Systemic Inflammatory Regulators Associated with Osteoporosis: A Bidirectional Mendelian Randomization Study

Area of Science:

• Genetics and Molecular Biology
• Immunology
• Bone Biology

Background:

• Osteoporosis (OP) progression is influenced by inflammatory factors.
• Understanding the precise regulatory mechanisms and causal relationships is crucial.

Purpose of the Study:

• To elucidate upstream and downstream regulatory mechanisms of inflammatory factors in OP.
• To establish a causal relationship between inflammatory factors and OP using bidirectional Mendelian randomization.

Main Methods:

• Bidirectional Mendelian randomization (MR) analyses were performed.
• Data from Finnish cohorts (cytokines) and UK Biobank (eBMD, fractures) were utilized.
• Inverse variance-weighted method, MR-Egger regression, and heterogeneity tests were applied.

Main Results:

• Macrophage inflammatory protein (MIP)-1α and interleukin (IL)-12p70 causally associated with decreased estimated bone mineral density (eBMD).
• Tumor necrosis factor-related apoptosis-inducing ligand showed a decreased risk of fractures.
• OP influenced multiple inflammatory factors, and bidirectional causal relationships were found between IL-8, IL-10, and OP.

Conclusions:

• Specific inflammatory factors have bidirectional causal relationships with OP.
• Findings offer new perspectives for early prediction and targeted treatment of osteoporosis.
• Further validation in larger cohorts is recommended.