Intervertebral Disk Degeneration and Bone Mineral Density: A Bidirectional Mendelian Randomization Study

This study aimed to investigate the causal relationship between bone mineral density (BMD) and intervertebral disk degeneration (IVDD) using a two-sample bidirectional Mendelian randomization analysis.

Summary-level data from the Genome-Wide Association Study (GWAS) were used.

Instrumental variables (IVs) for IVDD were selected from the large-scale Genome-Wide Association Study (GWAS) (20,001 cases and 164,682 controls).

Bone mineral density (BMD) at five different sites (heel ( n  = 426,824), total body (TB) ( n  = 56,284), forearm (FA) ( n  = 8143), femoral neck (FN) ( n  = 32,735), and lumbar spine (LS) ( n  = 28,498)) was used as a phenotype for OP.

Bidirectional causality between IVDD and BMD was assessed using inverse variance weighting (IVW) and other methods.

Related sensitivity analyses were performed.

Myopia was also analyzed as a negative control result to ensure the validity of IVs.

Heel bone mineral density (heel BMD), total body bone mineral density (TB-BMD), femoral neck bone mineral density (FN-BMD), and lumbar spine bone mineral density (LS-BMD) have a direct causal relationship on intervertebral disk degeneration (IVDD) [heel BMD-related analysis: beta = 0.06, p  = 0.03; TB-BMD-related analysis: beta = 0.18, p  = 8.72E-08; FN-BMD-related analysis: beta = 0.15, p  = 4.89E-03; LS-BMD-related analysis: beta = 0.16, p  = 1.43E-04].

There was no evidence of a significant causal effect of IVDD on BMD.

In conclusion, our study found a significant positive causal effect of lower BMD on IVDD, and we identified significant causal effects of heel, TB-, FN-, and LS-BMD on IVDD, but there was no evidence of a significant causal effect of IVDD on BMD.