Chronic nonbacterial osteomyelitis: current perspectives in pediatric practice

Chronic nonbacterial osteomyelitis (CNO) is a rare, autoinflammatory bone disorder that predominantly affects children and adolescents. The disease covers a broad clinical spectrum ranging from isolated bone lesions to its severe multifocal form, chronic recurrent multifocal osteomyelitis (CRMO). Although its exact pathogenesis remains elusive, recent advances highlight a pivotal role of innate immune dysregulation, particularly involving imbalanced cytokine signaling. These abnormalities drive sterile bone inflammation and osteoclast activation, leading to bone pain and lytic or sclerotic lesions. CNO remains a diagnosis of exclusion owing to the lack of specific biomarkers or standardized diagnostic criteria; however, the recently developed European Alliance of Associations for Rheumatology/American College of Rheumatology (EULAR/ACR) classification framework represents an important step toward uniformity in research and clinical trials. Whole-body magnetic resonance imaging has emerged as the imaging modality of choice for diagnosis and monitoring, while biopsy is reserved for atypical or unifocal cases. Management is empirical and guided by disease severity, with nonsteroidal anti-inflammatory drugs as first-line therapy, followed by corticosteroids, disease-modifying antirheumatic drugs, bisphosphonates, and biologic agents such as tumor necrosis factor (TNF) inhibitors in refractory cases. New insights into the interleukin (IL)-1, IL-6, and IL-17/23 pathways have opened avenues for targeted therapies, including Janus kinase (JAK) inhibitors, in difficult-to-treat patients. Despite earlier perceptions of a benign course, long-term follow-up indicates a risk of relapses and structural complications, underscoring the need for early recognition and multidisciplinary management. Ongoing international collaborations are expected to refine diagnostic precision and optimize treatment strategies to improve outcomes in pediatric CNO.