Unravelling Heterotopic Ossification in FOP: Its development, progression and persistence

The aim of the work described in this thesis was to gain more insight in the development, progression and complications of heterotopic ossification (HO) in fibrodysplasia ossificans progressiva (FOP). Knowledge about the course of HO is scarce, despite the discovery of a causative genetic mutation in 2006. There are several reasons for this poor understanding of HO, such as the contraindication of invasive techniques to study HO as it may cause exacerbation of disease; the lack of a representative mouse model until very recently, and the rarity of the disease. As a (blood)marker to measure disease activity was not available at the onset of the work described in this thesis, the main purpose was to investigate whether imaging techniques could play a role. More specifically, the use of [18F] sodium fluoride (NaF) Positron Emission Tomography (PET) / Computed tomography (CT) was investigated as, at least in theory, thistechnique can be used to visualize and measure metabolic activity of bone. In addition, the additional diagnostic value of Magnetic Resonance Imaging (MRI) in FOP was studied. Both these imaging techniques were used to investigate whether FOP disease is only active during flare-ups, the course of FOP disease activity, and whether there are different developmental stages of HO. In addition, effects of different (traumatic) therapies on HO development were evaluated. The structure of matured HO was studied using a novel imaging technique, HRpQCT, and, finally, effects of progressive HO on vital organs were evaluated using sequential pulmonary function tests.