21 General introduction and outline of this thesis and reliably on Na[18F]F-PET/CT. Secondly, measurements of pathological bone in FD/ MAS-patients and its relevance in clinical practice will be discussed. Two relevant unmet needs are selected regarding FD/MAS-patients: 1. the need for accurate and reproducible assessment of the FD/MAS-related skeletal burden in primary diagnosis, as other currently used clinical methods show limitations. 2. the need to assess change in FD/MAS-related skeletal burden accurately and reproducibly in follow-up after treatment, e.g., with the RANKL-inhibitor denosumab, in conjunction with clinically relevant measures (pain, quality of life and serum BTMs). This thesis aims to contribute to the evidence of strengths, weaknesses and suggested clinical use of bone-SPECT/CT and Na[18F]F-PET/CT for early detection of benign bone and joint diseases at initial diagnosis and with special interest in followup after surgery in orthopedic indications and after bone remodeling medication in FD/MAS. Quantification of skeletal burden in patients with FD/MAS using Na[18F]F-PET/CT Not all increased tracer uptake on Na[18F]F-PET/CT solely reflects bone disease, let alone FD/MAS. Firstly, extra-osseous uptake is normal in especially the kidneys and urinary bladder due to renal clearance of the radiopharmaceutical. Secondly, Na[18F]F-uptake is not specific to the disease under study, e.g., active growth plates in pediatric patients and osteoarthritis in adults and in elderly patients will demonstrate strongly increased bone turnover and of uptake intensity alone will not discriminate FD/MAS from osteoarthritis. Thirdly, osteoarthritis is particularly prevalent in patients with FD/MAS, not only due to age but also secondary to the deformative nature of FD/MAS. Moreover, osteoarthritis activity may progress over time. Therefore, uptake caused by osteoarthritis is expected to affect intra-patient measurements of skeletal FD-burden. Our studies should describe how to optimize wholebody measurements to include all FD uptake by manual exclusion of nonspecific uptake and extra-osseous uptake when measuring FD. This requires image interpretation combined with knowledge of the radiologic features of alternative diagnoses. Lastly, we will describe the improvements that could be possible in future measurement methodologies. For illustration of the method measuring FD and excluding other irrelevant sites of increased tracer uptake, Figure 3 exemplifies such a measurement. 1