Dutch Heart Foundation (2009T038) and Dutch Diabetes Research Foundation (2012.11.1500).

BackgroundBrown adipose tissue (BAT) has emerged as a novel player in energy homeostasis in humans and is considered a potential new target for combating obesity and related diseases. The current ‘gold standard’ for quantification of BAT volume and activity is cold-induced 18F-FDG uptake in BAT. However, use of this technique is limited by cost and radiation exposure. Given the fact that BAT is a thermogenic tissue, mainly located in the supraclavicular region, the aim of the current study was to investigate whether cold-induced supraclavicular skin temperature and core body temperature may be alternative markers of BAT activation in humans.Subjects/MethodsBAT volume and activity were measured in 24 healthy lean adolescent males (mean age 24.1±0.8 years), using cold-induced 18F-FDG uptake with PET-CT. Core body temperature was measured continuously in the small intestine with use of an ingestible telemetric capsule and skin temperature was measured by eighteen wireless iButtons attached to the skin following ISO-defined locations.ResultsProximal and distal (hand/feet) skin temperatures markedly decreased upon cold exposure, while supraclavicular skin temperature significantly increased (35.2±0.1 vs. 35.5±0.1°C, p = 0.001). Furthermore, cold-induced supraclavicular skin temperature positively correlated with both total (R2 = 0.28, P = 0.010) and clavicular BAT volume (R2 = 0.20, P = 0.030) and clavicular SUVmax (R2 = 0.27, P = 0.010), while core body temperature did not.ConclusionsSupraclavicular skin temperature as measured by iButtons may have predictive value for BAT detection in adult humans. This is highly desirable considering the increasing interest in pharmacological interventions to stimulate BAT in human subjects.Trial Registration NTR 2473

Purpose To quantify Na 18 F-PET/CT uptake in relation to clinical and biochemical parameters of fibrous dysplasia (FD) severity and healthy bone (HB) metabolism. Secondary aims: comparing normalization for volume of distribution and determining reproducibility of Na 18 F-PET/CT uptake parameters in HB and FD. Relating Na 18 F uptake to skeletal burden score (SBS), bisphosphonate therapy and pain measured by Brief Pain Inventory (BPI). Methods In a prospective cohort study (n = 20), Na 18 F-PET/CT parameters of HB and FD were assessed by two independent readers to determine the cutoff defining increased bone uptake, optimized normalization, and interobserver agreement (ICC) and were related to SBS, serum biomarkers, medication, and clinical parameters. Results Physiological bone standardized uptake value (SUV) was best normalized but displayed large interpatient variation (total range 4.1-13.7 g/mL), with very high interobserver agreement (ICC = 0.964). FD burden defined by patient-specific SUV cutoffs reached near-perfect agreement for SUVpeak (ICC = 0.994) and total lesion fluorination (TLF) (ICC = 0.999). TLF correlated weakly with SBS (R 2 = 0.384, p = 0.047). TLF correlated positively with serum alkaline phosphatase (R 2 = 0.571, p = 0.004) and procollagen type 1 N-terminal propeptide (R 2 = 0.621, p = 0.002), SBS did not (p > 0.06). SBS and TLF both correlated with increased fibroblast growth factor-23 (R 2 = 0.596, p = 0.007 and R 2 = 0.541, p = 0.015, respectively). TLF was higher in use of bisphosphonates (p = 0.023), SBS was not. Average BPI scores correlated to increased FGF-23 (R 2 = 0.535, p = 0.045), workrelated BPI scores to higher SBS (R 2 = 0.518, p = 0.024), higher TLF (R 2 = 0.478, p = 0.036), and higher levels of FGF-23 (R 2 = 0.567, p = 0.034). Conclusions Individualized Na 18 F-PET/CT SUV cutoffs reproducibly discriminated HB from FD and were well-normalized. The strong relations of bone formation serum markers with Na 18 F-PET/CT FD burden measurements suggest clinical relevance over SBS as an adjunct instrument in FD patients. The correlation of both imaging modalities with increased work-related BPI scores also indicates clinical applicability. Moreover, SBS is known to remain stationary irrespective of use of medication, whereas TLF on Na 18 F-PET/CT was higher in baseline patients using bisphosphonates. This makes Na 18 F-PET/CT a promising tool to quantitatively measure treatment efficacy in FD. KeywordsSodium fluoride PET/CT . Fibrous dysplasia . Reproducibility . Serum biomarkers . Bisphosphonates This article is part of the Topical Collection on Orthopedics * Wouter van der Bruggen