Title:Non-Targeted Metabolomics Signature in the Plasma and Bone Marrow of Patients with Long Bone Injuries
VOLUME: 7 ISSUE: 1
Author(s):Hend Ibrahim, Omar Alnachoukati, Bridget A. Baxter, Trinette Chapin, Thomas Schroeppel, Julie Dunn and Elizabeth P. Ryan*
Affiliation:Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, University of Colorado Health System, Medical Center of the Rockies, Department of Surgery - Trauma and Acute Care, Fort Collins, CO 80523, Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523, University of Colorado Health System, Medical Center of the Rockies, Department of Surgery - Trauma and Acute Care, Fort Collins, CO 80523, University of Colorado Health, Memorial Hospital, Department of Acute Care Surgery, Colorado Springs, CO 80909, University of Colorado Health System, Medical Center of the Rockies, Department of Surgery - Trauma and Acute Care, Fort Collins, CO 80523, Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO 80523
Keywords:Bone marrow, plasma, metabolomics, fracture, reaming, trauma, inflammation.
Abstract:
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.