Toward the Clinical Use of Circulating Biomarkers Predictive of Bone Union

Chaverri, Daniel; Vives, Joaquim

doi:10.2217/bmm-2017-0180

Cited by 5 publications

(3 citation statements)

References 44 publications

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“…No standard diagnostic criteria for chronic nonunion has been shown to delay the requirement for treatment, which costs significantly more than those uncomplicated fracture healing [25]. Aside from radiological and clinical examination, serologic markers show promise in predicting the status and quality of fracture healing [26]. The ideal biomarker of bone healing must have the characteristics of accuracy, high sensitivity, specificity, and rapidity, and be inexpensive, and able to predict the outcome of bone nonunion [27].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic analysis and experimental identification of blood biomarkers for chronic nonunion

Liu

et al. 2020

J Orthop Surg Res

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Background Incomplete fracture healing may lead to chronic nonunion; thus, determining fracture healing is the primary issue in the clinical treatment. However, there are no validated early diagnostic biomarkers for assessing chronic nonunion. In this study, bioinformatics analysis combined with an experimental verification strategy was used to identify blood biomarkers for chronic nonunion. Methods First, differentially expressed genes in chronic nonunion were identified by microarray data analysis. Second, Dipsaci Radix (DR), a traditional Chinese medicine for fracture treatment, was used to screen the drug target genes. Third, the drug-disease network was determined, and biomarker genes were obtained. Finally, the potential blood biomarkers were verified by ELISA and qPCR methods. Results Fifty-five patients with open long bone fractures (39 healed and 16 nonunion) were enrolled in this study, and urgent surgical debridement and the severity of soft tissue injury had a significant effect on the prognosis of fracture. After the systems pharmacology analysis, six genes, including QPCT, CA1, LDHB, MMP9, UGCG, and HCAR2, were chosen for experimental validation. We found that all six genes in peripheral blood mononuclear cells (PBMCs) and serum were differentially expressed after injury, and five genes (QPCT, CA1, MMP9, UGCG, and HCAR2) were significantly lower in nonunion patients. Further, CA1, MMP9, and QPCT were markedly increased after DR treatment. Conclusion CA1, MMP9, and QPCT are biomarkers of nonunion patients and DR treatment targets. However, HCAR2 and UGCG are biomarkers of nonunion patients but not DR treatment targets. Therefore, our findings may provide valuable information for nonunion diagnosis and DR treatment. Trial registration ISRCTN, ISRCTN13271153. Registered 05 April 2020—Retrospectively registered.

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Section: Discussionmentioning

confidence: 99%

Bioinformatic analysis and experimental identification of blood biomarkers for chronic nonunion

Liu

et al. 2020

J Orthop Surg Res

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“…Molecular tools offer new opportunities for improving diagnostics and predictive medicine. This line of research is based on the detection of molecules involved in bone regeneration, either in peripheral blood or urine, which are used as biomarkers for monitoring the bone healing process ( Chaverri and Vives, 2017 ; Pountos et al, 2013 ). Importantly, the use of a biomarker may be useful for patients at risk of non-union by assisting orthopaedists to establish special measures for early treatment to correct this situation.…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, the use of a biomarker may be useful for patients at risk of non-union by assisting orthopaedists to establish special measures for early treatment to correct this situation. Human research on this topic is limited and methodologically poor, mainly based on cross-sectional and retrospective studies, with small sample size and inconclusive outcomes ( Chaverri and Vives, 2017 ; Pountos et al, 2013 ; Sousa et al, 2015 ; Tatsuyama et al, 2000 ; Hankenson et al, 2014 ). At present, Transforming Growth Factor-Beta 1 (TGF-β1) is one of the most studied molecule in humans ( Zimmermann et al, 2005 ; Zimmermann et al, 2007 ; Sarahrudi et al, 2011 ; Wang et al, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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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Biomarkers of bone healing induced by a regenerative approach based on expanded bone marrow–derived mesenchymal stromal cells

et al. 2019

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Toward the Clinical Use of Circulating Biomarkers Predictive of Bone Union

Cited by 5 publications

References 44 publications

Bioinformatic analysis and experimental identification of blood biomarkers for chronic nonunion

Bioinformatic analysis and experimental identification of blood biomarkers for chronic nonunion

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

Biomarkers of bone healing induced by a regenerative approach based on expanded bone marrow–derived mesenchymal stromal cells

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