Chaverri Daniel, Vivas Daniel, Gallardo-Villares Santiago, Granell-Escobar Fernando, Pinto Javier A, Vives Joaquim
Orthopaedic Surgery and Traumatology Department, ASEPEYO Sant Cugat Hospital, Avinguda Alcalde Barnils, 54-60, Sant Cugat del Vallès, 08174 Barcelona, Spain.
Servei de Teràpia Cel·lular, Banc de Sang i Teixits, Edifici Dr. Frederic Duran i Jordà, Passeig Taulat, 116, 08005 Barcelona, Spain.
Bone Rep. 2021 Dec 9;16:101157. doi: 10.1016/j.bonr.2021.101157. eCollection 2022 Jun.
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.
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).
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 ( = 0.005) and TGF-β2 ( = 0.02).
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.
假关节或骨不连是一种骨折并发症，发生率为5%-10%，最常发生于长骨干。目前，这种并发症的治疗需要通过复杂的外科手术来解决，这是骨科和创伤外科医生所关注的问题。使用生物标志物来诊断有骨不连风险的患者，将有助于我们制定早期矫正治疗的特殊措施。
对20例诊断为长骨非肥大性假关节的患者进行前瞻性探索性试验研究，这些患者接受了自体骨移植或由骨髓间充质基质细胞组成的组织工程产品的手术治疗。对患者进行12个月的随访，并采集血浆样本，以确定入组时以及术后1周、2周、1个月、2个月、3个月、6个月和12个月时转化生长因子β1和β2（分别为TGF-β1和TGF-β2）的循环水平。通过断层扫描愈合评分（TUS）评估放射学骨愈合情况。
测定了20例患者的TGF-β1和TGF-β2基础水平（分别为26,702±14,537 pg/mL和307.8±83.1 pg/mL）。其中3例退出研究，因此对17例患者进行了完整随访（9例成功愈合，8例未愈合）。在第12个月时，骨愈合组和骨不连组在TGF-β1（=0.005）和TGF-β2（=0.02）方面均发现有统计学显著差异。
TGF-β1和TGF-β2是与骨再生临床证据相关的生物标志物，可用于监测患者，尽管干预后的早期预测价值需要与其他分子联合进一步研究。
