First Classification Criteria Proposed for Chronic Osteomyelitis

Marcia Frellick

November 18, 2022

PHILADELPHIA — An international group of researchers has proposed the first classification criteria for chronic nonbacterial osteomyelitis (CNO) and a severe form of it, chronic recurrent multifocal osteomyelitis (CRMO).

CNO/CRMO most frequently affect children and adolescents and can significantly affect quality of life.

Dr Yongdong (Dan) Zhao

Yongdong (Dan) Zhao, MD, PhD, a pediatric rheumatologist at Seattle Children's Hospital, Seattle, Washington, and Seza Ozen, MD, MSc, medical faculty head at Hacettepe University in Ankara, Turkey — members of the expert panel for criteria development — explained the proposed criteria, developed over 6 years, at the American College of Rheumatology (ACR) 2022 Annual Meeting.

They gave examples of the point system that will help researchers correctly classify CNO/CRMO if the criteria are approved by ACR and the European Alliance of Associations for Rheumatology (EULAR).

Dr Melissa Oliver

Melissa Oliver, MD, a pediatric rheumatologist at Riley Children's Hospital and Indiana University School of Medicine in Indianapolis, told Medscape Medical News: "This proposal is important because CNO/CRMO has primarily been a diagnosis of exclusion. There are no specific test or biomarkers for this disease. It can mimic malignancy and infectious osteomyelitis in its presentation, and these must be ruled out thoroughly first."

However, she noted, this can be challenging and can delay diagnosis and treatment.

The classification criteria are novel, she said, because an international collaborative group used a consensus process involving physicians managing CNO and patients or caregivers of children with CNO.

Findings For and Against CNO

Ozen summarized some examples of findings for and against a CNO/CRMO classification.

Dr Seza Ozen

Statistically significant findings in favor of CNO/CRMO, she said, include intermittent bone pain; bone pain in upper torso; swelling of upper torso; presence of symmetric lesions; and presence of adaptive immune cell and/or fibrosis in biopsy.

Conversely, findings against CNO/CRMO include fever; signs of infection by labs; signs of cancer by biopsy; specific abnormal x-ray/CT scan; specific abnormal MRI; or pain resolved with antibiotics alone.

Zhao described a point system with a threshold of 55 points for classification of CNO/CRMO.

He gave actual examples from the registry to demonstrate high and low probability of CNO/CRMO.

Pro-CNO Example

The first was a boy, age 7 years 10 months, who had a year and a half of pain in his back and legs, but no fever. Pain was constant, waxing and waning. He had a personal and family history of psoriasis and was tender to palpation at multiple sites. Labs were normal and bone biopsy and vitamin C tests were not done; imaging findings showed multiple bones were affected. There was no antibiotic treatment.  

That patient was scored 81, much higher than the threshold of 55 and would be classified as having CNO.

Non-CNO Example

Conversely, the following example of a patient would score 47 — under the threshold — and would not be classified as having CNO.

That patient was an 11-year-old boy who had 2 months of pain in his right thigh with no fever. The pain was constantly waxing and waning. He was tender to palpation at only his right thigh without swelling. Labs were normal. He had no coexisting conditions. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were not measured, and no vitamin C test was performed. Imaging showed one right femur lesion on a PET-CT scan. There was no antibiotic treatment, and a bone biopsy culture showed malignancy, but no inflammation or fibrosis.

Zhao said the mimickers most likely to be misclassified are vitamin C deficiency; hypophosphatasia; benign bone tumor, such as osteogenic osteoma; and a malignancy with normal labs and multifocal pattern of bone lesions.

The classification criteria will be "extremely helpful to diagnose patient with CNO/CRMO earlier," said Oliver, who helped develop the criteria.

"The goal is that the proposed classification criteria will be used by all physicians to diagnose suspected CNO patients earlier and refer to a rheumatologist earlier so that appropriate therapies will not be delayed."  

The group will seek ACR and EULAR endorsement, and if granted, work toward widespread implementation. The criteria will allow researchers to have a more homogenous study population for future clinical trials, Zhao said.

Zhao, Ozen, and Oliver declared no relevant financial relationships. Oliver helped develop the proposed guidelines.

American College of Rheumatology (ACR) 2022 Annual Meeting. Presented November 12, 2022.

Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, and, and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick.

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