Evolution of heterotopic bone in fibrodysplasia ossificans progressiva: An [F]NaF PET/CT study.

Fibrodysplasia ossificans progressiva (FOP) is a rare, autosomal dominant disorder characterized by heterotopic ossification (HO) in muscles, ligaments and tendons. Flare-ups often precede the formation of HO, resulting in immobilization of joints. Due to progression of the disease without signs of a flare-up, co-existence of a chronic progression of HO has been postulated, but conclusive evidence is lacking. Recently, it has been shown that [F]NaF PET/CT is able to identify early ossifying disease activity during flare-ups. Therefore, the purpose of the present study was to assess whether [F]NaF PET/CT might also be able to identify the possible presence of chronic progressive HO in FOP. A total of thirteen [F]NaF PET/CT scans from five FOP patients were analysed. Scans were acquired over a period of 0.5 to 2 years. Volumes of HO and standardized uptake values (SUV) were obtained based on manual segmentation of CT images. SUV values, defined as the average SUV value of a 1 mL sphere containing the hottest voxel pixels, were obtained. Two out of five patients experienced ≥1 active clinical flare-ups at the time of the [F]NaF PET/CT scan. In addition, in four out of five patients, serial scans showed radiological progression of HO (3 to 8 cm), as assessed by CT volume, in the absence of a clinical flare-up. This volumetric increase was present in 6/47 (12.8%) of identified HO structures and, in all cases, was accompanied by increased [F]NaF uptake, with SUV ranging from 8.4 to 17.9. In conclusion, HO may progress without signs of a flare-up. [F]NaF PET/CT is able to identify these asymptomatic, but progressive HO lesions, thereby demonstrating the presence of chronic activity in FOP. Consequently, future drugs should not only target new HO formation, but also this chronic HO progression.