Osteoporosis and Primary Biliary Cholangitis: A Trans-ethnic Mendelian Randomization Analysis

Area of Science:

• Hepatology
• Endocrinology
• Rheumatology

Background:

• Osteoporosis is a significant complication in autoimmune diseases like primary biliary cholangitis (PBC).
• Fractures and associated mortality are major consequences of osteoporosis.
• The causal link between PBC and osteoporosis requires elucidation.

Purpose of the Study:

• To investigate the causal relationship between primary biliary cholangitis (PBC) and osteoporosis.
• To determine if this causal link is independent of potential confounding factors.

Main Methods:

• Bidirectional Mendelian randomization (MR) analyses were conducted in European and East Asian cohorts.
• Multivariable MR analyses assessed the direct effect of PBC on osteoporosis.
• Trans-ethnic meta-analysis pooled estimates from different ethnic groups.

Main Results:

• Genetic liability to PBC was significantly associated with an increased risk of osteoporosis in Europeans (OR, 1.040; P=0.001).
• This causal effect persisted after adjusting for BMI, calcium, lipidemic traits, and sex hormones.
• Replication in East Asians and trans-ethnic meta-analysis confirmed the association (P=0.001 and P=8.17×10⁻⁶, respectively).

Conclusions:

• Primary biliary cholangitis (PBC) causally increases the risk of developing osteoporosis.
• The observed causality is independent of key metabolic and hormonal factors.
• These findings highlight a crucial link between autoimmune liver disease and bone health.