Association between BMD and coronary artery calcification: an observational and Mendelian randomization study

Area of Science:

• Biomedical Research
• Epidemiology
• Genetics

Background:

• Observational studies show inconsistent links between bone mineral density (BMD) and coronary artery calcification (CAC).
• Understanding the relationship is crucial for identifying shared risk factors for osteoporosis and cardiovascular disease.

Purpose of the Study:

• To investigate the observational association between BMD and CAC.
• To evaluate potential causal relationships between BMD and CAC using Mendelian randomization (MR) and polygenic risk scores (PRS).

Main Methods:

• Utilized data from two large population-based cohorts: the Rotterdam Study (1414 participants) and the Framingham Heart Study (2233 participants).
• Employed linear regression for observational analysis and 1- and 2-sample Mendelian randomization (MR) with inverse variance weighted (IVW) and 2-stage least squares regression for causal inference.
• Assessed BMD at total body, lumbar spine, and femoral neck, alongside CAC measurements.

Main Results:

• No robust observational associations were found between BMD levels and CAC across different skeletal sites.
• Mean CAC showed a uniform random distribution across polygenic risk score for BMD (PRSBMD) quintile groups.
• Neither 1-sample nor 2-sample MR analyses supported a causal association between BMD and CAC.

Conclusions:

• The study does not support a causal relationship where lower BMD increases the risk of CAC.
• Reported epidemiological associations between BMD and CAC are likely attributable to unmeasured confounders or shared underlying etiologies.
• Findings suggest osteoporosis and vascular calcification may not share direct causal pathways.