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

Kun Zhu1,2, ZiJie An2, YaWei Li3

  • 1Department of Orthopaedics, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Scientific Reports
|March 26, 2025
PubMed
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Low bone mineral density (BMD) causally increases the risk of postural instability. This genetic link suggests osteoporosis patients face higher risks of balance issues.

Keywords:
Bone mineral densityCausalityMendelian randomization studyOsteoporosisPostural instability

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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.