RESEARCH REPORT 395. Ten year follow-up study of MR imaging of the lumbar spine HSE

Transcription

1 HSE Health & Safety Executive Ten year follow-up study of MR imaging of the lumbar spine Prepared by the University of Liverpool and University of Manchester for the Health and Safety Executive 2005 RESEARCH REPORT 395

2 HSE Health & Safety Executive Ten year follow-up study of MR imaging of the lumbar spine *Professor Neil Roberts *Professor Graeme H Whitehouse Professor Gary J Macfarlane *Dr Niamh M Redmond BSc PhD Mrs Ann C Papageorgiou *Magnetic Resonance Image Analysis Research Centre (MARIARC) Pembroke Place University of Liverpool Liverpool L69 3BX Unit of Chronic Disease Epidemiology School of Epidemiology & Health Sciences University of Manchester Manchester M13 9PL This research study was conducted to establish whether a relationship existed between occupational, lifestyle factors, MRI-diagnosed pathology and low back pain (LBP) over a 10 year period. Epidemiological risk factors for the presence, onset and worsening of LBP over the follow-up period and risk factors for the onset of pathology in the spine were also investigated. 104 subjects were followed up from an original study into the role of MR imaging in the evaluation of LBP. LBP history, occupational and lifestyle characteristics were obtained by questionnaire and 70 subjects underwent successful MRI scans of the lumbar spine. At follow-up, nearly half of all subjects reported having LBP on a monthly basis and MRI-diagnosed pathological features were extensive across the spine particularly at the lower lumbar spinal levels. 19% of subjects developed new-onset pain from none previously, whilst a quarter of subjects pain worsened over the study period. 22% of subjects developed onset of pathology in the spine from none previously. Few factors emerged from multiple logistic regression analysis as being significant independent predictors of frequent, onset and worsening LBP. No risk factors could be established for the onset of disc degeneration or herniation in the spine. Although subjects experienced an increase in pathological features with increasing LBP occurrence, no link could be established to suggest causal factors to the development of new pain or pathology. This supports the idea that pathological change and nonspecific LBP experience in workers is likely to be co-incidental. This report and the work it describes were funded by the Health and Safety Executive (HSE). Its contents, including any opinions and/or conclusions expressed, are those of the authors alone and do not necessarily reflect HSE policy. HSE BOOKS

3 Crown copyright 2005 First published 2005 All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means (electronic, mechanical, photocopying, recording or otherwise) without the prior written permission of the copyright owner. Applications for reproduction should be made in writing to: Licensing Division, Her Majesty's Stationery Office, St Clements House, 2-16 Colegate, Norwich NR3 1BQ or by to hmsolicensing@cabinet-office.x.gsi.gov.uk ii

4 ACKNOWLEDGEMENTS The authors would like to thank the volunteers who kindly returned to participate in this study, over 10 years since their involvement in the original study. Without their continued contribution this study would not have been possible. A particular mention should be made with regard to the contribution of Mrs. Ann Papageorgiou for tracing the study subjects so effectively and to Prof. Gary Macfarlane for his valuable advice on formulating the follow-up questionnaire and epidemiological statistical analysis. Finally, the authors are most grateful to Mrs. Jane Chance (Research Nurse) who helped considerably to recruit the volunteers for MRI scanning and to the team of Radiographers working at MARIARC who conducted the MRI scanning of the volunteers. iii

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6 CONTENTS ACKNOWLEDGEMENTS iii CONTENTS iv EXECUTIVE SUMMARY vi 1 INTRODUCTION Background to the study Aims and Objectives 2 2 METHODS Tracing original subjects Low back pain questionnaire MRI scanning protocol Pathology classification and assessment baseline study data study data Statistical Analysis 9 3 RESULTS Analysis of responders Responders original 1988 baseline data Analysis of contributing factors to low back pain Follow-up data Analysis of contributing factors to present low back pain Changes over the study period ( ) Establishing predictors for future low back pain Establishing predictors for future pathology 35 v

7 4 DISCUSSION Limitations of the study Relationship to other findings Interpretation of the findings Implications of the study Further work 43 5 CONCLUSIONS 44 6 REFERENCES 45 vi

8 EXECUTIVE SUMMARY This research study stemmed from an original HSE study in 1988 which investigated the role of MR imaging of the lumbar spine in the evaluation of low back pain (LBP) in a cohort of 149 male workers (Savage et al., 1997). The original study could not clearly identify a relationship between age, occupation, MRI-diagnosed pathological features and LBP. Over 10 years later, 104 of the original subjects were traced and participated in this follow-up study to further investigate whether a relationship existed between occupational, lifestyle factors, MRIdiagnosed pathology and LBP over time. Previous studies have produced contradicting results with the longest studies so far (Boos et al, 2000, Borenstein et al., 2001) establishing weak trends between occupational characteristics, lumbar spine pathology and non-specific LBP. However, these studies were small in number and the length of follow-up time was not sufficient for any change in pathology to occur that might account for increased LBP frequency. This study s intention was to address these temporal issues in a larger cohort of occupational men. The main aim of the follow-up study was to further investigate whether a relationship existed between occupational, lifestyle factors, MRI-diagnosed pathology and LBP over time. Two further objectives were to investigate whether epidemiological risk factors for the presence, onset and worsening of LBP over the follow-up period and risk factors for the onset of pathology in the spine existed. 104 of the original subjects returned to the study with completed questionnaires on LBP history, occupational and lifestyle characteristics. 70 subjects underwent successful MRI scans of the lumbar spine. The 104 subjects original data was analysed to establish whether any bias has been introduced due to the nature of the subjects returning to the study. There was no indication of bias with regard to subject demographics, pathology, the relationships investigated in the original study or LBP frequency. In addition, no differences were established between responders to the follow-up study and non-responders. The follow-up questionnaire revealed that 58% of subjects were still working and of those, 93% of subjects longest occupation was the occupation they had been involved in during the original study. 45% of subjects reported having low back pain on a monthly basis whilst 15% reported never experiencing LBP ever. In the follow-up data, a significant relationship was found between longest occupation and self-reported present LBP status (Kruskal-Wallis, p=0.0004) with 65% of subjects whose longest occupation was a manual one reporting LBP on a monthly basis. 32% of subjects had been to see their GP or other health care professional about their pain. The majority of these (81%) were experiencing pain on a monthly basis. 12% of subjects scored high on the GHQ-12 index indicating severe psychological distress. Subjects with monthly pain scored significantly higher on this index than subjects with less or no pain (1-way ANOVA, p=0.025). Follow-up MRI-diagnosed pathology was extensive across the spine particularly at the L4/L5 and L5/S1 disc levels. Disc degeneration was the most prevalent pathological feature noted with a quarter of all discs affected by degeneration. Many subjects presented with multiple pathologies across the spine particularly at the lower disc levels, the most common being a combination of disc degeneration and herniation. Three-quarters of subjects with one pathology at the L5/S1 disc level presented with at least another pathological feature at that level. vii

9 Over the study period, 19% of subjects developed new-onset pain from none previously, whilst 25% of subject s pain worsened in frequency over the study period. Few subject s pain had diminished over the 10 years. Many subjects experience of pain had not changed since 1988 even though there was a general trend of increasing pain frequency. 45% of subjects experienced pain on a monthly basis compared to 29% in the original study. 22% of subjects developed new onset of pathology in the spine from none previously but few subjects pathology worsened in severity. A number of normal discs had herniated since the original study from normal levels particularly at L4/L5 and L5/S1 disc levels. Disc degeneration continued to affect many previously normal discs. Onset of nerve root compression occurred mainly at the L4/L5 and L5/S1 levels in line with those spinal levels affected by new onset herniation. A quarter of all subjects who developed onset of herniation at the L5/S1 level developed onset of nerve root compression. Univariate and multivariate logistic regression analysis was used to establish predictors of frequent, onset and worsening LBP. Although many factors emerged as significant on a univariate basis, very few remained as independent predictors when entered into the multivariate analysis. The strongest predictor for frequent pain was a high score on the GHQ-12 index (*OR 7.3, 95, CI ). Having had a L5/S1degenerated disc at baseline was also predictive of frequent pain but this just reached significance (OR 6.2, CI ). Increasing number of years in subjects longest occupation was a significant predictor for worsening pain in those subjects that had pain at the start of the study (OR 1.3, CI ). Also, for these subjects, belonging to the older age group (> 44yrs) somewhat decreased the risk of worsening pain occurring over the study period (OR 0.3, CI ). Onset of a compressed nerve root at the L4/L5 disc level was shown to be associated independently with new onset pain (OR 9.4, CI ), although the strength of this association was weak with only 16% of the variation for development of new pain being explained by this factor. No risk factors could be established for the onset of disc degeneration or disc herniation when previous degeneration and herniation were controlled for respectively. Involvement in heavy physical work came close to significance as being an independent risk factor for onset of disc herniation in the spine (OR 3.3, CI ). This study had many strengths notably the long duration of follow-up that had been achieved. The ability to assess pain status migration objectively was a benefit, reducing bias that may have potentially been introduced by the subjects via the questionnaire. The results agreed with much of the scientific literature with regard to the prevalence of pain for this age group of subjects. Surprisingly fewer occupational factors emerged as significantly related to pain or pathology than would have been expected, particularly considering the long duration of follow-up. Overall, the associations found supported previous work than psychosocial factors were more helpful for predicting frequent pain occurrence than MRIdiagnosed pathological features. Even though onset of neural compromise was shown to be associated with onset of pain, this was not a statistically reliable enough result to be diagnostically relevant. Overall, although subjects experienced an increase in MRI-diagnosed pathological features with increasing LBP occurrence, no link could be established to provide causal factors to the development of new pain or pathology. This supports the idea that pathological change and the occurrence of non-specific low back pain in occupational workers is likely to co-incidental. * OR = Odds ratio CI = 95% Confidence interval viii

10 1 INTRODUCTION 1.1 BACKGROUND TO THE STUDY It is widely accepted that non-specific low back pain amongst the general population is highly prevalent. Approximately 80-90% of the population will experience low back pain at some point in their lives (Andersson, 1997) with most individual s experiencing pain at intermittent periods. Similar high prevalence rates are also evident in the work-place. Many individuals leave work due to repeated episodes of low back pain and consequently, reliable established risk factors for pain have been sought after. Many possible causative factors have been proposed, mostly focusing on various occupational, lifestyle and psychological characteristics but it is pathology of the lumbar spine that has continued to be studied to great extent. Although the scientific and clinical literature has housed much debate about the role pathology plays in low back pain, few firm conclusions have been drawn, particularly about the involvement of pathology in the development and progression of pain. Lumbar spinal pathology has been extensively studied to try to establish links with low back pain. Imaging techniques has been central to these studies, especially with the introduction of MRI. The use of MRI to investigate low back pain has expanded rapidly but with the increasing number of studies published, controversy about the relationship of MRI-diagnosed pathology to pain has grown. This originated from a high profile study by Jensen et al., (1994) which found that many subjects who were symptomatic showed clear evidence of pathologies like disc degeneration, disc protrusion, endplate abnormalities and spinal stenosis. But just as many asymptomatic subjects were found to have MRI-diagnosed pathological features present in their lumbar spines as well. The conclusion from this study relied on the assumption that if asymptomatic subjects have MRI-diagnosed abnormalities then their role in subjects with low back pain is irrelevant. However specific types of pain, such as sciatic pain, have been established as resulting from certain pathological abnormalities, such as disc extrusion and severe nerve root compression (Boos et al., 1995, Beattie et al., 2000). More recent studies have established links between disc degeneration and low back pain (Boos et al., 2000) and small follow-up studies have also observed positive trends between pathology and pain (Borenstein et al., 2001). Perhaps the role of pathologies, and in particular the interaction of pathologies and the process of pathological development or change in pain is more complex. Many epidemiological studies have concluded that social factors, psychological factors and genetics have recently been established as strong risk factors for non-specific low back pain (Polatin et al,. 1993, Sambrook et al., 1999, Videman et al., 2003, Carroll et al., 2004). These associations have also been found in the work-place. There is evidence to support the notion that certain characteristics of jobs are linked to pain reporting and symptoms (Andersson, 1999) but this does not necessarily provide a causative conclusion (Waddell & Burton, 2001). Occupational characteristics have been established as having a detrimental effect on spinal structures but again whether this leads to pain is yet to be determined. Longitudinal studies have presented evidence that heavy physical workloads may increase the risk of LBP (Macfarlane et al., 1997, Hartvigsen, et al., 2001) and other studies have associated lumbar movements with changes in the lumbar spine (Fujiwara et al., 2001). These studies suggest that both loads and postural influences, albeit small may have a cumulative and detrimental affect on the spine which may in turn lead to pain. There are few published studies that have investigated the longitudinal relationship between MRI-diagnosed pathology and low back pain. This is mainly due to cost issues and problems associated with retaining subjects or patients into a long study. Some have investigated present 1

11 MRI with past pain histories, with the argument that pathology accumulates over time and can therefore be related to past pain (Videman et al., 2003). But some pathological features are known to regress, for example disc protrusions which creates uncertainty as to when onset of pathology had occurred. The longitudinal studies that have been attempted and carried out are small in subject numbers and short in duration. Not enough pathological change has occurred to warrant a causative effect on low back pain. The biological process of spinal pathological development is slow to progress and the sequence of progression remains unclear. The effects of life-time factors like occupational characteristics and sporting activity on the development of pain has not been considered longitudinally either. Due to the intermittent nature of low back pain, subjects have a tendency to forget previous pain episodes that have happened across their life time. To this end, it is still unclear the role MRI-diagnosed pathological features and occupational factors may play in the presence, onset and worsening of low back pain. This study stems from a study by Savage et al., (1997) which addressed the issue of whether MRI could be used as a technique to establish future low back pain risk. 149 subjects from five different occupational groups were enrolled in the study and were asymptomatic on entry but were found to have experienced low back pain in the past to varying degrees. Spinal pathology was assessed from MRI scans and disc degeneration was found to be associated with increasing age. Although low back pain was found to be more common in the older subjects, there was no relationship between low back pain and disc degeneration. Occupation did not appear to be a factor in differentiating LBP sufferers either. After a one year follow-up, 13 subjects experienced low back pain for the first time, although there was no development of further pathological features or changes in the MRI appearance of the spine that could account for the newly developed pain. For this present study, these subjects have been re-recruited and subsequently followed up 10 years after their entry into the initial study, to firmly establish the longitudinal changes in MRI of the spine and whether these are related to pain occurrence. Although not designed from the outset as a longitudinal study, this study aims to firmly address the controversial issue of the long-term relationship between lifestyle factors in particular occupation, spinal pathology and low back pain. 1.2 AIMS AND OBJECTIVES The aims of the longitudinal study are two-fold; firstly to investigate pain as an outcome in relation to pathology and lifestyle factors and secondly to investigate the pathological process over the time period. The longitudinal study will address such questions with regard to subjects who developed low back pain since the original study what has happened to them? Is the presence of past MRIdiagnosed pathological features predictive of the onset of pain? Does the development or worsening of pathological features over time predict new onset low back pain in these subjects? For those subjects who were experiencing pain in the original study, is their worsening of pain determined by the development of new pathological features or worsening of previous ones? Subjects occupations, sporting activities and general well-being may be influencing their pain experience - Are lifestyle factors additional contributing factors to pain and if so, in which way (positive or negative)? 2

12 Due to the longitudinal nature of this study, changes in pathological features are expected to occur which will enable the process of pathological change over time to be investigated. Can risk factors for pathological change over time be determined to shed light on the sequence of pathological progression over time? And how do lifestyle factors impact on spinal pathology over the time period, when controlling for pain? There have been no longitudinal studies of this time span previously and it is expected that this study will be a valuable contribution to the understanding of the development and worsening of low back pain and spinal pathology. 3

13 2 METHODS 2.1 TRACING ORIGINAL SUBJECTS Ethics committee approval was granted for the follow-up study. Prior to this, a pilot study to determine whether all original 149 subjects could be traced was carried out. The original subjects contact details had been maintained in a database and various resources were utilised to verify names and addresses (e.g. Local Health Authority and Electoral register searches). Those subjects who were traced were sent a detailed low back pain questionnaire (see below) and were asked to consent to the use of their low back pain history and to a follow-up MRI scan of their lumbar spine. The table below shows the results of attempts to trace all 149 of the original subjects in the pilot study. 104 subjects LBP questionnaires were returned and of those, 96 agreed in 2001 to be scanned. The 104 responding subjects had an age range of 35 to 71 years old. The mean age was 52 years. Table 1 Results of the pilot study to follow-up the 149 original subjects Descriptive result of follow-up Subject numbers Consent to LBP questionnaire and MRI 96 Consent to LBP questionnaire only 8 Could not be traced by any method 25 Died 4 Unresponsive to questionnaire 13 No consent to LBP questionnaire or MRI 3 Overall Total LOW BACK PAIN QUESTIONNAIRE The low back pain questionnaire was a self-answered 60 question document with information pertaining to age, occupational history, characteristics of present and previous occupation ( Does your job involve lifting and carrying heavy items? and Does your job involve working in a stooped, twisted or awkward position? ) and history and frequency of sporting activities. LBP history, frequency, intensity (VAS scores), duration, location and words to describe pain was also obtained via various questions. LBP was identified as pain in the lower lumbar area. Questions pertaining to disability and psychological well being were also asked in the form of a disability index section (11 questions) and The General Health Questionnaire-12 (GHQ-12). 2.3 MRI SCANNING PROTOCOL Follow-up scan appointments were organised with subjects repeatedly contacted to encourage maximum attendance. During the scanning period 23 subjects withdrew from the study for various reasons. Of these 13 withdrew due to lack of interest, 2 due to ill health, 2 subjects did not turn up to appointments and 6 subjects did not respond to calls and letters to book appointments. In total 73 subjects returned to MARIARC to be scanned. Of these, 3 subjects could not be scanned successfully due to movement in the scanner (2 subjects) or because they could not physically fit (1 subject). 70 subjects were successfully scanned. The MRI scans of the lumbar spine were performed using a GE 1.5T Signa scanner system. Two consecutive protocols per subject were performed; a Coil protocol where a surface rectangular coil (5 x11 ) was used over the lumbar spine area and a Phased-array sequence 4

14 where a modern phased-array spine coil was used. The Coil protocol was performed to match that of the original study and was identical to the protocol in the 1988 study. The Phased-array protocol was performed to provide a more up-to-date protocol in line with current clinical lumbar spine scans, for comparison. The coils were placed in the lumbar region to acquire images of the lumbar spine from the L1 vertebral body level through to L5/S1 disc level inclusively The Coil protocol From coronal and sagittal localisers, 4 further series were prescribed (all with respiratory gating). 1. Sagittal dual echo sequence (TE:30ms and 90ms; TR:1500ms) with a 5mm slice thickness and a 1.5mm gap to provide proton density and T2-weighted images using a 256x128 matrix and a 24cm Field Of View (FOV) 2. Sagittal T1-weighted images (TE:20ms; TR:400ms) with a 5mm slice thickness and 1.5mm gap using a 256x128 matrix and 24cm FOV. From a midline sagittal image, axial slices were prescribed obliquely through the centre of each intervertebral disc from L1/L2 L5/S1 parallel to the endplate above. 3. Axial T1 images (TE:20ms; TR:400ms) with a 5mm slice thickness using a 256x256 matrix and 24cm FOV. 4. Axial T2 images (TE:90ms, TR:1500ms) with a 5mm slice thickness using 256x256 matrix and 24cm FOV The Phased-array protocol From coronal and sagittal localisers, 4 series were prescribed (all with respiratory gating). 1. Sagittal dual fast spin echo sequence (2 echoes TE:17ms and 102ms; TR:4500ms) with a 5mm slice thickness and a 1.5mm gap to provide proton density and T2-weighted images using a 256x256 matrix and a 24cm FOV. 2. Sagittal T1-weighted images (TE: minimum; TR:500ms) with a 5mm slice thickness and 1.5mm gap using a 256x256 matrix and 24cm FOV. From a midline sagittal image, axial slices were prescribed obliquely through the centre of each intervertebral disc from L1/L2 L5/S1 parallel to the endplate above. 3. Axial T1 images (TE: minimum; TR:500ms) with a 5mm slice thickness using a 256x256 matrix and 24cm FOV. 4. Axial T2 images (TE:102ms, TR:4000ms) with a 5mm slice thickness using 256x256 matrix and 24cm FOV. 2.4 PATHOLOGY CLASSIFICATION AND ASSESSMENT A Consultant Radiologist and Research Scientist reviewed the most recent scans and some of the older 1988 scans for pathological features. The most recent scans were filmed and then blinded to remove all the subjects information. The two reviewers, if disagreement about pathology classification occurred, debated the pathology and came to a final agreement. The classification systems to assess pathology encompassed the original assessment of pathology from the 1988 study but also satisfied the most recent acceptable criteria. The scientific literature provided an updated classification system for assessing disc degeneration (Pfirrmann et al., 2001). The existing classification system for herniation (Jensen et al., 1990) was modified and the classification systems for nerve root compression (NRC) and facet hypertrophy (FH) from the original study were used because more reliable classification systems could be found in the literature. 5

15 2.4.1 Disc Degeneration L1/L2 disc level Spinal canal L5/S1 disc level Figure 1 An example of disc degeneration on a mid-line sagittal T2-weighted image In Figure 1, L4/L5 is classified as a Grade 4 degenerated disc (no clear distinction between annulus and nucleus) and L5/S1 as a Grade V severely degenerated disc (collapsed disc space). From L1/L2 to L3/L4, the discs are classified as normal due to the brightness of the signal intensity (SI), which is comparable to the SI of the spinal canal. Disc degeneration was assessed individually at each disc level (L1/L2 L5/S1) using the algorithm described by Pfirrmann et al., (2001) which was based on the reduction in signal intensity on T2-weighted images as assessment. The system was a 5 point scale (Grade I=normal to Grade V=severely degenerated) Disc Herniation Disc herniation was assessed individually at each disc level (L1/L2 L5/S1) using the classification system described by Jensen et al., 1994 which was similar to the system used in the original study. An additional criterion of slight bulging was added to this classification system to differentiate different types of bulges noted on the scans. L1/L2 disc level Spinal canal L5/S1 disc level Figure 2 An example of disc herniation on a mid-line sagittal proton density image In Figure 2, L4/L5 is classified as a protruded disc due to the stretching of the posterior longitudinal ligament and the appearance of an annular tear. L1/L2 and L3/L4 discs have no bulges or protrusions and are classified as normal. Although the scientific literature discusses in detail various classification systems for herniation (for example Milette, 2000) agreement on a suitable classification system for use in this study remained with that described by Jensen et al.,

16 2.4.3 Nerve root compression Nerve root compression was assessed individually at each disc level (L1/L2 L5/S1) on sagittal images and axial images. NRC was assessed independently of herniation and a 3 point classification system was used; 0=normal (no compression), 1=no clear fat interface around the nerve root on either sagittal or axial images, or 2=compression of nerve root with or without deviation on both sagittal and axial images. Figure 3 An example of nerve root compression on a T1-weighted axial Figure 3 shows the right L4/L5 nerve root as classified as compressed due to the absence of a clear fat interface around the nerve root (as seen in the magnified section above) Facet hypertrophy Facet hypertrophy was assessed individually at each disc level (L1/L2 L5/S1) for hypertrophic changes on axial images. Pairs of facet joints were assessed at each spinal level and classified together. A 3 point classification system was used: 0=normal (no facet hypertrophy), 1=mild (slight indication of hypertrophy/ossification of joints, or 2=marked (clear ossification and hypertrophy of joints). Figure 4 An example of facet hypertrophy on a T1-weighted axial image 7

17 In Figure 4, the L4/L5 facet joint is classified as hypertrophied as clear ossification of the joints can been seen (see magnified section above) which protrude out into the surrounding space. Other features on the scans noted by the reviewers were also recorded, for example the presence of annular tears, Modic changes in the endplates and Schmorl s nodes. As previously mentioned, the classification systems from the original 1988 study and most recently study were different. The original 1988 study data were converted into the most recent classification systems to create consistency across the longitudinal data. Conversion of these systems is represented in Figure 5. Degeneration Herniation NRC FH 0=normal 4=degenerate 1=normal 3=protrusion 2=bulging 4=extrusion 1=normal 2=mild 3=marked 1=normal 2=mild 3=marked 1=normal 2=slight 3=mild 4=moderate 5=severe 1=normal 2=slight 3=bulging 4=protrusion 5=extrusion 1=normal 2=mild 3=marked 1=normal 2=mild 3=marked 0=normal 1=degenerate 0=normal 1=herniated 0=normal 1=NRC 0=normal 1=FH Figure 5 Schematic diagram to represent the conversion of the 1988 pathology classification system into the most recent pathology classification system and then into dichotomous variables The coloured bars represent the different classification systems from 1988 (top; light blue bar) through to 2002 (middle; dark blue bar) and dichotomous (bottom; red bar) classification systems. Four characteristics of spinal pathology were assessed from the MRI scans. NRC Nerve root compression, FH Facet hypertrophy BASELINE STUDY DATA The low back pain history and MRI data from the 1988 study were used as baseline data for this study. All subjects entered the 1988 study as asymptomatic however it was established that subjects had experienced pain in the past when questioned. Four low back pain (LBP) status groups were established for the subjects. These were No LBP (never experienced LBP), Past LBP (subjects who had experienced LBP in the past but not in the 12 months preceding the MRI scan), LBP 12 (subjects who had experienced LBP in the 12 months preceding the MRI scan, but not every month) and LBP monthly (subjects who had experienced LBP at least once a month in the 12 months preceding the MRI scan). All 149 subjects LBP status group membership were identified. 8

18 40 subjects old 1988 MRI data were located and reviewed for pathological features with the up-to-date classification systems. Due to the lack of original scans, the 1988 MRI reports were located and used as baseline data. To ensure this data was accurate and could be compared with newly reviewed 1988 MRI data, a statistical comparison was made and a kappa agreement statistic of 0.78 was found for overall pathology reporting. This is statistically significant at the 5% level and represents a substantial agreement (Landis & Koch, 1977) STUDY DATA Detailed personal and low back pain history information had been provided by the 104 responders to the follow-up via the follow-up questionnaire. The personal and occupational information was checked for consistencies with the 1988 questionnaire (where possible). Subjects were assigned to LBP groups as defined in the 1988 study. The two status groups from 1988 and 2002 were then compared to determine change over time, onset of new LBP (i.e. onset of any LBP frequency from no previous LBP at all) and worsening of LBP (i.e. an increase in frequency of LBP over the study time period). The latter two descriptions of low back pain were assembled into dichotomous variables for statistical analysis. Onset of LBP was defined as all those subjects who were members of the 1988 No LBP ever group and who then were assigned to any one of the pain groups in Worsening of LBP was defined as all those subjects who had been members of any one of the pain groups in 1988 and who then were assigned to a more severe pain group in For those subjects who group status could not worsen (i.e. those already experiencing pain on a monthly basis in 1988) an additional answer from the 2002 questionnaire relating to frequency was used to assess their worsening of pain status. 2.7 STATISTICAL ANALYSIS Continuous variables are expressed as mean ± SD and categorical variables are expressed as proportions. Comparisons between continuous variables were made with t-tests or chi-squared tests. Categorical data were analysed using various non-parametric tests depending on whether the data was nominal or ordinal in nature. In order to determine statistically the possible long-term relationship between MRI findings and LBP, logistic regression analysis was chosen as the most appropriate way to determine potential risk factors for future pain. Univariate analyses of potential predictors for LBP were performed by calculating odds ratios (OR) with 95% confidence intervals. Variables with a p-value of up to and including 0.1 were then consecutively subjected to a multivariate logistic regression model to assess the independent impact of each risk factor on LBP. A forced entry procedure was used with a p- value of less than 0.05 to eliminate variables. All statistics were performed using SPSS statistical package 11.0 (SPSS Inc., Chicago, IL). 9

19 3 RESULTS 3.1 ANALYSIS OF RESPONDERS Potential bias may have been introduced to the follow-up study due to the type of subjects who responded to the follow-up. Particular reasons may have influenced their decision to respond, for example, worsening LBP or being told of pathology in the spine during the interim period between the two studies. Statistical analysis was performed to identify whether responders baseline data had different to those that did not respond (non-responders) to the follow-up. The following table (Table 2) presents the number of subjects who responded to the follow-up study subdivided into the original occupational groups and age groups. Responders differed significantly from non-responders with regard to occupational groups (Kruskal-Wallis p=0.036). A high percentage of office workers and ambulance men responded to the follow-up study. Overall significantly fewer manual workers responded to the follow-up study (Kruskal-Wallis p=0.02 for manual workers combined vs. office workers). Table 2 Numbers of subjects (percentage) who responded to the follow-up study Occupational groups (1988) Subject responding to 2002 Follow-up Younger age group Older age group Total Office workers 25 (76%) 21 (88% 46 (81%) Ambulance men 12 (71%) 7 (100%) 19 (79%) Dray n/a 8 (67%) 8 (67%) Car assembly workers 7 (39%) 14 (64%) 21 (53%) Porters 3 (43%) 7 (78%) 10 (63%) Total 37 (49%) 57 (77%) 104 (70%) There was no difference found between responders and non-responders with regard to age groups (Kruskal-Wallis p=0.057). But a difference was found between the mean age of responders and those that didn t, with responders having a slightly older mean age (responders - 52yrs, nonresponders - 48yrs; 2-tailed t-test p=0.048). No significant differences (Mann-Whitney U tests, 2-tailed p>0.05) were found between responders and non-responders, with regard to MRI-diagnosed pathological data (all criteria) from In addition there were no significant differences (Mann-Whitney U tests, 2-tailed p<0.05) between scanned responders (which totalled 70) and those that did not return for a scan with regard to MRI-diagnosed pathological data from the 1988 study. No significant differences (Mann-Whitney U tests, 2-tailed p>0.05) were found between responders and non- responders with regard to 1988 LBP status (all groups). 3.2 RESPONDERS ORIGINAL 1988 BASELINE DATA In order for the follow-up data to be comparable, an analysis of the responders original 1988 data was conducted. 10

20 3.2.1 Demographic and low back pain data Table 3 presents the 1988 demographic data for the follow-up subjects and includes total number of subjects per occupation, 1988 mean age ± SD, and 1988 LBP status. The majority of follow-up subjects were office staff (as in the original study) and only a small number of dray men participated. The majority of office staff reported never having LBP in 1988 and reported having the least frequent LBP out of all the occupations. Table 3 Demographic 1988 baseline data for all the 104 returning subjects. Mutually exclusive back groups (MEBG) indicate LBP status at the time of the original study 1988 Age in Low Back Pain status 1988 data (MEBG) Occupation N (%) years (mean ±SD) No LBP Past LBP LBP-12 Office workers (Sedentary) LBPmonthly 46 (44.2%) 37.4± (43.5%) 8 (17.4%) 7 (15.2%) 11 (23.9%) *Ambulance 19 (18.3%) 30.3±8.9 6 (31.6%) 2 (10.5%) 6 (31.6%) 5 (26.3%) *Dray 8 (7.7%) 48.9±5.8 1 (12.5%) 0 2 (25%) 5 (62.5%) *Car production 21 (20.2%) 39.1± (28.6%) 3 (14.3%) 6 (28.6%) 6 (28.6%) *Porter 10 (9.6%) 39.8± (30%) 1 (10%) 3 (30%) 3 (30%) * = Manual combined 58 (55.8%) 37.7± (27.6%) 6 (10.3%) 17 (29.3%) 19 (32.8%) Total 104 (100%) 37.6± (34.6%) 14 (13.5%) 24 (23.1%) 30 (28.8%) A significant difference was found between the (1-way ANOVA, p=0.006) between the mean ages of the occupational groups with post-hoc tests indicating a difference between the dray and ambulance men (Bonferroni, p=0.003). No relationship between LBP status and the occupational groups from the 1988 data could be established (Kruskal-Wallis, p=0.16). A relationship between age and LBP status was established for these data (1-way ANOVA, p=0.02) with post-hoc tests (Bonferroni, p=0.02) indicating that subjects reporting LBP-monthly were significantly older (mean age ±SD: 42±11.6) than those reporting No LBP (mean age ±SD: 33±11.9) MRI pathological data Table 4 shows the number of discs affected by pathology as reported from the MRI scans from 1988 for the 104 subjects returning to the study. Dichotomous values are used for simplicity. The majority of discs affected by pathology were at the L4/L5 and the L5/S1 disc levels. The number of discs with pathology increases down the spinal levels. Degeneration occurred more frequently in the discs than any other pathology whilst disc herniation and nerve root compression were the least frequent features. Facet hypertrophy occurred mostly at the L4/L5 disc level. 11

21 Table 4 Number (percentage) of MRI-diagnosed pathologically affected discs at each disc level of the spine Disc level 1988 Dichotomous MRI Number of discs affected Degeneration Herniation NRC FH L1/L2 6 (5.8%) 0 (0%) 0 (%) 1 (1 %) L2/L3 6 (5.8%) 1 (1%) 1 (1 %) 3 (2.9%) L3/L4 6 (5.8%) 0 (0%) 1 (1.4%) 3 (2.9%) L4/L5 21 (20.2%) 4 (3.8%) 3 (2.9%) 4 (3.8%) L5/S1 34 (32.7%) 5 (4.8%) 3 (2.9%) 2 (1.9%) Total 73 (14%) 10 (1.9%) 6 (1.5%) 13 (2.5%) NRC nerve root compression FH facet hypertrophy The majority of subjects had just one pathological feature present at an affected disc level. Only 1 subject presented with all 4 pathological features, which was at the L2/L3 level. 4 subjects had a combination of degeneration and herniation at L4/L5 out of 8 subjects who had multiple pathologies at that level. 4 subjects also had a combination of degeneration and herniation at L5/S1 disc level which were the most common combined pathologies at that disc level. In addition, having pathological features at one or more levels occurred most frequently for degenerated discs. Out of the 45 subjects with some degeneration in their lumbar spine, 17 (38%) subjects had this at more than 2 disc levels. 1 subject had degenerated discs at all disc levels. Only 1 subject had a herniated disc at 2 disc levels, which were L4/L5 and L5/S1. Just over half (52%) were found to have a normal spine, indicating that no MRI-diagnosed pathological features could be found at any lumbar spinal level. 48% had at least 1 pathological feature present in their lumbar spine Relationship between previous pathology, age, occupation and low back pain Having at least 1 disc level affected by disc degeneration in the spine was significantly related to age (Fisher s exact test, p=0.032) with the older age group (>30yrs old) 3 times (OR 3.0 CI: ) more likely to have a degenerated disc than the younger age group ( 30yrs old). No relationship was found between disc degeneration and occupation (Fisher s exact test, p=0.24) and no relationship between disc degeneration and LBP status (chi-squared test, p=0.43) was found either. No significant difference was found between subjects in the younger ( 30 yrs) and older (> 30 yrs) age groups with regard to having at least 1 herniated disc in the spine (Fisher s exact test, p=0.18). No statistically significant relationship was found between disc herniation and occupation (chisquared test, p=0.23). There was no statistical relationship between disc herniation and LBP status (chi-squared test, p=0.26). All subjects with at least 1 compressed nerve root in their spine were in the older age group (>30 yrs) which resulted in a significant difference between the age groups (Fisher s exact test, p=0.03). A statistically significant relationship was found between nerve root compression and occupation (chi-squared test, p=0.002) with a quarter of draymen presenting with compression. There was no statistical relationship between nerve root compression and LBP status (chi-squared test, p=0.58). No relationship could be found between the younger and older age groups with regard to facet joint hypertrophy (Fisher s exact test, p=0.11). Neither occupational group status nor LBP status were related to the presence of facet joint hypertrophy (occupational status - chi-squared test, p=0.87; LBP status - chi-squared test, p=0.25). 12

22 Overall, having an abnormal lumbar spine was not related to LBP status in 1988 as presented in Figure 6. A chi-squared test to examine whether a relationship existed between 1988 LBP status and MRI-diagnosed spinal pathological status was non-significant (p=0.5). 40 Abnormal spine Normal spine 30 Number of subjects No LBP ever Past LBP >12 Past LBP < 12 LBP monthly in months ago months ago past 12 LBP status 1988 Figure 6 Bar chart representing the number of follow-up subjects with normal and abnormal spines diagnosed from the 1988 MRI lumbar spine scans in terms of 1988 LBP status groups No clear relationship between 1988 LBP status and having an abnormal or normal spine could be found. Over a third (36%) of the subjects with no LBP had at least one form of pathology in their spine and 40% of subjects experiencing pain on a monthly basis had normal spines. Although not statistically significant, it was apparent that as the frequency of pain increased, so did the proportion of abnormal spines. 3.3 ANALYSIS OF CONTRIBUTING FACTORS TO LOW BACK PAIN An analysis of all the possible factors that may contribute to the outcome of frequent pain was performed. For the 104 follow-up subjects, logistic regression analysis was performed for their 13

23 1988 data to examine whether a relationship existed between age, occupation, 1988 MRI-diagnosed pathology and 1988 frequent LBP reporting (LBP monthly). All potential factors were assessed on a univariate basis and if found to be significant (p-value 0.1), were entered into multiple regression analysis to assess independence from the other potential factors. Table 5 presents the results of these analyses. Table 5 Univariate and multivariate logistic regression results for predicting the outcome of frequent LBP Variable Univariate OR and CI p-value Multivariate OR and CI p-value Age 1.04 CI: p=0.04* 1.03 CI: p=0.13 Degeneration 1.47 CI: p=0.38 Herniation 3.50 CI: p=0.08* 2.5 CI: p=0.2 NRC 5.21 CI: p=0.2 FH 2.69 CI: p=0.2 Occupation Office 1 1 Ambulance 1.1 CI: p=0.8 Dray 5.3 CI: p=0.04* 3.4 CI: p=0.2 Car production 1.3 CI: p=0.7 Porter 1.4 CI: p=0.7 Odds ratios (OR) and confidence intervals (CI) are presented for each factor. Occupation is referred to against office workers. *represents significant p-values. NRC nerve root compression, FH facet hypertrophy Age, having at least 1 herniated disc and working as a drayman were found to be associated with frequent reporting of LBP in 1988 however the multivariate analysis produced no single significant variables. This indicates that none of the above variables significantly contributed to the frequent reporting of LBP in these subjects in As reported in the original study of 149 subjects (Savage et al., 1997) no clear relationship between age, pathology, occupation and LBP could be concluded. 14

24 3.4 FOLLOW-UP DATA Demographic and low back pain data The follow-up subjects demographic data is shown in Table 6. Longest occupation, age started and length of service in the longest occupation were determined from the 1988 and 2002 questionnaires. Subject s follow-up LBP status is also presented. Table 6 Demographic and LBP status follow-up data for all 104 subjects returning to the study Longest Occupation Office workers (Sedentary) *Ambulance *Dray *Car production *Porter Other job * =Manual combined Total N (%) 43 (41.3%) 17 (16.3%) 8 (7.7%) 19 (18.3%) 10 (9.6%) 7 (6.7%) 54 (55.8%) 104 (100%) Mean no. of years ± SD in longest occup. Mean age ± SD started longest occup. Age in years now (mean ±SD) 23.1± ± ± ± ± ± ± ± ± ± ± ±11.8 LBP status 2002 No LBP 10 (23.3%) 2 (11.8%) 1 (12.5%) 2 (10.5%) Past LBP 12 (27.9%) 2 (11.8%) 1 (12.5%) 3 (15.8%) LBP (23.3%) 2 (11.8%) LBPmonthly 11 (25.6%) 11 (64.7%) 0 6 (75%) 3 (15.8%) 11 (57.9%) 19.5± ± ± (30%) 7 (70%) 15.6± ± ± ± ± ± ± ± ± (14.3%) 5 (9.3%) 16 (15.4%) 2 (28.6%) 6 (11.1%) 20 (19.2%) 3 (42.9%) 8 (14.8%) 21 (20.2%) 1 (14.3%) 35 (64.8%) 47 (45.2%) 93% of the subjects longest occupation was their 1988 job. A significant difference was found between the occupational groups, with regard to the mean number of years subjects had worked in their longest job (1-way ANOVA, p=0.001). Dray men spent significantly more years working continuously in their job compared to any of the other manual occupations or other jobs (Bonferroni post-hoc tests: dray vs. ambulance p=0.005, vs. car production p=0.004, vs. porter p=0.016 and vs. other job p=0.002). A significant difference was found between occupational groups with regard to the age subjects started their longest occupations (1-way ANOVA, p=0.0001). Post-hoc tests confirmed that office workers and ambulance men were each significantly of a younger starting age compared to the car production workers and porters (Bonferroni tests: office vs. car production p=0.019, office vs. porters p=0.034, ambulance vs. car production p=0.001, ambulance vs. porters p=0.002). 15

25 However when the combined manual occupations were compared to the other job category and office workers, there were no significant differences found between the groups for either number of years in longest occupation (1-way ANOVA, p=0.1) or for age started longest occupation (1-way ANOVA, p=0.25). Nearly half of the subjects reported that their LBP occurred on a monthly basis. A significant relationship existed between subjects longest occupations and present LBP status (Kruskal-Wallis, p=0.004), with more dray men and porters reporting LBP on a monthly basis than other occupations. Similarly, when the longest manual occupations were combined and compared to the office workers, a significant relationship remained (Kruskal-Wallis, p=0.0004) between longest occupation and present LBP status. 65% of subjects whose longest occupation was a manual one reported LBP on a monthly basis. There was no relationship established between age and LBP status (1-way ANOVA, p=0.44) which was in contrast to the data from Descriptive follow-up subject information Additional detail about subjects occupations, sport, LBP characteristics and general well-being were obtained from the follow-up questionnaire. Descriptive data are displayed as proportions and confidence intervals in Table 7. Occupational characteristics and sport With regard to occupation, 58% of subjects were working, either full-time or part-time. Of the 58% working, 97% of them were still working in their 1988 jobs. Of the 42% not working, three quarters had retired from their jobs, whilst the remaining quarter had stopped working due to ill-health. 48% of subjects said they regularly lifted heavy objects during their longest occupation. All (100%) draymen, 90% of porters and only 12% office staff reported this. 57% of subjects reported working in a stooped, twisted or awkward position on a regular basis in their longest occupation. 100% of dray men, 89.5% of car production workers and only 12% of office staff reported this. 7% of subjects reported taking time off-sick from work for at least a week or longer due to LBP. These subjects significantly reported higher pain frequency than subjects who took less time off work (Kendall s tau, p=0.01). 7 subjects had to change their job due to LBP since the 1988 study with 5 of those subjects changing their job in the past 12 months. All 7 subjects significantly expressed having frequent pain on a regular basis compared to subjects who hadn t changed jobs (Kendall s tau, p=0.01). 54% of subjects reported doing sport at least once a week or more and 10% said they did some form of sport everyday. 14% said they never did any sport at all. Neither occupation nor age were related to the frequency of sport done (occupation chi-squared test, p=0.49; age Fisher s exact test, p=0.3). No relationship could be established between frequency of sporting activities and LBP status (Kendall s tau, p=0.35). Characteristics of LBP and well-being 38% of all subjects reported pain spreading to their legs frequently. 32% of subjects said they had been to see their GP or another professional about their pain in the last year. The majority of those subjects (81%) had LBP on a monthly basis. Most subjects reported that their worst pain ever experienced lasted for about a day (38%). 33% reported pain lasting a week. The mean (±SD) VAS score (scale of 0-10) for the worst pain 16