EULAR and ACR unveil the first validated framework to classify chronic nonbacterial osteomyelitis in children, marking a turning point in care and research.
A new international classification framework for chronic nonbacterial osteomyelitis in children has been developed and validated by the European Alliance of Associations for Rheumatology and the American College of Rheumatology, in a move hailed as a “milestone” in paediatric rheumatology.
Published in the Annals of the Rheumatic Diseases, the new EULAR/ACR criteria aim to improve recognition, research and clinical trial enrolment for the rare auto-inflammatory bone disorder.
CNO affects children and adolescents, often leading to long-term pain, disability and skeletal deformities if left untreated. Its causes are still unknown. Until now, no formal classification criteria existed. The resulting framework reflects current views about the disease and demonstrates high specificity and good sensitivity.
“The new EULAR/ACR classification criteria for CNO require typical radiographic or magnetic resonance imaging findings and bone pain as an obligatory entry criterion and exclusion criteria of malignancy, infection, vitamin C deficiency and hypophosphatasia, followed by additive weighted criteria in five clinical (site of bone lesions, pattern of bone lesions, age at onset, coexisting conditions [and] fever) and four pathology/laboratory domains (bone biopsy findings if done, anaemia, C-reactive protein level and erythrocyte sedimentation rate),” the authors wrote.
“A total score ≥ 55 is required for classification as CNO. The new criteria had a sensitivity of 82% and specificity of 98% in the validation cohort.”
The researchers said the endorsed classification criteria for paediatric CNO represented a “milestone in CNO care and research”.
“A key strength of the criteria is that patients can be classified accurately as having CNO, even in the absence of bone biopsies,” they wrote.
“However, it is important to reiterate that classification criteria are not diagnostic criteria and that biopsies may be essential in certain settings to exclude differential diagnoses of CNO.”
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Because of its slow onset and variable presentation, CNO is difficult to characterise and diagnose, and there is limited awareness in clinical practice.
Until now, there have been no classification criteria for this rare disease. But such tools are important to help characterise the epidemiology and natural history, and to enrol the right patients in clinical trials–ensuring consistency between different trial populations.
To address this, EULAR and ACR set out to develop the first classification criteria for paediatric CNO, combining international expert consensus and data-driven methods –and also including the patient’s perspective.
To ensure the findings had broad relevance, the authors collected data from 31 centres across six continents, including Australia.
The international collaboration had four key phases. First, candidate items were proposed based on a survey of paediatric rheumatologists. Following this, criteria definition and reduction was achieved, and the group then performed criteria weighting using multicriteria decision analysis.
Finally, weights and threshold scores were refined in a development cohort of 441 patients and validated in a separate group of514 patients.
The new criteria have two initial steps. First, for a classification of CNO, children must be under the age of 18, have bone pain or musculoskeletal limitations that have been going on for at least six weeks, and abnormal findings on X-ray or advanced imaging such as MRI.
Secondly, they must not have any evidence of malignancy, infection, vitamin C deficiency or hypophosphatasia.
If these two initial steps are satisfied, a score is then calculated across nine domains –five of which are clinical, and the remaining four from pathology and laboratory measures – with a total score of at least 55 required for classification as CNO. The selected items are easy to apply in children without the absolute requirement for a bone biopsy.
“We are deeply grateful for the invaluable support and guidance of the EULAR and ACR criteria committee throughout this process” said Professor Yongdong Zhao, lead author on the paper and director of the Clinical CNO Program at Seattle Children’s Hospital and the University of Washington School of Medicine, USA.
“Ultimately, this validated classification criteria provides a crucial foundation for our future clinical trials aimed at developing new treatments and improving outcomes for patients.”
The EULAR 2025 Congress was held in Barcelona earlier this month.
