Background/Purpose: Chronic nonbacterial osteomyelitis (CNO) is an inflammatory bone disease that causes pain, disability, and sometimes permanent skeletal damage. MRI allows for visualization of bone edema, soft tissue inflammation (STI), periosteal reaction (PR), and characteristics of bone damage, such as growth plate bony bar formation and vertebral collapse. However, no standard MRI-based outcomes have been validated in CNO. This retrospective study aimed to assess changes in CNO activity and damage after tumor necrosis factor alpha inhibitor (TNFi) and methotrexate therapy using a standard MRI scoring method. 

Methods: Children 2-18 years of age with CNO were included if paired MRI scans were performed ≤ 2 months prior to and ≥ 2 months after TNFi initiation. Clinical and laboratory data before and after TNFi therapy were recorded. Unique inflammatory lesions, bone edema severity, STI severity, total lesion number with PR, total lesion number with hyperostosis, bony bar severity, vertebral compression severity, and the number of inflamed joints were recorded by a single radiologist (NC). The Wilcoxon matched pairs signed-ranks test was used to compare changes after TNFi. 

Results: Nine CNO patients treated with TNFi met inclusion criteria. All received infliximab (IFX) and concomitant methotrexate (MTX). All nine (6 females) were Caucasian.  Mean age was 12 ± 4 years. Seven patients previously received antibiotics, NSAIDs, prednisone, bisphosphonate, and/or MTX. The median duration between diagnosis and initiation of IFX was 6.8 months (range: 0.5-19.3). Baseline MRI was obtained 1.0 ± 0.7 months prior to IFX and the follow up MRI was obtained 6.7 ± 3.7 months later. Paired site-specific scans were obtained in 6, and whole body scans in 3 patients.  The mean dose of IFX was 8.1 ± 1.9 mg/kg, every 4-8 weeks. Five of six patients received zoledronic acid for vertebral lesions. The numbers of patients with lesions at specific sites were:  spine (5), pelvis (6), clavicle (2), long bone (4), and mandible (1). At the visit closest to the follow up MRI, significant reductions were seen in the median pain score (4 to 0, p<0.01), patient global assessment (3 to 0, p<0.01), physician global assessment (2 to 0, p<0.01), and Childhood Health Assessment Questionnaire (0.25 to 0, p=0.02). There were significant reductions in the erythrocyte sedimentation rate (15 to 5 mm/hour, p=0.01) and C reactive protein levels (0.8 to 0.5 mg/dL, p=0.03).  Significant decreases in the median total inflammatory lesion number (5 to 2, p=0.03) and maximum bone edema score (2.2 to 1.3, p=0.02) were observed. Maximum STI score and inflamed joint count decreased, but not significantly. Periosteal reaction (n=2) and hyperostosis (n=1) resolved. Skeletal damage severity, including bony bar formation and vertebral compression, did not progress.

Conclusion: In this retrospective study, IFX and MTX with or without zoledronic acid for CNO resulted in significant clinical and radiographic improvement.  Standard MRI assessment demonstrated reductions in active bone lesions and bone edema severity without worsening of spine or growth plate damage. Prospective studies are needed to assess the reliability and validity of standardized MRI protocols.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/methotrexate-and-infliximab-with-or-without-zoledronic-acid-improve-disease-activity-and-prevent-damage-progression-in-chronic-nonbacterial-osteomyelitis/