Causal relationship between intervertebral disc degeneration and osteoporosis: a bidirectional two-sample Mendelian randomization study

Introduction The relationship between intervertebral disc degeneration (IVDD) and osteoporosis (OP), diagnosed primarily using bone mineral density (BMD), remains unclear so far. The present study, therefore, aimed to investigate the potential relationship between osteoporosis and intervertebral disc degeneration using Mendelian randomization and genome-wide association analyses. Specifically, the impact of bone mineral density on the development of intervertebral disc degeneration was evaluated. Materials and methods The genome-wide association studies (GWAS) summary data of OP/BMDs and IVDD were collected from the FinnGen consortium, the GEFOS consortium, and MRC-IEU. The relationship between IVDD and OP was then explored using TSMR. The inverse-variance weighted (IVW) method was adopted as the primary effect estimate, and the reliability and stability of the results were validated using various methods, including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO. Results No significant causal relationship was observed between OP and IVDD (IVW, P > 0.05) or between femoral neck BMD (FA-BMD) and IVDD when OP and FA-BMD were used as exposures. However, increased levels of total body BMD (TB-BMD) and lumbar spine BMD (LS-BMD) were revealed as significant risk factors for IVDD (TB-BMD: IVW, OR = 1.201, 95% CI: 1.123-1.284, P = 8.72 x 10(-8); LS-BMD: IVW, OR = 1.179, 95% CI: 1.083-1.284, P = 1.43 x 10-4). Interestingly, both heel BMD (eBMD) and femur neck BMD (FN-BMD) exhibited potential causal relationships (eBMD: IVW, OR = 1.068, 95% CI: 1.008-1.131, P = 0.0248; FN-BMD, IVW, OR = 1.161, 95% CI: 1.041-1.295, P = 0.0074) with the risk of IVDD. The reverse MR analysis revealed no statistically causal impact of IVDD on OP and the level of BMD (P > 0.05). Conclusion OP and the level of FA-BMD were revealed to have no causal relationship with IVDD. The increased levels of TB-BMD and LS-BMD could promote the occurrence of IVDD. Both eBMD and FN-BMD have potential causal relationships with the risk of IVDD. No significant relationship exists between IVDD and the risk of OP. Further research is warranted to comprehensively comprehend the molecular mechanisms underlying the impact of OP and BMD on IVDD and vice versa.