Combined impact of lifestyle factors on low back pain: A cross-sectional study of over 400,000 Japanese adults

Background: Many epidemiological studies have indicated the association between low back pain (LBP) and lifestyle factors, such as physical activity, smoking, weight gain, diet, and sleep problems. However, the combined effect of lifestyle factors on LBP has not been adequately investigated. Thus, we aimed to investigate the association between a cluster of unhealthy lifestyle behaviors and LBP using a large cohort of Japanese adults. Methods: We included 419,003 adults aged over 20 years who underwent an annual health checkup between April 2013 and March 2014 in Japan. Information on the following lifestyle factors were collected using the standardized questionnaire recommended by the Ministry of Health, Labour and Welfare in Japan: smoking, alcohol intake, exercise, physical activity, walking speed, weight control, eating habits, and sleep. Each factor was evaluated as a dichotomous variable (1: health risk, 0: no health risk). A lifestyle risk score was calculated by summing the score of each lifestyle factor (range: 0-12) and was categorized into three groups (low, moderate, high). LBP was defined as self-reported LBP under treatment. Logistic regression analysis was conducted to calculate the odds ratio (OR) and 95% confidence interval (CI) for LBP. Results: In multivariate logistic regression analysis, the OR for LBP was significantly higher in the moderate risk score group (adjusted OR: 1.33 [95% CI: 1.23-1.44] in men; 1.40 [95% CI: 1.27-1.54] in women) and the high risk score group (adjusted OR: 1.54 [95% CI: 1.43-1.67] in men; 1.83 [95% CI: 1.64-2.03] in women) than in the low risk score group. A trend of higher risk of LBP associated with higher lifestyle risk score was observed in both sexes ( p for trend < 0.001). These results were similar even in subgroup analysis by age (20-39, 40-59, and ≥ 60 years) and body mass index (BMI) (< 18.5, 18.5-24.9, and ≥ 25 kg/m 2 ).

domain as they are potentially modifiable. In fact, targeting lifestyle as part of the management of LBP has been recommended [4,5].
The impact of lifestyle factors such as smoking, physical activity, alcohol, and diet on health outcome has been extensively studied. This impact, mainly on cardiovascular disease [6], diabetes [7], cancer [8], and mortality [9], has been shown to be especially greater when the factors were accumulated. Therefore, evaluating the cluster of lifestyle factors is considered important to prevent the negative effects on health.
The development and chronicity of LBP have been considered to be linked to lifestyle factors. A population-based study using data from National Health and Nutrition Examination Survey indicated that smoking, physical activity, and obesity were associated with LBP [10]. Similarly, many studies investigated the association of LBP with each lifestyle factor such as smoking, physical inactivity, alcohol consumption, and sleep disturbance [11][12][13][14]. However, the combined effects of lifestyle risk factors on LBP have not been adequately investigated. Elucidating the effect of the accumulation of lifestyle factors on LBP may help to demonstrate the importance of lifestyle modification for the prevention or management of LBP. Therefore, we aimed to investigate the combined effects of multiple lifestyle factors on LBP using a large-scale data in Japan. We hypothesized that the accumulation of unhealthy lifestyle factors is associated with increased LBP because lifestyle behaviors consist of multiple dimensions that coexist and are mutually related in many cases [15,16].

Study population
This was a cross-sectional study that used health checkup data. The check-up was conducted by the All Japan Labor Welfare Foundation, a health checkup center in Japan. Subjects in the present study were adults aged over 20 years who underwent the annual health checkup between April 2013 and March 2014. Of the 552,005 subjects, 551,871 subjects consented to participate in this study. Of these, we excluded 132,868 subjects with missing data on any variables used in the present study.
Thus, 419,003 participants were included in the analysis. Written informed consent for the use of personal health checkup data in this study was obtained from each participant. This study protocol was approved by the Ethics Committee of the All Japan Labor Welfare Foundation (Approval No. 9-1-0007) and the medical ethics committee of Showa University School of Medicine (Approval No. 2407).

Study measures
Data on age, sex, lifestyle behaviors, medical history, and current use of medications were collected using a self-administered questionnaire. Trained staff measured height to the nearest 0.1 cm using a stadiometer and weight to the nearest 0.1 kg using a scale. Body mass index (BMI) was calculated as weight (kg) divided by the square of height (m). Blood pressure was measured in the sitting position using an automated sphygmomanometer (HEM-907, Omron, Kyoto, Japan). LBP was defined as selfreported LBP under treatment (i.e., a "yes" answer to the question "Do you have LBP under treatment including follow-up?") [17].
Blood samples were collected and stored in a cooler at 4°C for transporting to an external laboratory (SRL, Tokyo, Japan). Triglyceride levels were measured using an enzymatic method (AU5400; Beckman Coulter, Tokyo, Japan), while low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured using a direct method (AU5400; Beckman Coulter, Tokyo, Japan). Hemoglobin A1c (HbA1c) level was determined using latex agglutination turbidimetry (JCA-BM9130, JEOL, Tokyo, Japan).

Assessment of lifestyle risk score
Questionnaire items on lifestyle behaviors were based on the standardized questionnaire used for the National Health Promotion Program [21,22], which started in Japan in 2008 and aimed to prevent lifestyle-related diseases (e.g., metabolic syndrome and cardiovascular disease). The following 12 items related to lifestyle behaviors were used in the present study: 1) smoking habits (current, former, none), 2) alcohol intake (everyday, sometimes, none), 3) exercise ≥ 30 min/day, ≥ twice a week, and ≥ 1 year (yes, no), 4) physical activity equal to walking ≥ 60 min/day (yes, no), 5) walking faster than others in the same generation (yes, no), 6) weight gain ≥ 10 kg since age 20 years (yes, no), 7) body weight change ≥ 3 kg during the preceding 1 year (yes, no), 8) eating speed (fast, normal, slow), 9) eating dinner within 2 hours before bed ≥ three times per week (yes, no), 10) having a snack after dinner ≥ three times per week (yes, no), 11) skipping breakfast ≥ three times per week (yes, no), and 12) adequate sleeping (yes, no).

Statistical analysis
Data on the participants' characteristics are presented as n (%) or median (25th, 75th percentile).
Characteristics of the study participants with and without LBP were compared using chi-squared test for categorical variables or Wilcoxon rank-sum test for continuous variables.
To evaluate the association between LBP and lifestyle risk levels, a logistic regression analysis was performed to calculate the odds ratio (OR) and 95% confidence interval (CI) for LBP. Model 1 was a crude model, and model 2 was adjusted for age and BMI. Model 3 was further adjusted for hypertension, diabetes, and dyslipidemia. We then examined the association between LBP and lifestyle risk score stratified by age (20-39, 40-59, and ≥ 60 years) and BMI (underweight: < 18.5, normal weight: 18.5-24.9, and overweight/obesity: ≥ 25 kg/m 2 ) categories in model 3. Test for trend was conducted with the lifestyle risk score groups considered as continuous variables. All statistical analyses were performed using SAS software version 9.4 (SAS Institute Inc., Cary, NC, USA). A p value < 0.05 was considered statistically significant.

Results
The median age (25th, 75th percentile) of the study participants was 45 (range, 36, 55) years, and 67.1% of the participants were men. Comparison of the participants' characteristics according to LBP is shown in Table 1 for men and Table 2 for women. Individuals with LBP were older, had higher BMI, and were more likely to have hypertension, diabetes, and dyslipidemia than those without LBP in both sexes. Table 3 shows the association between lifestyle risk score (low, moderate, and high) and LBP by sex.
In both sexes, the age-and BMI-adjusted OR for LBP were higher in the moderate risk score group  Table 4 shows the association between LBP and lifestyle risk score by age groups. In all age categories, compared to individuals with low risk score, the ORs for LBP in the moderate and the high risk score groups were significantly increased. A trend of higher risk of LBP associated with higher lifestyle risk score was observed in both sexes and all age groups (p for trend < 0.001 in all).
We also performed BMI-stratified analysis for the association between lifestyle risk score and LBP ( . Among subjects with normal weight or overweight/obesity, LBP was significantly associated with lifestyle risk score in the moderate risk score group and the high risk score group. There were significant dose-response relationships between the level of lifestyle risk score and LBP in all BMI strata (p for trend < 0.01 in all).

Discussion
Our study investigated the combined effects of multiple unhealthy lifestyle behaviors on LBP using a large-scale health checkup data in Japan. We found that a combination of unhealthy lifestyle behaviors was dose-dependently associated with increased LBP in both sexes. These associations were observed regardless of age and BMI status. To our knowledge, this is the first study demonstrating the influence of unhealthy lifestyle clustering, which included multifaceted lifestyle factors, on LBP in Japanese adults.
Many epidemiological studies have investigated the association between LBP and each lifestyle risk factor such as physical inactivity [13], smoking [14], exercise [30], alcohol [12], and sleep disturbance [31]. Focusing on the clustering of multiple lifestyle risk factors, we evaluated unhealthy lifestyle factors using 12 questionnaire items that have been recommended for use by the National Health Promotion Program in Japan [21,22]. These factors included Breslow's health habits including smoking, alcohol drinking, physical activity, weight control, breakfast, snacking, and sleep [32].
Previous studies that investigated the relationship between healthy lifestyle behaviors and LBP [33][34][35] indicated that health lifestyle behaviors may decrease the risk of developing LBP, although there may be sex-or age-related differences in the effects. It is difficult to directly compare our results with previous findings because the definition of health lifestyle behaviors varies by studies. For example, a previous study defined health behavior using information on BMI, physical exercise, and smoking [34].
However, our findings were consistent with those of previous studies. Our results that clustering of unhealthy lifestyles could negatively influence LBP may have important implications for the prevention and management of LBP both in a public health and a clinical perspective.
Age is one of the common risk factors for LBP. A previous systematic review has demonstrated that the prevalence of severe LBP increases with age [36]. Although several lifestyle behaviors were also expected to vary depending on age, our age-stratified analyses indicated the dose-response relationship between accumulation of unhealthy lifestyle risk and LBP regardless of age groups (20-39, 40-59, and ≥ 60 years). These findings suggest the importance of education related to healthy lifestyle for preventing LBP throughout the adult population.
Previous systematic reviews with meta-analysis have shown that overweight and obesity increased the risk of LBP [37,38]. Moreover, many of the unhealthy lifestyle factors included in the present study have been considered to be associated with overweight/obesity [23,24,26,28]. Therefore, to eliminate the effects of BMI status on LBP, we analyzed the association of LBP with lifestyle risk according to BMI strata (underweight, normal, and overweight/obesity). This stratified analysis showed that moderate and high lifestyle risk scores were significantly associated with LBP among all individuals except for underweight men. Moreover, regardless of BMI status, the accumulation of unhealthy lifestyle risk factors resulted in a significantly higher OR for LBP (p for trend < 0.01). These results imply that improving unhealthy lifestyle behaviors may prevent the development of LBP even in non-overweight individuals.
No simple explanation can be given with regard to the potential mechanism behind the association of A previous study has emphasized the importance of addressing the health literacy in the selfmanagement for LBP [44]. Further investigations are needed with regard to these points.
The strength of this study was the large-scale sample size that helped reduce the random error and could permit exploring the risk along multidimensional aspects of lifestyle factors. However, the present study also has several limitations. First, the determination of LBP relied on self-reports and was not based on clinical examinations. Differentiating LBP type (e.g., acute pain or chronic pain, or localized pain or radicular pain, disease-specific) might have been helpful to explore the associations found here in more detail. Second, we cannot rule out the effects of unmeasured confounders (e.g., occupation type, contents of diet, education level, or psychological status [3]). Third, we evaluated information on lifestyle factors using a self-reported questionnaire, which is prone to social desirability bias. This could lead to misclassification of exposure; the misclassification is considered non-differential in its nature, which may have resulted in dilution of a true association. Finally, we could not determine a causal relationship due to the cross-sectional nature of the study.

Conclusions
In summary, we investigated the combined effects of multiple unhealthy lifestyle behaviors on LBP among more than 400,000 Japanese adults. Our results indicated that the accumulation of unhealthy lifestyle factors was associated with increased LBP, and this was consistent across age and BMI

Availability of data and materials
The data used in the current study are available on reasonable request and with permission of the Ethics Committee of the All Japan Labor Welfare Foundation.

Competing interests
The authors declare that they have no competing interests.

Funding
This study was supported in part by Grant-in-Aid for Young Scientists (JP18K17979) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.