English
Published: 2015
Subjects:
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author Segar, A
author2 Urban, J
author_facet Urban, J
Segar, A
author_sort Segar, A
collection OXFORD
description <p>Back pain is a massive global public health problem with multiple contributing factors including obesity. Obesity is thought to be linked to back pain through mechanical factors. However, obesity also causes a systemic low-grade inflammatory milieu. This would suggest a possible biochemical link between obesity, intervertebral disc degeneration, and back pain. Furthermore, the relationship between obesity and the clinical presentation of spine patients is unclear. This thesis aims to examine the effect of and relationship between obesity, the intervertebral discs, and back pain from biochemical, clinical, and epidemiological perspectives</p> <p>In this thesis, an <em>in vitro</em> study assessed the effect of leptin, a fat-specific cytokine, upon the intervertebral disc. The bovine intervertebral disc was used as a model in a cell culture system. An <em>ex vivo</em> study examined leptin and pro-inflammatory cytokines produced by paraspinal adipose tissue taken during routine surgical procedures from spinal patients. Plasma taken from patients presenting with low back pain was analysed by mass spectrometry and multiplex immunoassay to identify possible protein biomarkers. At an epidemiological level, statistical modelling of the Genodisc patient population was conducted. This was a pan-European study of 2636 patients presenting to tertiary spinal units. Analyses were performed to examine relationships between obesity, quantified by body mass index (BMI), and pain, clinical diagnosis, and spinal degeneration identified on magnetic resonance imaging (MRI).</p> <p>Leptin was shown to increase the production of and expression of degradative and pain-generating molecules by disc cells. A pro-inflammatory environment, especially IL-6, potentiated this response. Leptin and pro-inflammatory cytokines produced by paraspinal fat were unrelated to clinical symptoms. However, levels of the pro-inflammatory cytokines, TNF-α and IL-6, were raised in the plasma of patients with greater pain or those with spinal stenosis. Furthermore, clusterin and complement were identified, by mass spectrometry, as potential biomarkers for spine patients. Epidemiological analyses revealed that obesity was associated with greater back pain, although the magnitude of this association was small. Similarly, obesity was associated with a diagnosis of spinal stenosis. Finally, increased BMI was found to be an independent predictor of disc degeneration, spinal stenosis, and disc herniation on MRI.</p> <p>In summary, this thesis has furthered the clinical understanding of lumbar spine pathology and back pain. It will provide clinicians with a better framework to assess spine patients. These results show that obesity is associated with lumbar spine degeneration and pain. Leptin could be a factor mediating this relationship. Further studies should concentrate on clarifying the mechanism of action of leptin upon the intervertebral disc and assessing the longitudinal effect of obesity upon the lumbar spine.</p>
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spelling oxford-uuid:0db5f091-0f6f-4686-957e-22c5390232b02024-12-01T12:10:45ZThe effect of obesity upon the lumbar spineThesishttp://purl.org/coar/resource_type/c_db06uuid:0db5f091-0f6f-4686-957e-22c5390232b0Medical SciencesOrthopaedicsSurgeryEpidemiologyEnglishOxford University Research Archive - Valet2015Segar, AUrban, JFairbank, JJudge, A<p>Back pain is a massive global public health problem with multiple contributing factors including obesity. Obesity is thought to be linked to back pain through mechanical factors. However, obesity also causes a systemic low-grade inflammatory milieu. This would suggest a possible biochemical link between obesity, intervertebral disc degeneration, and back pain. Furthermore, the relationship between obesity and the clinical presentation of spine patients is unclear. This thesis aims to examine the effect of and relationship between obesity, the intervertebral discs, and back pain from biochemical, clinical, and epidemiological perspectives</p> <p>In this thesis, an <em>in vitro</em> study assessed the effect of leptin, a fat-specific cytokine, upon the intervertebral disc. The bovine intervertebral disc was used as a model in a cell culture system. An <em>ex vivo</em> study examined leptin and pro-inflammatory cytokines produced by paraspinal adipose tissue taken during routine surgical procedures from spinal patients. Plasma taken from patients presenting with low back pain was analysed by mass spectrometry and multiplex immunoassay to identify possible protein biomarkers. At an epidemiological level, statistical modelling of the Genodisc patient population was conducted. This was a pan-European study of 2636 patients presenting to tertiary spinal units. Analyses were performed to examine relationships between obesity, quantified by body mass index (BMI), and pain, clinical diagnosis, and spinal degeneration identified on magnetic resonance imaging (MRI).</p> <p>Leptin was shown to increase the production of and expression of degradative and pain-generating molecules by disc cells. A pro-inflammatory environment, especially IL-6, potentiated this response. Leptin and pro-inflammatory cytokines produced by paraspinal fat were unrelated to clinical symptoms. However, levels of the pro-inflammatory cytokines, TNF-α and IL-6, were raised in the plasma of patients with greater pain or those with spinal stenosis. Furthermore, clusterin and complement were identified, by mass spectrometry, as potential biomarkers for spine patients. Epidemiological analyses revealed that obesity was associated with greater back pain, although the magnitude of this association was small. Similarly, obesity was associated with a diagnosis of spinal stenosis. Finally, increased BMI was found to be an independent predictor of disc degeneration, spinal stenosis, and disc herniation on MRI.</p> <p>In summary, this thesis has furthered the clinical understanding of lumbar spine pathology and back pain. It will provide clinicians with a better framework to assess spine patients. These results show that obesity is associated with lumbar spine degeneration and pain. Leptin could be a factor mediating this relationship. Further studies should concentrate on clarifying the mechanism of action of leptin upon the intervertebral disc and assessing the longitudinal effect of obesity upon the lumbar spine.</p>
spellingShingle Medical Sciences
Orthopaedics
Surgery
Epidemiology
Segar, A
The effect of obesity upon the lumbar spine
title The effect of obesity upon the lumbar spine
title_full The effect of obesity upon the lumbar spine
title_fullStr The effect of obesity upon the lumbar spine
title_full_unstemmed The effect of obesity upon the lumbar spine
title_short The effect of obesity upon the lumbar spine
title_sort effect of obesity upon the lumbar spine
topic Medical Sciences
Orthopaedics
Surgery
Epidemiology
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