Perut Francesca, Roncuzzi Laura, Gómez-Barrena Enrique, Baldini Nicola
Biomedical Science and Technologies and Nanobiotechnology Laboratory, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy.
Department of Orthopedic Surgery and Traumatology, Hospital Universitario La Paz-IdiPAZ, 28046 Madrid, Spain.
J Clin Med. 2024 Apr 17;13(8):2333. doi: 10.3390/jcm13082333.
: Fracture healing is a very complex and well-orchestrated regenerative process involving many cell types and molecular pathways. Despite the high efficiency of this process, unsatisfying healing outcomes, such as non-union, occur for approximately 5-10% of long bone fractures. Although there is an obvious need to identify markers to monitor the healing process and to predict a potential failure in callus formation to heal the fracture, circulating bone turnover markers' (BTMs) utility as biomarkers in association with radiographic and clinical examination still lacks evidence so far. : A systematic review on the association between BTMs changes and fracture healing in long bone non-union was performed following PRISMA guidelines. The research papers were identified via the PubMed, Cochrane, Cinahl, Web of Science, Scopus, and Embase databases. Studies in which the failure of fracture healing was associated with osteoporosis or genetic disorders were not included. : A total of 172 studies were collected and, given the inclusion criteria, 14 manuscripts were included in this review. Changes in circulating BTMs levels were detected during the healing process and across groups (healed vs. non-union patients and healthy vs. patients with non-union). However, we found high heterogeneity in patients' characteristics (fracture site, gender, and age) and in sample scheduling, which made it impossible to perform a meta-analysis. : Clinical findings and radiographic features remain the two important components of non-union diagnosis so far. We suggest improving blood sample standardization and clinical data collection in future research to lay the foundations for the effective use of BTMs as tools for diagnosing non-union.
骨折愈合是一个非常复杂且精心编排的再生过程，涉及多种细胞类型和分子途径。尽管这个过程效率很高，但仍有大约5%-10%的长骨骨折会出现诸如骨不连等不尽人意的愈合结果。虽然显然需要识别标志物来监测愈合过程并预测骨痂形成愈合骨折的潜在失败情况，但迄今为止，循环骨转换标志物（BTMs）作为与影像学和临床检查相关的生物标志物的效用仍缺乏证据。
按照PRISMA指南，对长骨骨不连中BTMs变化与骨折愈合之间的关联进行了系统评价。通过PubMed、Cochrane、Cinahl、科学网、Scopus和Embase数据库识别研究论文。骨折愈合失败与骨质疏松症或遗传疾病相关的研究未被纳入。
共收集到172项研究，根据纳入标准，本评价纳入了14篇手稿。在愈合过程中以及不同组之间（愈合患者与骨不连患者、健康人与骨不连患者）检测到了循环BTMs水平的变化。然而，我们发现患者特征（骨折部位、性别和年龄）以及样本安排存在高度异质性，这使得无法进行荟萃分析。
迄今为止，临床发现和影像学特征仍然是骨不连诊断的两个重要组成部分。我们建议在未来研究中改进血样标准化和临床数据收集，为有效利用BTMs作为诊断骨不连的工具奠定基础。
