Primary biliary cirrhosis and osteoporosis: a bidirectional two-sample Mendelian randomization study

Area of Science:

• Hepatology
• Endocrinology
• Genetics

Background:

• Observational studies suggest a link between primary biliary cholangitis (PBC) and increased risk of osteoporosis and fractures.
• A definitive causal relationship and underlying mechanisms remain unclear.

Purpose of the Study:

• To investigate the causal relationship between primary biliary cholangitis (PBC) and osteoporosis using a bidirectional two-sample Mendelian randomization (MR) analysis.
• To determine if PBC causes osteoporosis or vice versa.

Main Methods:

• Utilized five MR methods (IVW, MR-Egger, weighted median, weighted mode, simple mode) for robust analysis.
• Performed sensitivity analyses to assess heterogeneity and pleiotropy, ensuring reliability of instrumental variables (IVs).

Main Results:

• Established a causal link between PBC and increased osteoporosis risk (OR: 1.049, P=0.002) via IVW analysis, supported by other MR methods.
• Found no evidence of a causal effect of osteoporosis on PBC risk (OR: 0.941, P=0.511).
• Confirmed no significant heterogeneity or horizontal pleiotropy among IVs, with leave-one-out analysis showing robust findings.

Conclusions:

• This study confirms a causal relationship where primary biliary cholangitis (PBC) increases the risk of developing osteoporosis.
• No causal link was identified from osteoporosis to PBC, providing clarity on the directionality of the relationship.
• Findings offer crucial insights for optimizing bone health management strategies in patients diagnosed with PBC.