17 General introduction and outline of this thesis 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 [15]. These serum bone turnover markers (BTMs) are used in assessment of FD-burden at diagnosis and follow-up, as they readily available and inexpensive, but above all able to reflect clinically relevant systemic bone changes. However, these serum measurements are incapable of characterizing the disease on a lesional level, thus not always reflecting clinical burden. An ideal instrument could impact clinical decisions by pinpointing location (intra-, juxta-, or extra-articular, craniofacial, or a less hampering site), and different characteristics of FD-lesions causing individually heterogeneous burden and response to treatment. Secondly, clinicians might encounter FD/MAS-patients with normal(ized) serum BTMs and remaining or recurrent complaints, needing an objective alternative measurement of FD-burden or complication. Planar bone scintigraphy with semiquantitative per-segment estimation, called Skeletal Burden Score (SBS), is only partially able to meet demands for estimating skeletal FD-burden, as discussed below in more detail. Therefore, these specialists desire a new reliable technique to assess usefulness and efficacy of novel therapy (denosumab) during follow-up. Lastly, although medical intervention may slow down the pace of bone deformation, the acquired deformations are still irreversible with medication alone. When deformations lead to facial distortion, reconstructive surgery may be needed, and, in severely weakened bone, orthopaedic surgery may be required to prevent or repair (threatening) fractures. The surgical aspects in FD/MAS are beyond the scope of this thesis, however. Current imaging of FD/MAS and its limitations Different radiological imaging techniques show varying accuracy for detection of different benign bone and joint diseases. Widely available, plain radiographs (X-rays) are often used as first-line imaging at relatively low cost and radiation exposure, with sensitivity being locally adequate in suspected fibrous dysplasia (FD/MAS) in especially the extremities. In complex 3D-bone structures, however, such as the spine or facial bones, plain radiographs have limited sensitivity and they are also less suitable for total skeletal imaging. Of the advanced radiological techniques, CT performs well in reflecting the anatomy of bony structures but lacks sensitivity for early detection of pathophysiological changes of the bone and for differentiating active and nonactive disease. On CT, large enough anatomical changes (sclerosis) 1