Thesis

195 Denosumab reduces lesional Fluoride skeletal burden on Na[18F]F PET-CT Quantification of FD burden using serum biomarkers and correlation with Na[18F]F PET-CT at baseline and at first follow-up BTMs decreased significantly after start of bone remodeling therapy (n=15 patients, 30 scans): ALP 119 IU/L (82-143 IU/L) vs 84 IU/L (64-106 IU/L), p=0.020; P1NP: 82 ng/mL (51-237ng/mL) vs 55 ng/mL (34-112 ng/mL, p=0.023), Figure 4. Baseline SBS (representing the segmented fraction of the affected skeleton on scintigraphy) showed poor correlation with BTMs (p=0.671 for ALP and p=0.486 for P1NP). SUVpeak on Na[ 18F]F PET-CT did not correlate to ALP (Spearman’s ρ=0.216; p=0.199, n=37) or P1NP (Spearman’s ρ=0.137; p=0.424, n=36) respectively and therefore further analysis on use of SUVpeak as a useful outcome measure was discontinued. FTV correlated positively with both serum biomarkers ALP (Spearman’s ρ=0.406; p=0.006, n=37) and P1NP (Spearman’s ρ=0.730; p<0.001, n=36). FAS strongly correlated with treatment-induced decrease in ALP (Spearman’s ρ=0.587; p=0.027) and P1NP (Spearman’s ρ=0.640; p=0.009). The baseline imaging (SUVpeak, FTV, TLF) and biochemical (ALP, P1NP) parameters did not correlate to disease response measured by either imaging (∆FTV) or serum biomarkers (∆ALP: ρ>-0.325, p>0.237 or ∆P1NP: ρ<0.489, p>0.064). Relative change in FTV (∆FTV) correlated positively with changes in ALP (∆ALP) (Spearman’s ρ=0.518; p=0.024) and changes in P1NP (∆P1NP) (Spearman’s ρ=0.489; p=0.032), (see Figure 5 and Table 4). FAS strongly correlated with ∆ALP (ρ=-0.568; p=0.027) and in ∆P1NP (ρ=-0.647; p=0.009). Individual responses In a substantial part of our patients, either ALP or P1NP (n=5) or both (n=3) failed to capture increased bone turnover as serum levels were below the upper limit of normal. In these patients, lesional pathological bone turnover was increased (median FTV 76cm3, IQR 61-289) and response to treatment could be adequately quantified (median ∆FTV -44%, IQR -67% to -19%) after either denosumab or non-denosumab and this was congruent with clinical findings (improvement of pain scores, reduced pain medication). The patients without elevated BTMs had relatively small baseline FTV (median 76cm3), in comparison to 467cm3 in patients with elevated BTMs. In one patient both Na[18F]F PET-CT quantitative parameters and P1NP were normal with solitary elevated ALP. In an other patient multiple quantitative Na[18F]F PET-CT follow-up studies were performed, a male FD patient (61-year-old when commencing denosumab) who was diagnosed with inflammatory bowel disease (IBD). This patient received treatment with bisphosphonates from 2014 to 2016 and adjusted dosage of 60mg trimonthly denosumab, because of the diagnosis of IBD in 2017. 8

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