Chronic Non-Bacterial Osteomyelitis (CNO) in a Tertiary Center in Southern Italy: Response to Treatment and Outcome Stratification

Abstract

Background/Objectives: Chronic non-bacterial osteomyelitis (CNO) is a rare autoinflammatory disease characterized by chronic sterile uni- or multifocal osteomyelitis. The treatment of CNO is mostly empirical and the outcome of the disease has not yet been standardized. The aims of this study were to correlate clinically active lesions with radiological signs of inflammation and to evaluate the outcomes in terms of symptoms and radiological signs with Whole Body Magnetic Resonance Imaging (WB-MRI) based on the treatment line used. Methods: A retrospective, observational cohort study of 20 CNO patients, recruited from a single tertiary center in southern Italy, was conducted. Patients included in the study were treated based on the "step-up" approach and were guided by the "treat-to-target" strategy as well as by the response to therapy. The outcome measure was stratified into four different groups, defined by a "Delphy consensus", depending on the symptoms and the presence of bone lesions in WB-MRI, compared with the therapy carried out. Results: Pain was the most common presenting symptom of the disease. Only 15% of our patients reported long-term complications. WB-MRI was performed for each patient both at diagnosis and during follow-up. At onset, the site most affected by the disease was the tibia. All patients who reached a 5-year follow-up (30%, n = 6) achieved a complete disease remission. Conclusions: The standardized "step-up" treatment approach in our cohort proved effective in disease management with disease control or remission in nearly 90% of patients at one year from diagnosis.

Keywords: autoinflammatory disorders; bone pain; chronic non-bacterial osteomyelitis (CNO); chronic recurrent multifocal osteomyelitis (CRMO); outcome; pain; therapy; whole-body magnetic resonance imaging (WB-MRI).

Figure 1

Radiographic images. (A) Right clavicular lesion;(B) right tibial osteolytic lesion.

Figure 2

T2 STIR and T1 TSE sequences in the coronal plane: (A1–D2) STIR sequence in the sagittal plane of the spine; (E) STIR hyperintensity and T1 hypointensity are suggestive of bone marrow edema; (A1,A2) edema of the left clavicle in T2 STIR and T1 hypointensity; (B1,B2) edema of the greater trochanters in T2 STIR and T1 hypointensity; (C1,C2) edema of the proximal metaphysis and diaphysis of tibias in T2 STIR and T1 hypointensity; (D1,D2) edema of the distal metaphysis and epiphysis of the right tibia in T2 STIR and T1 hypointensity; (E) edema of two dorsal vertebral bodies in T2 STIR.

Figure 3

The histology of three cases (bone needle biopsies): (A,B) bone marrow with normal cellularity by age (“very early stage CNO”); (C,D) normal bone marrow associated with widespread sinusoidal dilatation (“early stage CNO”); (E,F) bone marrow with remarkable hypocellularity replaced by marked fibrosis, mild chronic inflammation and with accentuated remodeling of the bone trabeculae (“late stage CNO”).

Figure 4

T2 STIR and T1 TSE sequences in the coronal plane. Right clavicle involvement in a CNO patient before and after pamidronate treatment. (A1,A2) Clavicle edema, at T0 pre-pamidronate in T2 STIR and T1 hypointensity; (B1,B2) regression of clavicle edema, at T12 post-pamidronate in T2 STIR and T1 hypointensity.

Figure 5

STIR sagittal sequences of the spine. D6 and D9: vertebral involvement in a CNO patient before and after pamidronate treatment. (A) D6 and D9 vertebral edema, MRI-WB T0 pre-pamidronate; (B) regression of bone marrow edema at T12 follow-up post-pamidronate.