Use of Omics Data in Fracture Prediction; a Scoping and Systematic Review in Horses and Humans

SIMPLE SUMMARY: Despite many recent advances in imaging and epidemiological data analysis, musculoskeletal injuries continue to be a welfare issue in racehorses. Omics studies describe the study of protein, genetic material (both DNA and RNA, including microRNAs—small non-coding ribonucleic acids) and metabolites that may provide insights into the pathophysiology of disease or opportunities to monitor response to treatment when measured in bodily fluids. As these fields of study are scientifically complex and highly specialised, it is timely to perform a review of the current literature to allow for the design of robust studies that allow for repeatable work. Systematic reviews have been introduced into the medical literature and are a methodological way of searching for relevant papers followed by critical review of the content and a detection of biases. The objectives of the current systematic review were to identify and critically appraise the literature pertaining to microRNA (miRNA) and their target genes that are correlated with stress fractures in racehorses and humans. The object was to define a panel of miRNAs and their target genes as potential biomarkers in either horses or human subjects. The online scientific databases were searched and a reviewed was performed according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. MicroRNA profiling studies in horses continue to emerge, but as of yet, no miRNA profile can reliably predict the occurrence of fractures. It is very important that future studies are well designed to mitigate the effects of variation in sample size, exercise and normalisation methods. ABSTRACT: Despite many recent advances in imaging and epidemiological data analysis, musculoskeletal injuries continue to be a welfare issue in racehorses. Peptide biomarker studies have failed to consistently predict bone injury. Molecular profiling studies provide an opportunity to study equine musculoskeletal disease. A systematic review of the literature was performed using preferred reporting items for systematic reviews and meta-analyses protocols (PRISMA-P) guidelines to assess the use of miRNA profiling studies in equine and human musculoskeletal injuries. Data were extracted from 40 papers between 2008 and 2020. Three miRNA studies profiling equine musculoskeletal disease were identified, none of which related to equine stress fractures. Eleven papers studied miRNA profiles in osteoporotic human patients with fractures, but differentially expressed miRNAs were not consistent between studies. MicroRNA target prediction programmes also produced conflicting results between studies. Exercise affected miRNA profiles in both horse and human studies (e.g., miR-21 was upregulated by endurance exercise and miR-125b was downregulated by exercise). MicroRNA profiling studies in horses continue to emerge, but as yet, no miRNA profile can reliably predict the occurrence of fractures. It is very important that future studies are well designed to mitigate the effects of variation in sample size, exercise and normalisation methods.