23 General introduction and outline of this thesis wrist, in order to answer the research question what the current scientific evidence for bone-SPECT/CT is in these patients, as well as usefulness for clinical application. To assess the value of bone-SPECT/CT in patients with a tarsal coalition with insufficiently explainedpain Chapter 5 was designed to elucidatewhenbone-SPECT/CT is beneficial in patients with tarsal coalitions at primary diagnosis and in follow-up after surgery, by critically illustrating features and by discussing in-depth indications, limitations, relations to other imaging techniques and impact of bone-SPECT/CT on patient care, and by providing a suggested imaging workflow for these patients. Part II of this thesis aims to address the clinically unmet need for accurately localizing FD/MAS-related skeletal burden at primary diagnosis and during follow-up after treatment with denosumab. An observational cohort of FD/MAS-patients that underwent Na[18F]F-PET/CT will be retrospectively analyzed. Chapter 6 primarily answers the research question whether Na[18F]F-uptake using PET/CT at primary diagnosis of FD/MAS could adequately quantify healthy bone metabolism and localized FD skeletal burden in relation to clinical and biochemical parameters used for FD/MAS. Secondary aims consist of comparing normalization for volume of distribution, and determining reproducibility of Na[18F]F-PET/CT uptake parameters in healthy bone and in FD/MAS, and to relate quantified Na[18F]F-uptake to the current imaging standard, the skeletal burden score using bone scintigraphy, to bisphosphonate therapy and pain. Chapter 7 contains our scientific response to a suggested procedure by other authors, hypothesizing possible improvement on our quantification methodology, by correcting for skeletal volume on the corresponding low-dose non-contrast enhanced CT of the Na[18F]F-PET/CT. Chapter 8 describes our analyses on (quantitative) Na[18F]F-PET/CT during follow-up, and the ability of Na[18F]F-PET/CT in capturing treatment-induced skeletal changes and whether this correlated with the clinically relevant serum BTMs and pain reduction. In Chapter 9, two cases of patients with FD/MAS and the response on both plain radiographs and Na[18F]F-PET/CT after treatment with denosumab are presented. Thus, this thesis aims to contribute to scientific evidence in optimizing patienttailored diagnosis for the abovementioned benign bone and joint diseases and aspires to encourage follow-up research in the future. Last, but not least, it hopes to serve as a practical guide in daily practice for medical specialists with interest in the subject of advanced imaging in benign bone and joint disease. 1