*2.3. Outcome Measures*

Other demographic factors that may be associated with functional disability in ADL, including age, sex, comorbid disease, radiologic severity of LSS (degree of stenosis and number of stenotic segment) and duration of symptoms, were also evaluated. The degree of spinal canal stenosis was categorized from A to D, according to the previous method of classification by Schizas et al. [18] using MRI. That of foraminal stenosis was categorized as mild, moderate or severe stenosis.

We also measured the cross-sectional area (CSA) of the psoas and multifidus muscles, using T1-weighted axial MRI images at the midpoint of the L3/4 intervertebral disc. Using picture archiving and communication system imaging measurement software (Infinitt healthcare, Seoul, Republic of Korea), the CSA of the multifidus and the psoas muscles were measured, as presented in Figure 1. All measurements were independently analyzed by two pain physicians who were blinded to patients' characteristics, and a consensus had to be found. In case of disagreement with a difference of more than 15%, images were reviewed together and discussed until the consensus was gained.

**Figure 1.** A representative magnetic resonance image for the measurement of cross-sectional area (mm2) of the psoas and multifidus muscles. P, psoas muscle; M, multifidus muscle.

#### *2.4. Epidural Steroid Injection Procedure*

All participants received a target-specific transforaminal epidural steroid injection in the involved spinal segment judged from the patients' symptoms and MRI findings at their first visits. All procedures were performed with guidance with a fluoroscope (ARCADIS Orbic®; Siemens AG, Erlangen, Germany) by an experienced pain physician. The patients were placed in a prone position, and standard sterile preparation was conducted. Using the ipsilateral oblique view on the fluoroscopy to obtain a traditional "safety triangle" image [19], a 22-gauge spinal needle was introduced just inferior to the pedicle using the tunnel vision technique. After reaching the intervertebral foramen, the final position of the needle tip was adjusted using the anteroposterior and lateral fluoroscopic view. After confirming appropriate epidural contrast uptake, 5 mL of 0.6 % lidocaine containing 5 mg dexamethasone was administered. For the multi-level procedure at two or more sites, 5 mL

of drug was used at each level, with a divided dose of dexamethasone not to exceed a total dose of 5 mg. The number of epidural blocks during 4 weeks and the degree of pain relief using the changes of NRS at the first visit and 4-weeks follow-up were recorded.

The body composition parameters, including body fat mass (kg), percent body fat (%), skeletal muscle mass (kg), skeletal muscle index (kg/m2) and other demographic characteristics, were compared between the mild/moderate and severe disability groups. The primary outcomes were the differences of the body composition parameters between the two groups. Secondary outcomes included epidural block-related therapeutic effects in the two groups.

#### *2.5. Sample Size Determination and Statistical Analysis*

Sample size was predetermined by the *t*-test sample size calculation, using IBM SPSS Statistics for Windows, version 27, based on the assumption that the minimum detectable difference between the two groups in percent body fat was 10%. A total of 64 patients were required, with a significance level of 0.05 (α = 0.05) and a power of 80% (β = 0.20). Considering the predicted dropout rate, the total sample size was increased to 72.

All descriptive data are expressed as the number of patients, mean ± SD, and median [interquartile range]. Continuous variables were analyzed by a two-tailed *t*-test or Mann—Whitney rank-sum test after a normality test. The χ<sup>2</sup> test was used to compare categorical variables. Linear regression analysis was performed to verify the relationships between body composition parameters and the ODI scores. A *p*-value of less than 0.05 was considered statistically significant. All statistical analyses were performed using IBM SPSS Statistics for Windows, version 27.

#### **3. Results**

### *3.1. Study Participants and Patient Characteristics*

Among the 72 participants enrolled, 63 patients (29 in the mild/moderate group and 34 in the severe disability group) completed the study. The CONSORT flow diagram is shown in Figure 2. The average ODI score was 26.9 and 55.6 in the mild/moderate and severe disability groups, respectively (*p* < 0.001). Patient demographics, including age, sex, body weight, body mass index (BMI) and radiologic severity of LSS, were compared between the two groups. No significant differences of these parameters were observed between the two groups (Table 1).

**Figure 2.** Subject flow diagram.


#### **Table 1.** Patient demographics.

Data are presented as median (interquartile range), numbers, mean ± standard deviations, or numbers (percentages). Mild/moderate disability was defined as Oswestry disability score (ODI) ≤40. Severe disability was ODI > 40. \* *p* < 0.05 by two-tailed *t*-test.

#### *3.2. Study Outcomes*

Body composition parameters and cross-sectional areas of the spinal muscles of the two groups are shown in Table 2. Percent body fat (%) was significantly higher in the severe disability group compared to the mild/moderate group in each sex (*p* = 0.016 in male and *p* = 0.004 in female). The proportion of obese patients (percent body fat ≥17% in men and ≥32 % in women) was compared, and it was significantly higher in the severe disability group compared to the mild/moderate group only in females (*p* = 0.028 by chi-square test).

**Table 2.** Body composition parameters by bioimpedance analysis and cross-sectional areas of the psoas and multifidus muscles.



Data are presented as numbers, means ± standard deviations and median (interquartile range). BMI, body mass index; CSA, cross-sectional area. \* *p* < 0.05 by two-tailed *t*-test. † Obese patients were judged from percent body fat ≥ 32% in women and ≥17% in men. ‡ *<sup>p</sup>* < 0.05 by Chi-square test. § *<sup>p</sup>* < 0.05 by Mann–Whitney rank-sum test.

The linear regression analysis revealed that percent body fat was positively correlated to the ODI score in males (r = 0.554 and *p* = 0.005). However, there was no statistically significant relationship between them in females (r = 0.331 and *p* = 0.052) (Figure 3).

**Figure 3.** Relationships between percent body fat (%) and Oswestry disability index score.

Meanwhile, there were no significant differences in the body composition parameters related to skeletal muscle, including skeletal muscle mass (kg) and skeletal muscle index (kg/m2), between the two groups. However, the CSA of the spinal muscles, such as psoas and multifidus, were significantly different between the two groups in each sex. The CSAs of psoas muscles were significantly smaller in the severe disability groups compared to the mild/moderate group in each sex (*p* < 0.001 in male and *p* = 0.020 in female) (Table 2). In further analysis, there were significant linear relationships between the CSA of psoas and multifidus muscles and the ODI score (Figure 4A,B).

**Figure 4.** Relationships between cross-sectional area (CSA) of psoas and multifidus muscles (mm2) and Oswestry disability index score.

The epidural block procedure-related pain-relieving effect is shown in Table 3. The NRS score at 4 weeks following the first epidural block was significantly lower in the mild/moderate disability group compared to the severe disability group (*p* < 0.001). The patients in the severe disability group experienced a smaller pain-relieving effect from the epidural block compared to the mild/moderate disability group (45.1% vs. 25.2%, *p* = 0.002).

**Table 3.** Epidural block-related profile.


NRS, Numeric rating scale. \* *p* < 0.05 by Mann–Whitney rank-sum test. † *p* < 0.05 by two-tailed *t*-test.

#### **4. Discussion**

The current study demonstrated that LSS patients with severe disability in ADL (ODI score > 40) had a significantly higher fat mass and percent body fat compared to subjects with mild to moderate disability. The higher the percentage of body fat, the greater the functional disability in ADL, with a linear relationship. As previous studies suggested that radiologic imaging is limited for evaluating disease severity [5,6], radiologic severity of LSS was comparable between the mild/moderate and severe disability groups in this study. Meanwhile, LSS patients with severe disability experienced a smaller therapeutic effect from repeated epidural blocks compared to those with mild/moderate disability. This result suggests that evaluating functional disability in LSS patients potentially helps to predict the response to conservative treatment, such as epidural blocks, and to establish more effective treatment options promptly. Many studies suggested that overweight and obesity was positively related to the development of lumbar spinal diseases [10–13]. However, the precise mechanisms of the association are little known, and the causal relationships are also unclear. Some studies believe that excessive mechanical overload might affect the development of degenerative spinal disease [10,12]. Others suggests that obesity might be the result of the limited daily activity caused by spinal pain [20]. Despite numerous studies, there are few investigations of how obesity affects functional disability in patients who were diagnosed with LSS.

Fanuele et al. revealed that general and spinal disease-associated functional status was significantly worse in overweight and obese patients compared to normal weight individuals in a large population-based cross-sectional survey [21]. However, they declared the possible inaccuracy of self-reported BMI as one of the limitations of the study. BMI is a commonly used tool for clarifying obesity in most studies [8,10,11,14,21]. It is a simple, traditional and easily applicable method to judge body fatness in clinical practice. However, BMI, which is body weight in kilograms divided by height in meters squared, is not the accurate measurement of body fat. It cannot distinguish between body fat and lean body mass nor reflect accurate body fat mass and distribution. BMI might overor underestimate body fat, and it can be different according to sex, age, ethnicity and individual variations [22,23].

The current study proved that percent body fat was a better predictor for functional disability in LSS patients than BMI was, even though the mechanism of association between percent body fat and functional disability in ADL in LSS patients remains unclear. Although percent body fat was significantly different between the mild/moderate and severe disability group, the BMI was similar in the two groups. Therefore, we suggest that the body composition analysis could be used as a part of a supplementary diagnostic tool for predicting the functional status of LSS patients in clinical practice. BIA is a reliable, inexpensive, fast and bed-side applicable tool for measuring body composition. It allows estimating the composition of various body compartments, such as body fat, fat-free mass, body water or body cell mass in both healthy and ill subjects [24–26]. BIA has also been recently applied to evaluate nutritional or metabolic status, as well as body hydration

status, in patients with various entities of diseases [27]. BIA might be able to expand its role for predicting the severity or the prognosis of various painful musculoskeletal disorders, and further investigations in a large population should be performed.

The current study also aimed to evaluate whether the severe disability of LSS patients was associated with the skeletal muscle parameters of BIA, such as skeletal muscle mass or index. However, we cannot find those associations. Indeed, sarcopenia has been focused on as associated with decreased function in ADL in older patients, with further association with several musculoskeletal disease entities [28]. Furthermore, the importance of the paraspinal muscle has been investigated in the clinical progress of various musculoskeletal diseases of the lumbar spine. Structural change, such as atrophy or fat infiltration in the multifidus and paraspinal muscles, has been observed in patients with chronic low back pain [28–31]. In the current study, skeletal muscle parameters of BIA were not beneficial enough for predicting the functional disability of LSS patients, but radiologic measures of psoas and multifidus muscles seem to have the potential to predict it. A future study of a large population should be performed to explain these associations clearly.

These are limitations of this study. First, this study was limited to a relatively small number of participants of a single hospital. Second, the causality of the patients' LSS and their body composition characteristics were not discussed. Third, the long-term effect of high percent body fat or reduction of body fat on LSS was not evaluated in this study. The effects of physical or surgical weight reduction on the improvement of patients' symptoms and function are still inconclusive [32,33]. Further observational cohort studies can be conducted.
