News Release

Key features of chronic nonbacterial osteomyelitis identified in groundbreaking study

Peer-Reviewed Publication

American College of Rheumatology

ATLANTA -- New research presented at ACR Convergence, the American College of Rheumatology's annual meeting, identified key clinical features of chronic nonbacterial osteomyelitis (CNO), which leads to an important step toward the development of much-needed classification criteria for a disease that affects children and young adults worldwide (ABSTRACT #1162).

Chronic nonbacterial osteomyelitis (CNO), also called chronic recurrent multifocal osteomyelitis (CRMO), is a disease that mostly affects children and young adults. Hallmark symptoms include painful swelling of the bones, especially the long bones, but also the pelvis, clavicle and spine.

Currently, there are no classification criteria for CNO. That means rheumatologists, pediatricians and other physicians lack widely accepted sets of defining features of the disease to identify patients for clinical trials and research studies. There are also no validated diagnostic criteria for CNO, which are sets of key disease features used to diagnose these young patients. In this new study, researchers set out to refine the potential items that could be part of classification criteria for pediatric patients with CNO. To do that, they conducted a study that compared clinical, laboratory and imaging features of CNO to features of other diseases that mimic it.

"There is no specific confirmatory test for CNO, and many children need a bone biopsy to exclude cancer and infection," says study co-author Yongdong Zhao, MD, PhD, RhMSUS, Assistant Professor and Director of Ultrasound at Seattle Children's Hospital and its Center for Clinical and Translational Research. "A sensitive and specific classification criteria set will enable researchers to identify appropriate patients to carry out high-quality clinical trials, which physicians with less experience in this potentially debilitating disease need to determine effective treatments."

For this international study, researchers collected clinical and investigational features of CNO from 450 patient cases from 20 medical centers across four continents and seven countries. They also gathered cases of patients who had likely "mimickers" of CNO. All patients included in the study had at least 12 months of medical follow-up unless pathology or labs in mimicker cases confirmed the diagnosis.

They reviewed each patient's case to determine how confident they were that the patient either had CNO or one of its mimicker diseases. The confidence levels used in the study had a cut-off measurement of +/- 2 for "moderately confident." They used 264 CNO and 145 mimicker control cases for the analysis.

When comparing to patients with mimicker conditions, they found a higher percentage of female patients with CNO. They also found that patients with CNO often have intermittent versus continued pain, especially in the neck, back and upper torso, and less commonly have fevers. Another common feature of CNO was swelling of the clavicle, while active arthritis was a less common feature. CNO patients also commonly undergo whole body imaging tests, usually MRIs. Imaging helps to identify other common features of CNO, the study showed.

CNO patients commonly have symmetric patterns of bone lesions, and their disease frequently involves these bones: the thoracic spine, clavicle, pelvis, bilateral femur, bilateral tibia, unilateral fibula and feet. Imaging data collected in the study also showed that signs of malignancy and infection, such as cortical bone disruption, disorganized bone formation, mass structure, marrow infiltrates, and abscess or geographic appearances, are less common in patients with CNO. The study also found that completed and sustained responses to antibiotics are less frequent in young people with CNO.

Using actual patient cases, the study successfully identified key features of CNO that could support the development of the much-needed classification criteria for this disease, the researchers said.

"These results confirmed important features that physicians can look for to distinguish CNO from its mimicker diseases in daily practice using a large international database," says Dr. Zhao. "The next step is to determine the appropriate weight of each criterion by an expert panel using 1000MINDs. A threshold will be set for the new criteria, and another cohort of patients will be used to validate the set. We welcome more collaborators to join us for the collection of a validation cohort."


About ACR Convergence

ACR Convergence, the ACR's annual meeting, is where rheumatology meets to collaborate, celebrate, congregate, and learn. Join ACR for an all-encompassing experience designed for the entire rheumatology community. ACR Convergence is not just another meeting - it's where inspiration and opportunity unite to create an unmatched educational experience. For more information about the meeting, visit, or join the conversation on Twitter by following the official hashtag (#ACR20).

About the American College of Rheumatology

The American College of Rheumatology (ACR) is an international medical society representing over 7,700 rheumatologists and rheumatology health professionals with a mission to empower rheumatology professionals to excel in their specialty. In doing so, the ACR offers education, research, advocacy and practice management support to help its members continue their innovative work and provide quality patient care. Rheumatologists are experts in the diagnosis, management and treatment of more than 100 different types of arthritis and rheumatic diseases.


Comparison of Clinicopathologic and Imaging Features Between Chronic Nonbacterial Osteomyelitis and Its Mimickers: A Multi-national 450 Case-Control Study


Chronic nonbacterial osteomyelitis (CNO)/chronic recurrent multifocal osteomyelitis (CRMO) predominantly affects children and young adults. Classification criteria are not available and diagnostic criteria that have been suggested have not been validated. We previously identified candidate items for the development of classification criteria.


We aimed to refine candidate items for pediatric classification criteria for CNO by comparing clinical, laboratory and imaging features of CNO against mimicking conditions. International multicentre collection of clinical and investigational features of cases with CNO or mimicker diseases with at least 12 months follow-up was conducted through a REDCap online database. Prevalence ratios of each collected item between CNO and mimickers were calculated. A p value of <.05 was considered significant.


450 cases were collected from 20 centers in 7 countries and 4 continents. Cases were filtered based on indicated confidence levels of diagnosis for CNO or mimickers using a cut-off of +/- 2 (moderately confident). 264 (59%) CNO cases and 145 (32%) mimicker controls were used for analysis. 41 (9%) cases were excluded. Key findings are summarized in Table 1. When compared to mimicker diagnoses, CNO patients were predominantly female, more frequently exhibited intermittent versus continued pain (especially of neck, back and upper torso), but less commonly had fever. Clavicular swelling was more common in CNO, while active arthritis was less common as compared to controls. CNO patients more frequently had whole body imaging (usually whole-body MRI). Symmetric patterns of bone lesions were more common in CNO. CNO frequently involved the thoracic spine, clavicle, sternum/manubrium, pelvic bones, bilateral femur, bilateral tibia, unilateral fibula, and foot bones. Imaging features that are concerning for infection or malignancy (including cortical bone disruption, disorganized bone formation, mass structure, marrow infiltrate, abscess or geographic appearance) were less common in CNO. Lastly, complete and sustained response to antibiotic treatment was less frequent in CNO patients.


Using a case-based approach, key features of CNO were identified to support the development of classification criteria. Next steps will include expert panel discussions and a 1000Minds exercise.

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