Background: Chronic nonbacterial osteomyelitis (CNO) is a rare disease spectrum, which lacks biomarkers for disease activity. Sodium fluoride positron emission tomography ([¹⁸F]NaF-PET/CT) is a sensitive imaging tool for bone diseases and yields quantitative data on bone turnover. We evaluate the capacities of [¹⁸F]NaF-PET/CT to provide structural and functional assessment in adult CNO.
Methods: Cross-sectional study among 43 adult CNO patients and 16 controls (patients referred for suspected, but not diagnosed as CNO) undergoing [¹⁸F]NaF-PET/CT at our expert clinic. Structural features were compared between patients and controls, and maximal standardized uptake values(SUV_max (g/ml)) were calculated for bone lesions, soft tissue/joint lesions, and reference bone. SUV_max was correlated with clinical disease activity in patients. 
Results: Manubrial and costal sclerosis/hyperostosis, and calcification of the costoclavicular ligament emerged core structural features associated with CNO as visualized by [¹⁸F]NaF-PET/CT. SUV_max of CNO lesions was higher compared to in-patient reference bone (mean paired difference 11.4, 95%CI9.4-13.5, p<0.001) and controls (mean difference 12.4, 95%CI9.1-15.8, p<0.001). Highest SUV_max values were found in soft tissue and joint areas like the costoclavicular ligament and manubriosternal joint, and these correlated with erythrocyte sedimentation rate in patients (correlation coefficient 0.546, p<0.002).
Conclusion: [¹⁸F]NaF-PET/CT is a promising imaging tool for adult CNO, allowing for detailed structural evaluation of its typical bone, soft-tissue and joint features. At the same time, [¹⁸F]NaF-PET/CT yields quantitative bone remodeling data that represent the pathologically increased bone turnover and the process of new bone formation. Further studies should investigate the application of quantified [18F]NaF-uptake as a novel biomarker for disease activity in CNO, and its utility to steer clinical decision-making.