Causal effect between systemic inflammatory cytokines and osteoporotic pathological fractures: A bidirectional...

Area of Science:

• Genetics
• Immunology
• Metabolic Bone Disease

Background:

• Osteoporosis is a common metabolic bone disease impacting quality of life.
• The relationship between systemic inflammation and bone metabolism is increasingly recognized but not fully understood.
• Causal links between inflammatory factors and osteoporotic fractures require elucidation.

Purpose of the Study:

• To investigate potential causal relationships between circulating inflammatory factors and osteoporotic pathological fractures.
• To explore the bidirectional nature of the association between inflammation and osteoporosis.

Main Methods:

• A bidirectional 2-sample Mendelian randomization (MR) approach was utilized.
• Large-scale genetic data from the FinnGen biobank and GWAS catalog were analyzed for 91 inflammatory factors.
• Inverse variance weighted (IVW) method was the primary analysis, supported by MR-Egger, weighted median, and mode-based estimators, with sensitivity analyses performed.

Main Results:

• Forward MR identified 7 inflammatory factors causally associated with osteoporotic fracture risk.
• Elevated Artemin levels were linked to decreased fracture risk (OR=0.7954, P=.0167).
• Increased levels of β-nerve growth factor, CXCL10, CXCL6, IL-10 receptor α/β subunits, and LTBP1 were associated with higher fracture risk.
• Reverse MR indicated fractures may decrease levels of CXCL11, IL-1α, TSLP, and increase TNF-β levels.

Conclusions:

• A complex, bidirectional interplay exists between circulating inflammatory factors and osteoporotic pathological fractures.
• Findings offer new insights into osteoporosis pathogenesis.
• Results suggest potential avenues for novel preventive, diagnostic, and therapeutic strategies for osteoporosis.