Bone Abstracts

Fibrodysplasia ossificans progressiva (FOP) is a rare, autosomal dominant disorder characterized by heterotopic ossification (HO) in muscles, ligaments and tendons. Flare-ups often precede formation of HO, resulting in immobilized joints. Recently, it has been shown that [18F]NaF PET/CT could identify early ossifying disease activity during flare-ups. HO may progress without signs of flare-up, but its underlying physiology is not understood. We wondered whether [18F]NaF PET/CT could identify this silent progression of FOP. Therefore we analysed [18F]NaF PET/CT follow-up data in a small group of FOP patients during several years and investigated which HO progressed in the absence of flare-up. Intriguingly, we found in 4 out of 5 patients one or more progressive HO lesions related to activity on the [18F]NaF PET/CT scan. Hereby we demonstrated the co-existence of chronic activity of FOP leading to silent progression of HO. In fact in all four late adolescent and young adults we found chronic progression of disease activity without clinical symptoms. The duration of this chronic FOP phase is unknown. But previously we observed in a young patient chronic continuous activity of HO on bone scintigraphy with increasing contracture during her growth over >10 years. This may indicate that HO can be chronic active for a long time. Future drugs should target not only HO formation after flare-ups, but should also stop progression in this chronic phase. In rare bone disease well measurable endpoints are scarce. However inhibition of quantifiable activity in FOP as assessed by [18F]NaF PET/CT scanning could be used as a hard endpoint in drug studies. At this moment this imaging modality is used in one trial (Lumina-1, Regeneron Pharmaceuticals) and will also be used in a new upcoming European trial. During the first decade of life, most children with FOP already develop moderate to severe disabling HO. It is therefore important to study the role of the chronic activity in young people which might be longer after a flare up. At this moment we are developing careful procedures of [18F] NaF PET/CT scanning in young children to study the course of the disease and to develop drug strategies.

Disclosure: Cooperation in clinical trial Lumina-1 of Regeneron Pharmaceuticals.