Non-Targeted Metabolomics Signature in the Plasma and Bone Marrow of Patients with Long Bone Injuries

Background:The contribution of long bone injury and reaming to the inflammatory response of trauma is unknown.Introduction:This study evaluated whether metabolomics can be used to (1) reveal differences in the plasma from long bone injury trauma patients before and after reaming and (2) distinguish healthy adult plasma from that of trauma patients.Methods:Prospective cohort study with enrollment from February 17, 2017 to December 5, 2017 included 15 patients with long bone injuries and 20 healthy adults. Patients with femoral or tibial fractures scheduled to undergo intramedullary nailing were identified at the Medical Center of the Rockies, (Loveland, Co), and Memorial Hospital, (Colorado Springs, CO). Pre-and post-reaming plasma and bone marrow from fifteen patients with femoral and tibial fractures and 20 heathy adult plasma were analyzed by ultra-high-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS).Results:Trauma patients had 1259 plasma metabolites and healthy adults had 1272 plasma metabolites detected. Fifty percent (657 metabolites) were common between the bone marrow and plasma profiles, and 304 metabolites showed statistical significance for differential abundance between pre- and post-reaming (P<0.05). Post-ream lipids, fatty acids and ceramides were 1.09-1.46-fold increased and diacylglycerols were 0.73-0.82-fold decreased compared to the pre-ream patient control. Post-ream tryptophan metabolites were decreased 0.84-fold, whereas cysteine metabolites were elevated 1.42-fold. Metabolite signals associated with bone matrix remodeling, stress and inflammation were modulated in all patients.Conclusion:Plasma metabolite signatures changed in long bone fracture patients pre- and post-reaming showing distinct profiles from healthy adults without trauma injury. Metabolite signatures of long bone trauma patients have an inflammatory response reflective of healing cascades and merits additional testing for markers of individualized responses to injury.