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

Area of Science:

• Genetics
• Orthopedics
• Epidemiology

Background:

• The link between osteoporosis (OP) and intervertebral disc degeneration (IVDD) is not fully understood, despite OP being diagnosed by bone mineral density (BMD).
• Investigating the genetic relationship between OP and IVDD is crucial for understanding spinal health.

Purpose of the Study:

• To investigate the potential causal relationship between osteoporosis and intervertebral disc degeneration using Mendelian randomization and genome-wide association analyses.
• To evaluate the impact of different bone mineral density measurements on the development of intervertebral disc degeneration.

Main Methods:

• Genome-wide association studies (GWAS) summary data for OP/BMD and IVDD were obtained from large consortiums.
• Two-sample Mendelian randomization (TSMR) analysis was employed, using inverse-variance weighted (IVW) as the primary method, with MR-Egger, weighted median, and MR-PRESSO for validation.

Main Results:

• No significant causal link was found between OP and IVDD, or between femoral neck BMD (FA-BMD) and IVDD.
• Increased total body BMD (TB-BMD) and lumbar spine BMD (LS-BMD) were identified as significant risk factors for IVDD.
• Heel BMD (eBMD) and femur neck BMD (FN-BMD) showed potential causal relationships with IVDD risk. Reverse MR analysis indicated no causal effect of IVDD on OP or BMD levels.

Conclusions:

• Osteoporosis and FA-BMD do not appear to causally influence IVDD.
• Elevated TB-BMD and LS-BMD are associated with an increased risk of developing IVDD.
• eBMD and FN-BMD may have a causal role in IVDD. Further research is needed to elucidate the underlying molecular mechanisms.