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Classification and management strategies for paediatric chronic nonbacterial osteomyelitis and chronic recurrent
Shabnam Singhal1,2, Caren Landes1,3, Rajeev Shukla4
1Department of Paediatric Rheumatology, Alder Hey Children's NHS Foundation Trust Hospital, Liverpool, UK.
Insights
Chronic non-bacterial osteomyelitis (CNO) is a challenging autoinflammatory bone disease in children. Understanding its molecular basis and developing clinical trials are key to improving diagnosis and targeted treatments.
Area of Science:
- Pediatric rheumatology
- Autoinflammatory diseases
- Bone disorders
Background:
- Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disease affecting children and adolescents.
- Significant challenges exist in CNO diagnosis and management due to a lack of criteria, biomarkers, and clinical trial data.
- The molecular pathophysiology of CNO, including inflammasome activation, is not fully understood.
Purpose of the Study:
- To review the clinical and epidemiological features of CNO.
- To discuss diagnostic challenges and potential solutions.
- To summarize the molecular pathophysiology and its implications for treatment.
Main Methods:
- Literature review of clinical and epidemiological data on CNO.
- Summary of molecular pathophysiology, focusing on NLRP3 inflammasome and IL-1.
- Overview of ongoing initiatives for classification criteria and outcome measures.
Main Results:
- CNO presents diagnostic and management challenges.
- NLRP3 inflammasome activation and IL-1 secretion are implicated in CNO pathophysiology.
- International efforts are underway to establish classification criteria and outcome measures.
Conclusions:
- Improved understanding of CNO pathophysiology supports cytokine-blocking therapies.
- Ongoing initiatives aim to facilitate clinical trials and regulatory approval for CNO treatments.
- Collaborative efforts are paving the way for evidence-based, targeted treatments for CNO.
Introduction:
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.
Areas Covered:
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.
Expert Opinion:
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.
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