Causal association between inflammatory cytokines and osteonecrosis: A bidirectional 2-sample Mendelian randomization...

Area of Science:

• Immunology
• Genetics
• Orthopedics

Background:

• Immune-inflammatory responses are implicated in osteonecrosis (ON) pathogenesis.
• Specific inflammatory regulators driving ON remain largely unidentified.

Purpose of the Study:

• To investigate causal associations between circulating inflammatory proteins and osteonecrosis using a bidirectional Mendelian randomization (MR) approach.
• To identify potential therapeutic targets for osteonecrosis by examining the role of inflammatory mediators.

Main Methods:

• Utilized a bidirectional Mendelian randomization (MR) study design.
• Employed genetic instrumental variables for 91 circulating inflammatory proteins from a large genome-wide association study (GWAS).
• Analyzed osteonecrosis summary statistics from the FinnGen database, applying inverse-variance weighted (IVW) method and sensitivity analyses.

Main Results:

• CDCP1 was causally associated with an increased risk of osteonecrosis (OR = 1.23).
• Increased concentrations of CSF1 (OR = 0.72), IL-10RB (OR = 0.84), and MCP-4 (OR = 0.81) were associated with a reduced risk of osteonecrosis.
• Reverse MR analysis suggested IL-18 may act as a protective factor against osteonecrosis (OR = 0.97).

Conclusions:

• Identified specific inflammatory proteins, including CDCP1, CSF1, IL-10RB, MCP-4, and IL-18, with potential causal roles in osteonecrosis pathophysiology.
• These findings highlight novel therapeutic avenues for managing osteonecrosis.
• The study provides genetic evidence for the link between inflammation and osteonecrosis.