Fatty infiltration of multifidus muscle independently increases osteoporotic vertebral compression fracture risk 

DOI: https://doi.org/10.21203/rs.3.rs-2060773/v1

Abstract

Background

Vertebral compression fractures decrease daily life activities and increase economic and social burdens. In addition, sarcopenia and back muscle atrophy influence osteoporotic vertebral compression fractures (OVCF). Therefore, this study aimed to evaluate the influence of the multifidus muscle on the OVCF.

Methods

We retrospectively recruited the study population based on the hospital database following the inclusion and exclusion criteria. The inclusion criteria were: 1) ≥ 60 years and 2) concurrent bone mineral density (BMD) and lumbar spine magnetic resonance imaging (MRI). The exclusion criteria were: 1) a history of lumbar spinal surgery, 2) lumbar spine metastasis, and 3) systemic diseases affecting bone density, including chronic renal failure and liver cirrhosis. The participants were divided into three groups based on lumbar spine BMD and OVCF. The control group underwent BMD and spinal MRI evaluation but not OVCF. Based on the T-score of lumbar spine BMD, the fracture groups with OVCF were divided into osteopenia and osteoporosis groups. Osteopenia BMD groups showed osteopenia T-scores of spinal BMD of over − 2.5. Osteoporosis BMD groups also showed osteoporosis T-scores of lumbar BMD of -2.5 and below.

Results

We included 120 patients who had visited our hospital. Based on spinal MRI, 75 participants were diagnosed with OVCF, and 45 were not. Age, BMD, and the psoas index significantly differed between the control and fracture groups. Moreover, fatty infiltration of the multifidus muscle indifferently affected the OVCF, with and without adjusting for other significant factors.

Conclusions

The severity of fatty infiltration of the multifidus muscle increases the risk of a spinal fracture. Therefore, preserving the quality of the spinal muscle and bone density is essential for preventing OVCF.

Background

Vertebral compression fractures decrease daily life activities and increase economic and social burdens.1 Ageing process decreases bone mineral density (BMD) and bone quality of the spine, which increases the incidence of osteoporotic vertebral compression fracture (OVCF). Therefore, early diagnosis and treatment of spinal osteoporosis can decrease the risk of OVCF.2

Clinically, spinal BMD measurement is the principal diagnostic tool for spinal osteoporosis. A decreased BMD increases the risk of OVCF. A T-score of BMD < -2.5 has been regarded as the limit for osteoporosis treatment. However, when the T-score of BMD is over − 2.5, OVCF can occur. Factors other than BMD can affect spinal compression fractures.3

Sarcopenia has been a noticeable factor in the aging health problem.4 Declined functional performance due to decreased muscle mass and strength also decreases the quality of life. Currently, researchers are paying attention to the interconnection and bidirectional influence between muscle and bone metabolism.5 Muscle strain influences bone metabolism through osteocytes. Moreover, the multifidus muscle stabilizes the segmental spine to prepare for movement. If dynamic stabilization following the load on the segmental spine deteriorates, a force can be focused on the focal area of the segmental spine or a single level of the spine.6, 7 Focused force on the spine during activity can increase the vulnerability of OVCF to aging.

Therefore, we aimed to evaluate the extent to which the quality and quantity of the multifidus muscle affect OVCF in individuals aged > 60 years.

Methods

Study population

The study population was retrospectively recruited from patients who visited the hospital between January 2020 and April 2022. The institutional review board (YUMC 2022-08-045) approved this study and waived the requirement for informed consent. In addition, this study recruited data based on the hospital database following the inclusion and exclusion criteria. The inclusion criteria were: 1) ≥ 60 years and 2) concurrent BMD and lumbar spine magnetic resonance imaging (MRI). The exclusion criteria were: 1) history of lumbar spinal surgery, 2) cancer, 3) spine infection, and 4) severe degenerative scoliosis.

The participants were divided into three groups based on lumbar spine BMD and OVCF. The control group underwent BMD and spinal MRI evaluation but not OVCF. Based on the T-score of lumbar spine BMD, the fracture groups with OVCF were divided into osteopenia and osteoporosis groups. Osteopenia BMD groups (P-BMD) showed osteopenia T-scores of spinal BMD of over -2.5. Osteoporosis BMD groups (O-BMD) also showed osteoporosis T-scores of lumbar BMD of -2.5 and below.

Multifidus measurement using spine MRI 

FIJI software (http://fiji. sc/Fiji) was used for quantitative analysis. Semi-automated methods using FIJI software measured the cross-sectional area (CSA) of the psoas and multifidus muscles in the same manner as in a previous study. The CSA of the psoas muscle was measured at the L3 level. (Figure 1. A) The Psoas index was calculated by dividing the CSA of both sides by height squared (m2). The CSA of the multifidus muscle was manually measured using T2-weight axial spinal MRI. (Figure 1. B) The fat area of the multifidus muscle was determined using the threshold analysis. (Figure 1. C) The optimal threshold for fat tissue was manually determined. The percentage of muscle fibers in the multifidus muscle (PMF) was calculated by subtracting the fat area from the CSA and multiplying it by 100.

Statistical analyses

Variants between the control and fracture groups were analyzed using a t-test. Analysis of variance (ANOVA) was used to evaluate whether there were differences in age, body mass index (BMI), bone density, and muscle components among the groups (control, P-BMD, and O-BMD). A post hoc test was conducted to analyze significant differences among the groups. The percentage of muscle mass excluding fat tissue in CSA of the multifidus muscle (PMM) between the fracture and lower lumbar level was evaluated using a paired t-test to determine whether there was a significant difference. Multivariate logistic regression analysis was used to evaluate the effect of PMF on OVCF, with and without adjustment for bone density, age, and BMI. Statistical significance was set at p < 0.05.

Results

We included 120 patients who had visited our hospital. (Table 1) Based on spine MRI, 75 participants were diagnosed with OVCF, and 45 were not. Age, bone density, and psoas index differed significantly between the control and fracture groups. While the CSA of the multifidus muscle did not show a significant difference, the PMF showed a significant difference between the control and fracture groups. The control group had more muscle fibers than the fracture group. Fatty infiltration of the multifidus muscle was higher in the fracture group than in the control group.

Table 1

Demographic data and analysis of variance according to the groups
 

Total

(n = 120)

Control group (n = 45)

Fracture group

P value

P-BMD

O-BMD

Age (year)

72.79 ± 7.58

69.86 ± 5.6 1)

74.54 ± 8.06

0.00*

72.92 ± 7.95(1), (2)

76.50 ± 7.87 (2)

0.00*

BMI (kg/m2)

23.49 ± 3.42

24.53 ± 3.44 (1)

22.87 ± 3.28

0.09

24.02 ± 2.94 (1)

21.47 ± 3.16 (2)

0.00*

Bone density (g/cm2)

0.80 ± 0.16

0.90 ± 0.14 (1)

0.74 ± 0.14

0.00*

0.82 ± 0.12 (2)

0.63 ± 0.08 (3)

0.00*

Psoas index (cm2/m2)

4.91 ± 1.21

5.21 ± 1.13 (1)

4.72 ± 1.23

0.03*

4.93 ± 1.25(1), (2)

4.48 ± 1.17 (2)

0.02*

Multifidus on L4-5

CSA

(mm2)

1246.19 ± 346.29

1199.65 ± 380.44

1274 ± 323.53

0.25

1212.41 ± 289.18

1348.50 ± 350.60

0.12

PMF (%)

61.69 ± 17.24

74.89 ± 10.20 (1)

53.78 ± 15.71

0.00*

47.06 ± 13.25 (2)

45.20 ± 18.40 (2)

0.00*

Multifidus on L5-S1

CSA

(mm2)

1351.95 ± 358.18

1311.09 ± 341.07

1376.47 ± 368.13

0.33

1400.47 ± 337.55

1347.52 ± 405.22

0.51

PMF (%)

61.85 ± 14.39

70.12 ± 12.36(1)

56.89 ± 13.25

0.00*
 

55.12 ± 12.70 (2)

59.03 ± 13.77(2)

0.00*

Fractur Level

(Numbur of patients)

T10

2

1

1

  

T11

6

4

2

  

T12

14

3

11

  

L1

23

8

15

  

L2

8

3

5

  

L3

8

4

4

  

L4

9

3

6

  

L5

5

3

2

  
The significance level was set at P < 0.05. * Significant differences were determined using analysis of variance. Among the groups, means (with different superscript numbers) are statistically significantly different according to Tukey’s post hoc test. PMF: Percentage of muscle fibers in the multifidus muscle.


Age, bone density, BMI, and psoas index showed significant differences among the control, P-BMD, and O-BMD groups. In contrast, the CSA of the multifidus muscles did not show significant differences among the groups. In addition, the mean CSA of the multifidus muscles was higher in the fracture group than in the control group. The control and fracture groups (P-BMD and O-BMD) showed significant differences in the percentage of muscle fiber in the multifidus muscle. Furthermore, the fracture group showed lower functional muscle mass than the control group.

PMM at L4-5 and L5-S1 but not CSA of the multifidus muscle significantly influence the OVCF, with or without adjusting for age, BMI, bone mineral, and psoas index. (Table 2) Fatty degeneration of the multifidus muscle showed a positive relationship with spinal compression fractures. The PMM between the fracture and lower lumbar levels did not significantly differ. (Fig. 2)

Table 2

Multivariate logistic regression analysis for the osteoporotic compression fracture risk according to quantity and quality of multifidus muscles

Variables

Fracture Risk

Crude

Adjusted

OR (95% CI)

P

ORⱡ (95% CI)

P

CSA of multifidus

on L4-5

1.00 (1.00, 1.00)

0.25

1.00 (0.99, 1.00)

1.00

on L5-1

1.00 (0.99, 1.00)

0.33

1.10 (0.81, 1.18)

0.10

PMM

on L4-5

0.88 (0.84, 0.92)

0.00*

0.87 (0.82, 0.92)

0.00*

on L5-1

0.92 (0.89, 0.95)

0.00*

0.91 (0.88, 0.95)

0.00*
OR, odds ratio; CI, confidence interval; CSA, cross-sectional area; PMM, percentage of muscle mass excluding fat tissue in CSA of the multifidus muscle
* P < 0.05
ⱡ Adjusted for age, body mass index, Bone mineral density, and psoas index.

Discussion

Age and bone density significantly affect the incidence of OVCF. As a surrogate of systemic muscle mass, a decreased psoas index also affects OVCF. The CSA of the multifidus muscle did not show a relationship with the incidence of OVCF. However, fatty infiltration of the multifidus muscle affected the OVCF. An increase in fatty infiltration of the multifidus muscle significantly affected OVCF, with and without adjusting for other factors. Furthermore, the severity of fatty infiltration of the multifidus muscle increased the risk of spinal fracture, even though the T-score of BMD indicated osteopenia. Therefore, preserving spinal muscle quality and bone density is essential for preventing OVCF.

Clinically, BMD evaluation provides a guideline for osteopenia and osteoporosis diagnoses.8, 9 A T-score below − 2.5 in BMD has been the gold standard for osteoporosis treatment guidelines. Low BMD increases the risk of bone fracture. However, the T-score of the BMD was not a decisive factor for spinal fractures. Sometimes, there was compression fracture in patients with a T-score higher than − 2.5 in BMD. BMD and other multifactorial factors affect osteoporotic fractures. Multifactorial factors include bone quality, muscle component, social factors, and comorbidity factors.10–12 In patients with chronic kidney disease, BMD showed a relationship with spine osteoporotic fracture risk.13 BMD can assess the macro scale of bone. However, the nanoscale of bone tissue, which has microarchitecture and tissue properties, can influence bone strength and fragility.14 Among these, sarcopenia has received attention as a potential factor influencing osteoporotic fracture, with its increase in the aging population.15 Therefore, researchers have tried to elucidate the components affecting spinal compression fractures associated with frailty and aging.

The multifidus muscle enhances the stabilization of the spine.16 Multifidus muscles have a short extending length, so muscle fibers are packed densely within a small volume. The muscle fibers’ high stiffness increases the resistance of lumbar spine flexion. Therefore, the lumbar back muscle atrophy increases compression and shear force within the disc level.17 The patients who underwent OVCF showed a significant increase in spinal flexion load than those without OVCF.18 Therefore, multifidus muscle atrophy increases the flexion force and decreases the spinal segment stability, resulting in an increased risk of OVCF. However, in this study, the CSA of the multifidus muscle did not show significant differences among the groups, not even between the fracture and control groups. In addition, fatty infiltration of the multifidus muscle significantly affected the OVCF. As atrophy of the back muscles is generally present in elderly patients, preserving muscle fibers is directly correlated with muscle function. Along with muscle atrophy, fatty infiltration of the skeletal muscle (myosteatosis) is also an essential frailty process.19, 20 Therefore, we presume that PMF but not CSA is a more accurate factor for OVCF.

Sarcopenia is a generalized muscle disorder, including low muscle strength, low muscle quantity, and low physical performance.21 Systemic muscle atrophy can influence the atrophy of localized spinal muscle mass and function, increasing the incidence of a spinal fracture.22, 23 This is because core muscles stabilize the spinal segment. However, this hypothesis remains controversial. Furthermore, some studies reported that the psoas index and/or back muscle atrophy were not independent risk factors for spinal compression fracture.24, 25 This discrepancy might be due to a simple error in measuring CSA without considering a fatty change. We reported that PMF but not CSA of the multifidus muscle was an independent risk factor for OVCF.

Identifying the factors associated with OVCF is essential for preventing further fractures. The T-score of BMD is a robust and quantitative predictive factor for osteoporotic fracture risk.26 However, it should be considered that the T-score sometimes shows discordance with osteoporotic fracture risk. Degenerated lumbar spine showed uncertainty for BMD measurement for aging.27 Measurement of bone density can be affected by calcifying structures around the spine, which are anterior and posterior longitudinal ligament, ligament flavum, aorta, and interspinous ligament.28, 29 Therefore, prediction of fracture risk is a challenge concerning the degenerative spine. The PMF in the P-BMD group significantly decreased than that in the control group. Back muscle quality had a significant impact on OVCF independent of BMD. This study showed that preserving muscle quality is essential for preventing compression fractures in the elderly.

This study has some limitations. First, we did not analyze the entire area of the back muscles. We only used the L4-5 and L5-S1 levels as surrogates of the back muscles to compare the control and fracture groups with various fracture sites. However, there was no significant difference between the PMF at the fracture and lower lumbar levels. In a previous study, back muscle degeneration was correlated with aging. Therefore, the analysis of the multifidus muscle in the lower lumbar region can represent the degree of systemic back muscle degeneration.

Conclusions

Fatty infiltration of the back muscle significantly affects OVCF in the elderly, independent of BMD. Therefore, physicians should pay attention to the state of the back muscles in the elderly to prevent compression fractures.

Abbreviations

OVCF, osteoporotic vertebral compression fracture; BMD, bone mineral density; P-BMD, osteopenia BMD; O-BMD, osteoporosis BMD; CSA, cross-sectional area; PMF, percentage of muscle fibers in the multifidus muscle; MRI: magnetic resonance imaging.

Declarations

Ethics approval and consent to participate: The study was conducted in accordance with the Declaration of Helsinki guidelines and approved by the Institutional Review Board of Yeungnam University Medical Center (protocol codes 0000 2022-08-045). The need for patient consent was waived by the Institutional Review Board of Yeungnam University Medical Center (protocol codes 0000 2022-08-045), due to the retrospective nature of this study.

Consent for publication: Not applicable

Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Competing interests: The authors declare no conflict of interest. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit on the authors or on any organization with which the authors are associated.

Funding: This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) and funded by the Ministry of Education (2022R1I1A3071887).

Authors’ contributions: Conceptualization, DG Lee; methodology, JH Bae; formal analysis and data curation, DG Lee; investigation, JH Bae; writing—original draft preparation, DG Lee; writing—review and editing, JH Bae; visualization, DG Lee; supervision, JH Bae; and funding acquisition, DG Lee

Acknowledgements: Not applicable

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