Circulating microRNAs (c-miRs) show promise as biomarkers. This systematic review explores their potential association with age-related fracture/osteoporosis (OP), osteoarthritis (OA) and sarcopenia (SP), as well as cross-disease association. Most overlap occurred between OA and OP, suggesting potentially shared microRNA activity. There was little agreement in results across studies. Few reported receiver operating characteristic analysis (ROC) and many identified significant dysregulation in disease, but direction of effect was commonly conflicting. c-miRs with most evidence for consistency in dysregulation included miR-146a, miR-155 and miR-98 for OA (upregulated). Area under the curve (AUC) for miR-146a biomarker performance was AUC 0.92, p=0.028. miR-125b (AUC 0.76-0.89), miR-100, miR-148a and miR-24 were consistently upregulated in OP. Insufficient evidence exists for c-miRs in SP. Study quality was typically rated intermediate/high risk of bias. Wide study heterogeneity meant meta-analysis was not possible. We provide detailed critique and recommendations for future approaches in c-miR analyses based on this review.
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