The purpose of this study was 1) to assess the inter-reader reliability in detecting and scoring the inflammatory bone lesions in pediatric patients with chronic nonbacterial osteomyelitis (CNO) by using WB-MRI, and 2) to evaluate the responsiveness of the MRIdetected CNO lesions to pamidronate therapy.Eighty-eight WB-MRI examinations were independently reviewed and scored by two radiologists blinded to clinical details in 32 retrospectively enrolled pediatric patients with CNO. Inflammatory bone lesions, soft tissue abnormality, and bony structural changes were scored before and after pamidronate therapy. Lesion responsiveness was calculated by using standardized response mean and inter-reader reliability was assessed by kappa statistics.There was good to excellent inter-reader agreement for the detection and quantification of bone lesions. After the first cycle of pamidronate in all 32 patients, 96 of the 279 lesions (34%) (after excluding 108 lesions of hand and feet) resolved, while in a subset of 11 patients with two or more cycles, 76% of lesions resolved after the second cycle. Twenty-one (7.5%) lesions worsened and 46 (16.4%) new lesions developed after one cycle in all 32 patients. In these 11 patients, the number of worsened lesions reduced to 2 (2%) and new lesions to 14 (14.9%) after the second cycle as detected on MRI. Vertebral lesions had the highest response to treatment.WB-MRI is a reliable tool for objective quantification and assessment of response to treatment of pediatric CNO bone lesions and could be used to monitor disease activity for clinical and research purposes.