Thesis

153 Quantifying skeletal burden in fibrous dysplasia using Sodium Fluoride PET/CT Introduction Fibrous dysplasia (FD), including McCune-Albright syndrome (MAS), is a rare benign disorder caused by a somatic post-zygotic mutation in the G-nucleotide binding protein alpha sub unit (GNAS1) on chromosome 20q13.32 [1, 2]. Clinical presentation ranges from an accidental finding to extensive bone disease and extraskeletal manifestations, causing considerable impairment [3]. In monostotic fibrous dysplasia (MFD), one single bone is affected, comprising the majority of FD patients. In the polyostotic form (PFD), multiple bones are affected [4]. In FD, normal bone is being replaced by fibrous tissue with structure and quality inferior to healthy bone, leading to bone deformities, bone pain and increased risk of bone fractures [3, 4]. This increased bone formation can be reflected by an increase in serum alkaline phosphatase (ALP) and procollagen type 1 N-terminal propeptide (P1NP), whereas the observed increased bone resorption is reflected by an increase in serum telopeptides of type 1 collagen (CTX). Fibroblast growth factor 23 (FGF-23) is also used as a biomarker for disease activity as this is produced by FD lesions causing renal phosphate wasting [5]. In order to assess the severity of FD planar bone scintigraphy is used. This modality is useful in clinical practice as an adjunct to determine the skeletal burden of FD, with the Skeletal Burden Score (SBS) first postulated by Collins, et al. in 2005 [2]. According to this publication, all measured bone metabolism biomarkers (bone formation markers: ALP, P1NP, osteocalcin and bone resorption marker: pyridinoline) correlated with disease burden as measured with the SBS [2]. However, this instrument has several limitations. First, SBS is based on planar imaging, while the human skeleton is a three-dimensional (3D) structure, and especially the thorax, spine and pelvis are 3D regions and are frequently affected by FD. 3D cross-sectional imaging provides more precise information on the extent of involved skeletal structures and thus skeletal burden. Single photon emission computed tomography (SPECT)-imaging could result in improvement, nonetheless, whole body SPECT/CT is seldomly performed as the acquisition would be very time-consuming. Second, the spatial resolution of both planar bone scintigraphy and SPECT is inferior to positron emission tomography (PET). Third, the used PET-radiopharmaceutical has a shorter incubation time when compared to whole body SPECT. Finally, SBS determination is semiquantitative and is limited to a weighted sum of the per-segment estimation of the percentage of affected normal bone volume. The weighting factors used are based on average representation of that segment to an adult skeleton, which might be an underestimation for FD-affected segments that often show expansile lesions causing considerable pain complaints, e.g. in the ribs. Both PET and SPECT are now 6

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