Defining the progression of normal and non-progression humeral shaft fracture healing using the plasma proteome

ABSTRACT Current diagnostic tools are neither informative of, nor concurrent with the underlying biological processes of fracture healing. We examined if there would be protein markers in the plasma of non-operatively fixed, isolated, non-articular, humeral fractures that would be informative of these biological processes. Five follow-up visits over a six-month period were examined in 24 patients that healed (union) and 7 non-healers (nonunion). Using the first or last clinic visit as the reference, 118 proteins out of ∼7000 proteins that were assayed, showed differential expression at log 2 fold change ≥1.3 fold and a significance of FDR ≤ 0.5. Multiple proteins related to endochondral bone development showed significant increased plasma levels during the first 12-16 weeks. Proteins associated with acute phase response, inflammation and lipid storage showed decreased levels after their initial induction. Using a time point to time point comparison for the first three follow-up visits (up to 9 weeks after injury) between healed and nonunion patients, identified 41 proteins with differential levels at p ≤ 0.05 significance, with ten overlapping the 118 proteins that tracked normal healing. The differential group associated with the nonunion patient‘s included specific extracellular matrix and acute phase proteins that showed decreased levels relative to normal healers. These data establish the progression of endochondral bone formation and place them in context to radiological and functional outcomes in human fracture healing. The identification of differentially expressed proteins in nonunion plasma suggests the potential for the development of diagnostic markers for the early intervention of nonunion. ClinicalTrials.gov# NCT05143476 Sponsor/Funding Source DOD W81XWH-19-1-0796

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Journal
Scientific Reports
Published
2026-11-06
DOI
https://doi.org/10.1038/s41598-026-74324-7
Primary Topic
Bone fractures and treatments
Type
article
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article

Defining the progression of normal and non-progression humeral shaft fracture healing using the plasma proteome

Paul Tornetta, Luke A. Lopas, Andrea L. Howe, Walter W. Virkus et al.
1 links
Scientific Reports
Bone fractures and treatments
article

Defining the progression of normal and non-progression humeral shaft fracture healing using the plasma proteome

Paul Tornetta, Luke A. Lopas, Andrea L. Howe, Walter W. Virkus, David Wilson Skinner, David S. Weiss, Glenn D. Hanson, Avani Vaishnav, Joseph Thomas Patterson, Michael M. Hadeed, Trisha Chaffee, Avani Sudhir Vaishnav, Roman M. Natoli, Suna Chung, Paul Edward Matuszewski, Yohan Jang, Robert V. O’Toole, Rudy Castillo, David B. Weiss, Nazanin Nafisi, Suna Chung, Louis C. Gerstenfeld, Kameron M. Kraus, Serkalem Demisse, Robert Azario, Serkalem Demissie (28826), Olutayo M. Alese, Tina Daoud, Robert O’Toole, METRC Corporate Authorship Members, Joshua L. Gary, George Hanson, METRC Writing Group Members, Eric D. McVey, Todd McKinley, W. Andrew Eglseder, Renan Castillo, Jason Lowe
article en

Abstract

ABSTRACT Current diagnostic tools are neither informative of, nor concurrent with the underlying biological processes of fracture healing. We examined if there would be protein markers in the plasma of non-operatively fixed, isolated, non-articular, humeral fractures that would be informative of these biological processes. Five follow-up visits over a six-month period were examined in 24 patients that healed (union) and 7 non-healers (nonunion). Using the first or last clinic visit as the reference, 118 proteins out of ∼7000 proteins that were assayed, showed differential expression at log 2 fold change ≥1.3 fold and a significance of FDR ≤ 0.5. Multiple proteins related to endochondral bone development showed significant increased plasma levels during the first 12-16 weeks. Proteins associated with acute phase response, inflammation and lipid storage showed decreased levels after their initial induction. Using a time point to time point comparison for the first three follow-up visits (up to 9 weeks after injury) between healed and nonunion patients, identified 41 proteins with differential levels at p ≤ 0.05 significance, with ten overlapping the 118 proteins that tracked normal healing. The differential group associated with the nonunion patient‘s included specific extracellular matrix and acute phase proteins that showed decreased levels relative to normal healers. These data establish the progression of endochondral bone formation and place them in context to radiological and functional outcomes in human fracture healing. The identification of differentially expressed proteins in nonunion plasma suggests the potential for the development of diagnostic markers for the early intervention of nonunion. ClinicalTrials.gov# NCT05143476 Sponsor/Funding Source DOD W81XWH-19-1-0796

Scientific Reports
Boston University (US), University of Southern California (US), University of Maryland, Baltimore (US), Boston Medical Center (US), University of Maryland Medical Center (US), Beth Israel Deaconess Medical Center (US), Harvard University (US), University of Arizona (US), University of Kentucky (US), Johns Hopkins University (US), University of Virginia Health System (US), Methodist Hospital (US), Indiana University Indianapolis (US), University of Virginia (US)
U.S. Department of Defense, University of Southern California, Indiana University Health
Good health and well-being
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Bone fractures and treatments
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