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

Increasing evidence suggests that immune-inflammatory responses are closely associated with osteonecrosis (ON). However, the specific inflammatory regulators involved in this pathogenesis remain unclear. Using a bidirectional Mendelian randomization (MR) investigation, we methodically investigated circulating inflammatory proteins that are causally linked to osteonecrosis. The genetic tools for 91 inflammatory circulating proteins were from a genome-wide association study with 14,824 participants, most of whom were from Europe. The ON summary statistics were acquired from the FinnGen database. The main strategy for drawing conclusions about causality was the inverse-variance weighted (IVW) method. The final results were supported by a number of sensitivity studies, including MR-Egger, weighted median, simple mode, weighted mode, and linkage disequilibrium score regression (LDSC). A link between CDCP1 and a higher risk of osteonecrosis has been revealed by genetic data (IVW OR = 1.23, 95% CI = 1.01-1.50, P = .037). Increased concentrations of CSF1 (IVW OR = 0.72, 95% CI = 0.54-0.96, P = .026), IL-10RB (IVW OR = 0.84, 95% CI = 0.699-0.999, P = .049), and MCP-4 (IVW OR = 0.81, 95% CI = 0.67-0.99, P = .038) were associated with a reduced risk of ON, while ON did not significantly affect these proteins. Only IL-18 may be a protective factor against osteonecrosis, according to reverse MR data (IVW OR = 0.97, 95% CI = 0.94-0.999, P = .042). This MR study investigated the causal associations between 91 inflammatory cytokines and osteonecrosis in detail overall. We discovered causal connections between reverse magnetic resonance imaging (reverse MR) and CDCP1, CSF1, MCP-4, and IL-18. These elements might contribute significantly to the pathophysiology of ON and might present fresh treatment options for the illness.