Metabolic Syndrome and Low Back Pain: Evidence from Cross-Sectional and Mendelian Randomization Analysis

Xingkun Wang,1,2 Dingnan Sun,3 Heng Duan,1,2 Yuxuan Yang,1,2 Hua Zhao1 1Department of Orthopedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 3Clinical Medical College of Jining Medical University, Jining Medical University, Jining, People’s Republic of ChinaCorrespondence: Hua Zhao, Department of Orthopedics, Qilu Hospital of Shandong University, Cheeloo College of Medicine, Shandong University, No. 107, Wenhuaxi Road, Lixia District, Jinan, Shandong, 250012, People’s Republic of China, Tel +8618560088189, Email zhaohuadr@163.comBackground: Metabolic syndrome (MetS) and low back pain (LBP) are major health concerns, but their relationship remains unclear. Components of MetS, such as abdominal obesity and hypertension, may contribute to musculoskeletal degeneration. This study investigated the association and causality between MetS and LBP.Methods: We analyzed 5,523 adults (≥ 20 years) from NHANES 1999– 2004 with complete MetS and LBP data. MetS was defined using National Cholesterol Education Program’s Adult Treatment Panel III (ATPIII), International Diabetes Federation (IDF), and “modified World Health Organization (mWHO) criteria”. Weighted logistic regression and stratified analyses assessed associations. Mediation analysis examined the role of C-reactive protein (CRP), and Mendelian randomization (MR) using GWAS summary statistics tested causal effects of MetS components on LBP.Results: MetS prevalence was higher in participants with LBP (IDF: 41.0% vs 34.4%; ATPIII: 31.6% vs 25.8%; mWHO: 25.6% vs 21.2%). Fully adjusted models confirmed significant associations: IDF (OR = 1.27; 95% CI: 1.06– 1.53), ATPIII (OR = 1.26; 95% CI: 1.05– 1.50), mWHO (OR = 1.21; 95% CI: 1.03– 1.42). CRP did not mediate these associations. MR analysis supported causal effects of hypertension (OR = 2.34; 95% CI: 1.38– 3.97; FDR p = 0.002) and waist circumference (OR = 1.45; 95% CI: 1.34– 1.57; FDR p < 0.001) on LBP, while other MetS components showed no causal links.Conclusion: MetS is associated with LBP across multiple definitions, with genetic evidence implicating abdominal obesity and hypertension. Improving metabolic health may be a promising strategy to reduce LBP burden.Keywords: metabolic syndrome, low back pain, mendelian randomization, NHANES, epidemiology