A causal association between osteoporosis and postural instability: a Mendelian randomization study.

Area of Science:

• Bone biology and aging
• Biostatistics and epidemiology
• Genetics and public health

Background:

• Observational studies suggest osteoporosis and postural instability are linked.
• A definitive genetic causal relationship between osteoporosis and postural instability remains unclear.

Purpose of the Study:

• To investigate the potential causal relationship between osteoporosis, using bone mineral density (BMD) as a proxy, and postural instability.
• To leverage a two-sample Mendelian randomization analysis for robust causal inference.

Main Methods:

• Two-sample Mendelian randomization (MR) analysis utilizing Inverse Variance Weighted (IVW), weighted median, and MR-Egger methods.
• Steiger filtering, FDR correction, Cochran Q statistic, MR-PRESSO, MR-Egger intercept, and leave-one-out analyses were employed for rigorous assessment and sensitivity analysis.
• Genetic variants associated with BMD (femoral neck, lumbar spine, and forearm) were used as instrumental variables.

Main Results:

• A significant negative causal correlation was found between femoral neck BMD (FN-BMD) and postural instability (OR=0.9171, FDR P=0.0009).
• Lumbar spine BMD (LS-BMD) also showed a significant negative causal association with postural instability (OR=0.9491, FDR P=0.0129).
• No significant causal link was observed between forearm BMD (FA-BMD) and postural instability; sensitivity analyses confirmed no significant heterogeneity or pleiotropy for FN-BMD and LS-BMD.

Conclusions:

• This study provides genetic evidence for a causal association between reduced BMD and increased postural instability.
• Individuals with osteoporosis, characterized by lower BMD, may have an elevated risk of experiencing postural instability.
• Targeting BMD could be a potential strategy for mitigating postural instability risks.