Prognostic and Therapeutic Potential of Micrornas for Fracture Healing Processes and Non‐union Fractures: A Systematic Review

Abstract Background Approximately 10% of all bone fractures result in delayed fracture healing or non‐union; thus, the identification of biomarkers and prognostic factors is of great clinical interest. MicroRNAs (miRNAs) are known to be involved in the regulation of the bone healing process and may serve as functional markers for fracture healing. Aims and methods This systematic review aimed to identify common miRNAs involved in fracture healing or non‐union fractures using a qualitative approach. A systematic literature search was performed with the keywords ‘miRNA and fracture healing’ and ‘miRNA and non‐union fracture’. Any original article investigating miRNAs in fracture healing or non‐union fractures was screened. Eventually, 82 studies were included in the qualitative analysis for ‘miRNA and fracture healing’, while 19 were selected for the ‘miRNA and fracture non‐union’ category. Results and conclusions Out of 151 miRNAs, miR‐21, miR‐140 and miR‐214 were the most investigated miRNAs in fracture healing in general. miR‐31‐5p, miR‐221 and miR‐451‐5p were identified to be regulated specifically in non‐union fractures. Large heterogeneity was detected between studies investigating the role of miRNAs in fracture healing or non‐union in terms of patient population, sample types and models used. Nonetheless, our approach identified some miRNAs with the potential to serve as biomarkers for non‐union fractures, including miR‐31‐5p, miR‐221 and miR‐451‐5p. We provide a discussion of involved pathways and suggest on alignment of future research in the field.