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

Daniel Chaverri; Daniel Vivas; Santiago Gallardo-Villares; Fernando Granell-Escobar; Javier A Pinto; Joaquim Vives

doi:10.1016/j.bonr.2021.101157

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 Rep. 2021 Dec 9:16:101157. doi: 10.1016/j.bonr.2021.101157. eCollection 2022 Jun.

Authors

Daniel Chaverri¹, Daniel Vivas², Santiago Gallardo-Villares¹, Fernando Granell-Escobar¹, Javier A Pinto³, Joaquim Vives^{2

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Affiliations

¹ Orthopaedic Surgery and Traumatology Department, ASEPEYO Sant Cugat Hospital, Avinguda Alcalde Barnils, 54-60, Sant Cugat del Vallès, 08174 Barcelona, Spain.
² Servei de Teràpia Cel·lular, Banc de Sang i Teixits, Edifici Dr. Frederic Duran i Jordà, Passeig Taulat, 116, 08005 Barcelona, Spain.
³ Radiodiagnostic Department, ASEPEYO Sant Cugat Hospital, Avinguda Alcalde Barnils, 54-60, Sant Cugat del Vallès, 08174 Barcelona, Spain.
⁴ 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.
⁵ Department of Medicine, Universitat Autònoma de Barcelona, Passeig de la Vall d'Hebron 129-139, 08035 Barcelona, Spain.

Abstract

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.

Keywords: Biomarker; Blood sample; Bone regeneration; Clinical trial; Humans; Multipotent Mesenchymal Stromal Cells; Non-union; Pseudoarthrosis; Transforming Growth Factor-Beta 1; Transforming Growth Factor-Beta 2.