DKK1 and synovitis: Patients with very early disease have a distinct serum metabolomic profile and synovial fluid cytokine profile when compared with patients with established RA.15 50 Moreover, fibroblasts from very early RA showed increased dickkopf-related protein 1 (DKK-1) expression with the potential to adversely alter bone remodelling; a feature not apparent in fibroblasts from patients with resolving synovitis.51 Collectively, these data strongly support the transitional nature of synovial pathology during the earliest stages of disease development.