Lumbar multifidus muscle morphology is associated with low back-related pain duration, disability, and leg pain: a cross-sectional study in secondary care.

DOI: https://doi.org/10.21203/rs.3.rs-1724016/v1

Abstract

Background: Systematic reviews and studies exploring associations between morphologic change of paraspinal muscles and low back pain or related outcomes such as disability, radiculopathy, and physical workload, have reported conflicting results. This study explores the associations between lumbar multifidus muscle quality and clinical outcomes related to low back pain.

Methods: Cross-sectional study of spinal clinic outpatients presenting with a primary complaint of low back and/or leg symptoms. Univariable and multivariable regression models were used to investigate associations between MRI-based multifidus muscle cross-sectional area at L4 and L5 and clinical outcomes for low back and leg pain, disability, restricted motion, and strenuous nature of work. Results were reported with β-coefficients, odds ratios (OR), or incidence rate ratios (IRR) and their corresponding 95% confidence intervals, based on a 10% difference in muscle quality for each clinical variable. Multivariable analyses were adjusted for age, sex, and BMI.

Results: 875 patients [487 females; mean (SD) age: 43.6 (10.2) years] were included. In the multivariable analyses, muscle quality was significantly associated with disability (0-23 scale) [β: -0.74, 95% CI: -1.14, -0.34], leg pain intensity (0-10 scale) [β: -0.25, 95% CI: -0.46, -0.03], and current pain duration of more than 12 months [OR: 1.27, 95% CI: 1.03, 1.55]. No associations were found for low back pain intensity, morning stiffness, painful active range of motion, or work nature.

Conclusions: Patients with higher lumbar multifidus muscle quality reported lower levels of low back pain-related disability and leg pain intensity, indicating that muscle quality may play a role in the etiology of lumbar spine disorders. However, the clinical importance of these associations is uncertain. Future longitudinal studies are needed to understand the effect of lumbar multifidus muscle quality on lumbar-related pain and disability. 


Introduction

Despite intensive research efforts to enhance our understanding of the causes and management of low back pain (LBP), this disorder has become one of the ten most important drivers increasing the global disease burden. It remains ranked 1st among causes of years lived with disability (YLD), is responsible for 7.4% of total global YLD, is found in all age groups from 5 years and older, and in 2019 had a reported overall prevalence rate/100,000 population of 6972.5 [1].

As LBP due to a specific pathology is rare (< 10%), most patients are classified as experiencing either non-specific LBP (~ 90–95%) or, less frequently, LBP with an associated radicular syndrome (~ 5–10%) [2, 3]. In their 2001 review of LBP, Deyo and Weinstein discussed all the factors currently considered to play a key role in the aetiology and management of LBP [4]. At that time, paraspinal muscle morphology was not mentioned as a risk factor for specific or non-specific back pain. Since then, there has been a growing focus on spinal function, specifically looking at the intrinsic paraspinal musculature and the role of the lumbar multifidi muscles (LMM) in the cause, progression, and outcomes of LBP [5].

The LMM are complex structures that provide a unique contribution to lumbar spine stability [6, 7], accounting for approximately 2/3rd of the stability at the L4/L5 segment [8]. Spinal instability is a theorized mechanism of LBP used to justify therapies from exercise to surgical fusion [911], and while a systematic review by Fortin et al. [12] reported that the preponderance of evidence supports an association between low back pain and morphologic change of paraspinal muscles (i.e., changes in the quantity or quality of muscle tissue, including fatty infiltration), several subsequent papers on this topic have reported conflicting findings [1317]. Additional studies investigating specific clinical or activity-related features related to LBP, including pain duration, disability, or pain intensity [1822], physical function and muscle stiffness [16, 23, 24], physical demands of work [25], and radiculopathy-related outcomes [2629], have also shown conflicting outcomes, failed to account for relevant confounders, or only had access to small to moderate population samples.

Therefore, the objective of this study was to explore the cross-sectional associations of LMM quality with pain, disability, spinal function, and work history among patients with non-specific LBP and/or back-related leg pain. We hypothesized that greater LMM quality would be associated with better clinical outcomes.

Methods

For this study, all patients presenting to the Spine Centre of Southern Denmark from September 2013 to October 2014 with a primary complaint of LBP and/or radicular symptoms, who agreed to complete a comprehensive, prescribed electronic or paper-based clinical history questionnaire and undergo a standardized physical examination by a qualified clinician (i.e., a medical doctor, chiropractor, or physiotherapist), had their responses/results recorded in the SpineData registry [30]. From this pool, patients who also had recent lumbar MRIs available from the local hospital radiology department were eligible for inclusion. Patients with missing demographic information or with a significant cause of low back pain (e.g., malignancy, infection, recent fracture) were excluded.

The clinical data from the SpineData registry were originally collected as part of a cohort study approved by the Danish Data Protection Agency for the Region of Southern Denmark (Journal number: 2008-58-0035-15/22513), performed following the Declaration of Helsinki principles, with signed informed consent from all patients. Danish law does not require ethical approval from the Regional Committees on Health Research Ethics for Southern Denmark to access this data (a letter of exemption is available in Danish from the authors on request). Approval for the analysis of this data within a larger project was provided by our university’s Human Research Ethics Committee (approval: 2017/110). A full description of the development and scope of the SpineData registry has been previously published [30].

MRI acquisition and muscle measurement

Patient’s images were obtained using a body/spine coil on either a 1.0 T Philips Panorama (Best, The Netherlands) or 1.5 T Philips Achieva (Best, The Netherlands) MRI system. Axial T2-weighted turbo spin echo (TSE) sequences (angled along the L3/4 – L5/S1 disc planes) were used for muscle analysis, while sagittal T1-weighted TSE sequences were used to assist with slice level localization. On the T2-weighted TSE axial images, the LMM were measured at L4/5 and L5/S1 bilaterally below the level of the exiting nerve roots, using a slice running through the disc or along/near the lower endplate, depending on which image provided the fullest/clearest posterior arch anatomy and LMM outlines. During the image selection process, cases were excluded if they demonstrated at least one of the following: 1) failure to include the L4/5 or L5/S1 level; 2) any indication of surgery from L4 to S1; 3) no MRIs or T2-weighted axial images were provided; 4) duplicate cases; 5) poor image quality overall; 6) partial visualization or slice overlap artefact involving the LMM at either level; and 7) distorted or unidentifiable L4 or L5 posterior arch anatomy.

All LMM measures were performed with sliceOmatic v5.0.8b [TomoVision, Magog, Canada]. Measurements were undertaken by an investigator with over 30 years of experience in spinal MRI interpretation, previous experience using sliceOmatic software in LMM analysis, and excellent reliability in performing the below-described measurement method [31]. The investigator was blinded to the patients’ demographic and outcome data prior to and during the measurement period. Muscle assessment focused on quality (i.e., pure muscle component) rather than quantity (i.e., total muscle area), as this may help provide a more nuanced muscle analysis and overcome shortcomings identified previously. For example, measures of total cross-sectional area fail to account for natural variations in overall LMM size or to address proportionate changes between muscle and fat) [5, 21].

To provide a reproducible estimate of pure muscle tissue, the maximum muscle signal intensity peak (single or multiple) within the image histogram (Fig. 1A, B) was identified. This histogram represented the range of tissue signals across the image, with darker tissues (e.g., pure muscle) predominating at the lower end of the histogram scale. Next, the LMMs were outlined using the protocols developed for previous studies [5, 32], to determine the total cross-sectional area (Fig. 2A, B), and the percent of peak muscle cross-sectional area (% MCSA) determined. Finally, the average % MCSA for all muscles at L4 and L5, and the lowest % MCSA for any muscle at L4 or L5, were calculated. The full details of this LMM measurement protocol have been previously reported [31].

Demographic information and clinical outcomes

We collected demographic information comprising age, sex, and self-reported height (cm) and weight (kg) for Body Mass Index (BMI) calculation. Clinical outcomes relating to pain characteristics, LBP-related disability, occupational history, and physical examination findings were also included. The length of time since current low back or leg pain onset was categorized as: <3 months, 3–12 months, or > 12 months). We used separate,11-point (0–10) numeric pain scales (NPS) to quantify low back and leg pain intensity, calculated as the average of: the current pain rating and the typical and worst pain ratings over the preceding 14 days [33]. Patients rated their level of low back pain-related disability using the 23-item version (0–23 scale) Roland Morris Disability Questionnaire (RMDQ) [34]. Low back morning stiffness was reported as: none, < 30 minutes, 30–60 minutes, or > 60 minutes. Currently employed patients rated the physical demands of their work on a 10-point scale (1–10), with a higher rating indicating a more strenuous work environment.

Physical examination outcomes included active lumbar range of motion and signs of lumbar radiculopathy. The clinician recorded the number of directions in which the patient indicated painful lumbar movement (flexion/extension, right/left rotation, right/left lateral flexion), and if they noted right or left-sided leg pain with signs of nerve root involvement (NRI) (defined as one or more of the following: a true positive straight-leg raise (SLR) test, or impaired deep tendon reflex, reduced muscle strength, or altered dermatome sensation of the painful extremity) [35].

Statistical methods

Descriptive statistics for demographic, clinical, and physical examination variables were calculated. To investigate the associations between LMM morphology and the clinical measures, we constructed separate univariable regression models, for each LMM measure (average and lowest % MCSA), per outcome. Model types depended on the nature of the dependent variables and their distributions. Linear models were used for normally distributed continuous outcomes (average LBP rating; RMDQ score), Poisson models for count outcomes (total directions painful active range of motion (AROM)), Tobit models for censored outcomes with floor/ceiling effects (leg pain intensity), gamma models for negatively skewed outcomes (work rating), and multinomial logistic models for categorical outcomes (time since pain onset; morning stiffness; signs of NRI and leg pain). Residuals diagnostics were used to check model fit. Results were summarized according to model type with beta coefficients with standard errors, odds ratios (OR), or incidence rate ratios (IRR), and corresponding 95% confidence intervals. We also constructed adjusted models, accounting for age, sex, and BMI as potential confounders [36]. All regression outcomes are reported based on a 10% difference in muscle quality. All hypotheses were two-sided, and significance levels for all analyses were set at α = 0.05. All data were analyzed using Stata I/C version 17.0 (StataCorp, College Station, TX).

Results

The patient selection process is presented in Figure 3. After excluding those with missing demographic data or for image-related reasons noted previously, 875 patients were eligible for inclusion in the final analysis. In some instances, either the patient or examining clinician did not provide input for a specific clinical variable, which resulted in a reduction of the number of evaluated cases for those variables. Additionally, only patients indicating current, active employment were included in the work rating analysis. The final descriptive data are summarized in Table 1. The mean (SD) age was 43.6 (10.2); females comprised 55.7% of patients. Duration of current pain ranged from less than one month to over 40 years, with 2.3% of patients reporting no current LBP and 13.4% reporting no current leg pain. All patients identified some level of low back disability, and the majority (63%) of employed patients indicated a less strenuous work history.  


Table 1: Descriptive statistics for demographic, muscle, and clinical variables.

                                

Demographic variables

N


 

Age (years, at 1st visit)

875

43.6 (10.2)

 

BMI (kg/m2)

875

26.7 (4.8)

 

Female sex

875

487 (55.7%)

 

Muscle variables

 

 

 

Average % MCSA 

875

35.4 (11.9)

 

Lowest % MCSA 

875

28.9 (11.8)

 

Clinical variables

 

 

 

LBP intensity (0-10)

875

5.8 (2.2)

 

Leg pain intensity (0-10)

870

4.5 (2.9)

 

Low back pain-related disability (0-23)

864

13.1 (5.6)

 

Strenuous work history rating (1-10)

571

4.5 (2.8)

 

Symptom duration 

875

 

 

< 3 months

 

 

182 (21.0%)

 

3-12 months

 

 

323 (37.3%)

 

 > 12 months

 

 

360 (41.6%)

 

Low back morning stiffness 

871

 

None

 

 

204 (23.4%)

 

Present <30 minutes

 

 

216 (24.8%)

 

Present 30-60 minutes

 

 

209 (24.0%)

 

Present >60 minutes

 

 

242 (27.8%)

 

Painful lumbar AROM 

690

 

No painful AROM

 

 

62 (9.0%)

 

Pain: 1 direction

 

 

152 (22.0%)

 

Pain: 2 directions

 

 

208 (30.1%)

 

Pain: 3 directions

 

 

104 (15.1%)

 

Pain: 4 directions

 

 

71 (10.3%)

 

Pain: 5 directions

 

 

30 (4.4%)

 

Pain: all directions

 

 

63 (9.1%)

 

Leg pain and NRI signs 

769

 

No leg pain

 

 

117 (15.2%)

 

Leg pain with no signs of NRI

 

 

328 (42.7%)

 

Leg pain with signs of NRI

 

 

324 (42.1%)

 












Values are mean (SD) or counts (%). % MCSA = proportion of peak muscle cross-sectional area; LBP = low back pain; AROM = active range of motion; NRI = nerve root involvement. 


Model results are reported in Tables 2 and 3. Univariable models for the average % MCSA and lowest % MCSA demonstrated small but significant negative associations between lower muscle quality and greater leg pain intensity, low back disability, and likelihood of leg pain with signs of NRI. Conversely, higher muscle quality was associated with an increased risk of pain duration longer than 12 months. After adjusting for confounders, low back pain-related disability [β: -0.66, 95% CI: -1.05, -0.26] and pain onset duration over 12 months [OR: 1.28, 95% CI: 1.04, 1.55] retained their associations with LMM quality for average % MCSA. Similarly for the lowest % MCSA, low back pain-related disability [β: -0.74, 95% CI: -1.14, -0.34], leg pain intensity [β: -0.25, 95% CI: -0.46, -0.03], and pain onset duration over 12 months [OR: 1.27, 95% CI: 1.03, 1.55] also remained associated with LMM quality. There were no associations between LMM quality and LBP intensity, presence or length of morning stiffness, number of directions with painful lumbar AROM, or the physically strenuous nature of the patient’s work.


Table 2: Associations between average % MCSA and outcomes.

 

 

 

 

Univariable model

 

 

Adjusted model

Outcome

N

Est.

95%CI 

N

Est.

95%CI 

Symptom duration1 

<3 months

875

ref

ref

875

ref

ref

3 to 12 months

 

 

1.12

0.95, 1.29

 

 

1.10

0.90, 1.36

>12 months

 

 

1.26

1.08, 1.47

 

 

1.28

1.04, 1.55

LBP intensity

875

-0.03

-0.15, 0.09

875

-0.11

-0.27, 0.05

Leg pain intensity2

870

-0.27

-0.43, -0.11

870

-0.20

-0.41, 0.01

Low back disability

864

-0.63

-0.94, -0.32

864

-0.66

-1.05, -0.26

Morning stiffness1 

None

871

ref

ref

871

ref

ref

<30 minutes

 

 

1.07

0.91, 1.27

 

 

1.03

0.83, 1.28

30 to 60 minutes

 

 

1.05

0.89, 1.23

 

 

1.06

0.86, 1.32

>60 minutes

 

 

1.00

0.86, 1.17

 

 

0.97

0.79, 1.20 

Physically strenuous work rating3

571

0.00

-0.01, 0.01

571

0.01

0.00, 0.02

Directions with painful ROM (total)4

690

0.98

0.94, 1.02

690

0.99

0.94, 1.04

Leg pain and NRI signs1

No leg pain

769

ref

ref

769

ref

ref

Leg pain, no NRI

 

 

0.95

0.79, 1.02

 

 

0.99

0.94, 1.04

Leg pain with NRI

 

 

0.78

0.65, 0.94

 

 

0.83

0.66, 1.06

Results reported with unstandardized beta coefficients and 95% confidence intervals unless otherwise indicated. For outcomes, a linear regression model is used unless: odds ratios from multinomial logistic model; beta coefficients from Tobit model; beta coefficients from gamma generalized linear model; 4 incident rate ratios from Poisson model. Adjusted models include sex, age, and body mass index. Est. = parameter estimates; CI = confidence interval; % MCSA = proportion of peak muscle cross-sectional area; LBP = low back pain; ROM = range of motion; NRI = nerve root involvement. Results with a significant difference from the reference are bolded.

 

Table 3: Associations between lowest % MCSA and outcomes.

 

      Univariable model

 

Adjusted model

Outcome

N

Est.

95%CI 

N

Est.

95%CI 

Symptom duration1 

<3 months

875

ref

ref

875

ref

ref

3 to 12 months

 

1.14

0.97, 1.33

 

1.15

0.94, 1.41

>12 months

 

1.26

1.07, 1.47

 

1.27

1.03, 1.55

LBP intensity

875

-0.06

-0.19, 0.06

875

-0.15

-0.31, 0.00

Leg pain intensity2

870

-0.30

-0.46, -0.14

870

-0.25

-0.46, -0.03

Low back disability

864

-0.69

-1.00, -0.38

864

-0.74

-1.14, -0.34

Morning stiffness1 

None

871

ref

ref

871

ref

ref

<30 minutes

 

1.06

0.90, 1.26

 

1.01

0.82, 1.26

30 to 60 minutes

 

1.04

0.89, 1.23

 

1.05

0.85, 1.31

>60 minutes

 

0.98

0.83, 1.15

 

0.92

0.75, 1.14

Physically strenuous work rating3

571

0.00

-0.01, 0.01

571

0.01

-0.01, 0.02

Directions with painful ROM (total)4

690

0.97

0.93, 1.01

690

0.99

0.93, 1.04

Leg pain and NRI signs1

No leg pain

769

ref

ref

769

ref

ref

Leg pain, no NRI

 

0.96

0.80, 1.14

 

1.01

0.97, 1.27

Leg pain with NRI

 

0.80

0.67, 0.96

 

0.87

0.69, 1.10










Results reported with unstandardized beta coefficients and 95% confidence intervals unless otherwise indicated. For outcomes, a linear regression model is used unless: odds ratios from multinomial logistic model; beta coefficients from Tobit model; beta coefficients from gamma generalized linear model; 4 incident rate ratios from Poisson model. Adjusted models include sex, age, and body mass index. Est. = parameter estimates; CI = confidence interval; % MCSA = proportion of peak muscle cross-sectional area; LBP = low back pain; ROM = range of motion; NRI = nerve root involvement. Results with a significant difference from the reference are bolded.

Discussion

This study sought to explore the associations between LMM quality, and clinical outcomes comprising patient-reported clinical and occupational information, and physical examination findings. We found consistent associations between the % MCSA of the LMM and low back-related disability and leg pain intensity, with marginally lower disability and leg pain ratings in patients with a higher proportion of pure muscle CSA. This means that, on average, patients with higher LMM quality reported lower levels of low back pain-related disability and leg pain intensity.

 

Our findings are consistent with results from several studies looking at low back disability using different measurement protocols, including different muscle measurements (total CSA of combined paraspinal muscles) [20], a composite pain/disability scale (Chronic Pain Grade Questionnaire) and muscle/fat grading system [22], and different imaging protocols (diagnostic ultrasound-measured LMM CSA and thickness) [19]. Arguments highlighting the potential reasons for a relationship between altered LMM size, structure, and/or function and reported low back disability appear plausible [19, 20]: the various causes of LMM atrophy or reduced functionality may also contribute to or exacerbate existing lower lumbar spine instability and/or limit physical movement. This could result in perceived or real disability in this region and in turn contribute to further LMM atrophy. However, this explanation remains controversial as several small to moderate population sample studies have reported no relationships between altered paraspinal muscle morphology and low back disability [18, 21, 23, 37].

 

On the other hand, previously published small population sample studies assessing the relationships between altered LMM morphology and leg pain intensity failed to identify any significant associations [38-40]. Therefore, the findings from this study appear to be the first to identify an inverse association that may exist between these two parameters. The most direct explanation for the limiting of this association to the lowest % MCSA category would be the presence of an underlying nerve root compromise which concurrently results in leg pain and isolated muscle quality reduction. While we did initially find a lower proportion of pure muscle was associated with a higher likelihood of patients presenting with leg pain and NRI, this association did not remain after adjusting for confounders. Although an association between altered LMM morphology and radiculopathy was noted in some studies [28, 29], no similar associations were identified in several other studies [26, 27, 40]. 

 

Barker et al. [18] identified a positive association between the duration of back pain and reduced LMM quantity, whereas we noted a small, positive association between pain duration and increased LMM quality. This appears to be a counterintuitive result, with no clear explanation as to why patients with higher paraspinal muscle quality would have a longer pain history. While muscle compensation from hyperactivity related to chronic pain is a possible explanation, this finding is more likely to be spurious than physiologic in nature.  

 

The absence of association we noted between LMM quality and LBP intensity was consistent with some studies [18, 20, 37], but not with others [19, 22]. Finally, we identified a lack of association between muscle quality and the physically strenuous nature of work, consistent with that reported by Fortin et al. [25]. We had postulated that reduced LMM quality may limit a person’s ability to perform more physically demanding work, or that more time spent performing less demanding work may reduce LMM quality; however, our findings indicated such an association is unlikely to exist.

 

Several strengths and limitations of this study are acknowledged. We had access to a large patient population referred for low back and/or leg pain treatment, which allowed for more in-depth analysis of multiple clinical variables in a clinically relevant cohort. However, as all patients were symptomatic, comparison with a healthy population was not possible. Even though this study did identify some significant associations, they were relatively weak in scale. While we identified each additional 10% of pure LMM CSA being associated with a 0.7 point lower RMDQ score, or a 0.3 point lower NRS leg pain score, the reported minimal clinically important difference (MCID) values for the disability and pain instruments we used are at least 2.0 and 1.0 points, respectively [34]. As such, the clinical importance or meaningfulness of these associations may be limited. Additionally, the conflicting results between studies make true comparisons challenging. It is likely some of these apparent conflicts are arising from the different populations being assessed, although the numerous variations in muscle measurement protocols are likely to be an additional contributing factor. To reduce the potential for selection bias and provide a more representative spectrum of low back or leg pain patient presentations across all age groups, we did not exclude patients with degenerative pathologies commonly found in a non-specific LBP population. The presence of these co-morbidities had the potential to impact on the final outcomes; however, as the degree of impact is unknown, future cross-sectional and/or longitudinal studies could be directed at investigating any associations between combined clinical and pathological variables and the paraspinal muscles. Although the data collection process did not lend itself to the identification of potential systemic neurological or myopathic disorders, patients included in this study presented to the Spine Centre with a primary complaint related to the low back. This should essentially have excluded systemic neuromusculoskeletal conditions significant enough to affect our findings. Lastly, this study used several self-reported outcomes, relying on patient recall and interpretation. While objective, validated NPS and RMDQ measures were implemented where possible [33, 34], other measures, such as time since onset of pain, timing of morning stiffness, and strenuous nature of work, were more subjective in nature.

Conclusion

The findings from this study support the hypothesis of an association between altered LMM morphology and clinical measures, specifically showing a greater proportion of pure LMM being associated with lower low back disability and leg pain intensity, but longer time since pain onset. The clinical importance of these findings is questionable, though, due to weak associations for all three outcomes. No associations were noted with the remaining clinical measures after adjusting for cofounders. As the presence of various co-morbidities may have impacted on the clinical measures, further investigation into the potentially complex interactions between clinical measures, spinal pathology, and multifidus muscle quality should be pursued to clarify the level of influence these may have on each other, and how this might relate to clinical outcomes or guide the management of patients with lumbar-related pain.

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Declarations

Acknowledgements

The authors are very grateful for the guiding input Prof Bruce Walker, OAM, provided in the initial development and planning of this study.

 

Competing interests

AJ received a consulting fee from Murdoch University. JH received institutional research support from the New Brunswick Health Research Foundation and the Canadian Chiropractic Research Foundation. TJ received institutional grant support from the Foundation for Chiropractic Research and Post Graduate Education. The remaining authors declare that they have no competing interests.