Systemic Lipid Metabolism Dysregulation as a Possible Driving Force of Fracture Non-Unions?

Non-unions are fractures that do not heal properly, resulting in a false joint formation at the fracture site. This condition leads to major health issues and imposes a burden on national healthcare systems. The etiology of non-unions is still not fully understood; therefore, we aimed to identify potential systemic factors that may contribute to their formation. We conducted a cross-sectional concomitant proteomic and metabolomic pilot study of blood plasma in patients with non-unions (N = 11) and compared them with patients with bone fracture in the normal active healing phase (N = 12). We found five significantly upregulated proteins in the non-union group: immunoglobulin heavy variable 3-74, immunoglobulin lambda variable 2-18, low-density lipoprotein receptor-related protein 4, zinc-alpha-2-glycoprotein, and serum amyloid A-1 protein; and we found one downregulated protein: cystatin-C. The metabolomic study found differences in alanine, aspartate and glutamate metabolism pathways between two groups. The combined results of proteomic and metabolomic analyses suggest that the dysregulation of lipid metabolism may contribute to non-union formation.