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Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disease that most commonly affects children and adolescents causing significant pain and damage to bones. The absence of diagnostic criteria and biomarkers, an incomplete understanding of the molecular pathophysiology, and lack of evidence from randomized and controlled trials make the diagnosis and care challenging. This review provides an overview of the clinical and epidemiological features of CNO and displays diagnostic challenges and how they can be addressed following strategies used internationally and by the authors. It summarizes the molecular pathophysiology, including pathological activation of the NLRP3 inflammasome and IL-1 secretion, and how these observations can inform future treatment strategies. Finally, it provides a summary of ongoing initiatives aiming at classification criteria (ACR/EULAR) and outcome measures (OMERACT) that will enable the generation of evidence through clinical trials. Scientific efforts have linked molecular mechanisms to cytokine dysregulation in CNO, thereby delivering arguments for cytokine blocking strategies. Recent and ongoing collaborative international efforts are providing the basis to move toward clinical trials and target directed treatments for CNO that find approval by regulatory agencies.

Classification and management strategies for paediatric chronic nonbacterial osteomyelitis and chronic recurrent multifocal osteomyelitis