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Causal links between multi-domain risk factors and intervertebral disc degeneration: a systematic review and

Hang Zhang1, Jingnan Tian1, Yuchi Lu1

  • 1Department of Orthopedics, Affiliated Hospital of Changchun University of Chinese Medicine, No. 1478, Gongnong Avenue, Chaoyang District, Changchun City, Jilin Province, China.

BMC Musculoskeletal Disorders
|June 4, 2026
PubMed
Abstract

Insights

This study found that higher bone mineral density and certain lifestyle factors like watching TV increase the risk of intervertebral disc degeneration (IVDD). Conversely, some inflammatory cytokines and gut bacteria may be protective against IVDD.

Area of Science:

  • Genetics and Epidemiology
  • Musculoskeletal Health
  • Microbiome Research

Background:

  • The causal factors contributing to intervertebral disc degeneration (IVDD) are not fully understood.
  • Mendelian randomization (MR) offers advantages over observational studies for identifying causal relationships.
  • Existing MR studies for IVDD exhibit heterogeneity, leading to uncertainty in causal estimates for factors like bone health, metabolism, inflammation, gut microbiota, and lifestyle.

Purpose of the Study:

  • To synthesize Mendelian randomization (MR) evidence to investigate the causal associations between various exposure factors and intervertebral disc degeneration (IVDD).

Main Methods:

  • Conducted a systematic review and meta-analysis of MR studies on IVDD published up to September 30, 2025.
  • Assessed reporting completeness using STROBE-MR criteria.
  • Included twenty MR studies, with 12 rated as "Excellent" and 8 as "Good".

Main Results:

  • Elevated bone mineral density (BMD) across multiple sites (total body, lumbar spine, heel, femoral neck) was associated with increased IVDD risk.
  • Specific inflammatory cytokines (IFN-γ, IL-18) showed inverse associations, suggesting a protective role.
  • Certain gut bacteria (Marvinbryantia, Bacteroidetes) were linked to increased IVDD risk, while others (Rhodospirillales, Rhodospirillaceae, Ruminococcaceae UCG003) were protective.
  • Modifiable factors like prolonged TV watching, smoking initiation, greater height, larger waist circumference, higher BMI, elevated triglycerides, and Type 2 diabetes were causally associated with increased IVDD risk.

Conclusions:

  • This synthesis highlights potential causal links between multiple factors and IVDD based on current MR evidence.
  • Genetically predicted time spent watching TV emerged as a significant modifiable lifestyle factor associated with IVDD risk.
  • Findings can guide future research into the mechanisms and prevention strategies for IVDD.
Keywords:
Intervertebral disc degenerationMendelian randomizationMeta-analysisMulti-domainProtective factorsRisk factors

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