A pilot study of circulating levels of TGF-β1 and TGF-β2 as biomarkers of bone healing in patients with non-hypertrophic pseudoarthrosis of long bones

Background: Pseudoarthrosis or non-union is a complication with an incidence of 5–10% of bone fractures, most frequently located in the diaphysis of long bones. The management of this complication is addressed by means of complex surgical procedures and is a concern for orthopaedic and trauma surgeo...

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Main Authors: Daniel Chaverri, Daniel Vivas, Santiago Gallardo-Villares, Fernando Granell-Escobar, Javier A. Pinto, Joaquim Vives
Format: Article
Language:English
Published: Elsevier 2022-06-01
Series:Bone Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2352187221004149
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author Daniel Chaverri
Daniel Vivas
Santiago Gallardo-Villares
Fernando Granell-Escobar
Javier A. Pinto
Joaquim Vives
author_facet Daniel Chaverri
Daniel Vivas
Santiago Gallardo-Villares
Fernando Granell-Escobar
Javier A. Pinto
Joaquim Vives
author_sort Daniel Chaverri
collection DOAJ
description Background: Pseudoarthrosis or non-union is a complication with an incidence of 5–10% of bone fractures, most frequently located in the diaphysis of long bones. The management of this complication is addressed by means of complex surgical procedures and is a concern for orthopaedic and trauma surgeons nowadays. The use of biomarkers for diagnosing patients at risk of non-union would help us to establish special measures for early corrective treatment. Methods: Prospective exploratory pilot study with a cohort of 20 patients diagnosed of non-hypertrophic pseudoarthrosis of long bones who were treated surgically with either autologous bone graft or a Tissue Engineering Product composed of bone marrow-derived Mesenchymal Stromal Cells. Patients were followed for 12 months and plasma blood samples were obtained to determine circulating levels of Transforming Growth Factor Beta 1 and Beta 2 (TGF-β1 and TGF-β2, respectively) at inclusion, and at 1 week, 2 weeks, and months 1, 2, 3, 6 and 12 after surgery. Radiological bone healing was evaluated by the Tomographic Union Score (TUS). Results: Basal levels of TGF-β1 and TGF-β2 were determined in the twenty patients (26,702 ± 14,537 pg/mL and 307.8 ± 83.1 pg/mL, respectively). Three of them withdrew from the study, so complete follow-up was conducted on 17 patients (9 successfully healed vs. 8 that did not heal). Statistically significant differences between the bone healing group and the non-union group were found at month 12 for both TGF-β1 (p = 0.005) and TGF-β2 (p = 0.02). Conclusions: TGF-β1 and TGF-β2 are biomarkers that correlate with clinical evidence of bone regeneration and may be used to monitor patients, although early predictive value after intervention needs to be further studied in combination with other molecules.
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spelling doaj.art-2a262705e6dd41d38d78a4af892b7b732022-12-22T02:29:51ZengElsevierBone Reports2352-18722022-06-0116101157A pilot study of circulating levels of TGF-β1 and TGF-β2 as biomarkers of bone healing in patients with non-hypertrophic pseudoarthrosis of long bonesDaniel Chaverri0Daniel Vivas1Santiago Gallardo-Villares2Fernando Granell-Escobar3Javier A. Pinto4Joaquim Vives5Orthopaedic Surgery and Traumatology Department, ASEPEYO Sant Cugat Hospital, Avinguda Alcalde Barnils, 54-60, Sant Cugat del Vallès, 08174 Barcelona, Spain; Corresponding author.Servei de Teràpia Cel·lular, Banc de Sang i Teixits, Edifici Dr. Frederic Duran i Jordà, Passeig Taulat, 116, 08005 Barcelona, SpainOrthopaedic Surgery and Traumatology Department, ASEPEYO Sant Cugat Hospital, Avinguda Alcalde Barnils, 54-60, Sant Cugat del Vallès, 08174 Barcelona, SpainOrthopaedic Surgery and Traumatology Department, ASEPEYO Sant Cugat Hospital, Avinguda Alcalde Barnils, 54-60, Sant Cugat del Vallès, 08174 Barcelona, SpainRadiodiagnostic Department, ASEPEYO Sant Cugat Hospital, Avinguda Alcalde Barnils, 54-60, Sant Cugat del Vallès, 08174 Barcelona, SpainServei de Teràpia Cel·lular, Banc de Sang i Teixits, Edifici Dr. Frederic Duran i Jordà, Passeig Taulat, 116, 08005 Barcelona, Spain; Musculoskeletal Tissue Engineering Group, Vall d'Hebron Research Institute (VHIR), Universitat Autònoma de Barcelona, Passeig de la Vall d'Hebron 129-139, 08035 Barcelona, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Passeig de la Vall d'Hebron 129-139, 08035 Barcelona, Spain; Correspondence to: J. Vives, Servei de Teràpia Cellular, Banc de Sang i Teixits, Edifici Dr. Frederic Duran i Jordà, Passeig Taulat, 116, 08005 Barcelona, Spain.Background: Pseudoarthrosis or non-union is a complication with an incidence of 5–10% of bone fractures, most frequently located in the diaphysis of long bones. The management of this complication is addressed by means of complex surgical procedures and is a concern for orthopaedic and trauma surgeons nowadays. The use of biomarkers for diagnosing patients at risk of non-union would help us to establish special measures for early corrective treatment. Methods: Prospective exploratory pilot study with a cohort of 20 patients diagnosed of non-hypertrophic pseudoarthrosis of long bones who were treated surgically with either autologous bone graft or a Tissue Engineering Product composed of bone marrow-derived Mesenchymal Stromal Cells. Patients were followed for 12 months and plasma blood samples were obtained to determine circulating levels of Transforming Growth Factor Beta 1 and Beta 2 (TGF-β1 and TGF-β2, respectively) at inclusion, and at 1 week, 2 weeks, and months 1, 2, 3, 6 and 12 after surgery. Radiological bone healing was evaluated by the Tomographic Union Score (TUS). Results: Basal levels of TGF-β1 and TGF-β2 were determined in the twenty patients (26,702 ± 14,537 pg/mL and 307.8 ± 83.1 pg/mL, respectively). Three of them withdrew from the study, so complete follow-up was conducted on 17 patients (9 successfully healed vs. 8 that did not heal). Statistically significant differences between the bone healing group and the non-union group were found at month 12 for both TGF-β1 (p = 0.005) and TGF-β2 (p = 0.02). Conclusions: TGF-β1 and TGF-β2 are biomarkers that correlate with clinical evidence of bone regeneration and may be used to monitor patients, although early predictive value after intervention needs to be further studied in combination with other molecules.http://www.sciencedirect.com/science/article/pii/S2352187221004149BiomarkerBlood sampleBone regenerationPseudoarthrosisNon-unionMultipotent Mesenchymal Stromal Cells
spellingShingle Daniel Chaverri
Daniel Vivas
Santiago Gallardo-Villares
Fernando Granell-Escobar
Javier A. Pinto
Joaquim Vives
A pilot study of circulating levels of TGF-β1 and TGF-β2 as biomarkers of bone healing in patients with non-hypertrophic pseudoarthrosis of long bones
Bone Reports
Biomarker
Blood sample
Bone regeneration
Pseudoarthrosis
Non-union
Multipotent Mesenchymal Stromal Cells
title A pilot study of circulating levels of TGF-β1 and TGF-β2 as biomarkers of bone healing in patients with non-hypertrophic pseudoarthrosis of long bones
title_full A pilot study of circulating levels of TGF-β1 and TGF-β2 as biomarkers of bone healing in patients with non-hypertrophic pseudoarthrosis of long bones
title_fullStr A pilot study of circulating levels of TGF-β1 and TGF-β2 as biomarkers of bone healing in patients with non-hypertrophic pseudoarthrosis of long bones
title_full_unstemmed A pilot study of circulating levels of TGF-β1 and TGF-β2 as biomarkers of bone healing in patients with non-hypertrophic pseudoarthrosis of long bones
title_short A pilot study of circulating levels of TGF-β1 and TGF-β2 as biomarkers of bone healing in patients with non-hypertrophic pseudoarthrosis of long bones
title_sort pilot study of circulating levels of tgf β1 and tgf β2 as biomarkers of bone healing in patients with non hypertrophic pseudoarthrosis of long bones
topic Biomarker
Blood sample
Bone regeneration
Pseudoarthrosis
Non-union
Multipotent Mesenchymal Stromal Cells
url http://www.sciencedirect.com/science/article/pii/S2352187221004149
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