Whole-Body Visualization of Ectopic Bone Formation of Arteries and Skin in Pseudoxanthoma Elasticum

Oudkerk, Sytse F.; Jong, Pim A. de; Blomberg, Björn Alexander; Scholtens, Asbjørn M.; Mali, Willem P.Th.M.; Spiering, Wilko

doi:10.1016/j.jcmg.2015.06.006

Cited by 10 publications

(9 citation statements)

References 2 publications

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“…These results are consistent with those recently published where patients with higher skin Phenodex scores exhibited higher 18F-NaF uptake in the neck [32]. In the vascular system 18F-NaF uptake was observed exclusively in the aorta and the femoral arteries, substantiating our previous characterization of vulnerability to PXE damage in these regions [1,23,33]. Similarly, MVC and non-calcified atherosclerotic lesions constitute a predominant leg artery calcification type in the general population.…”

Section: Pxe As a Prime Example Of Chronic Skin And Arterial Calcificationsupporting

confidence: 92%

“…This observation did however lead us to hypothesize about the kinetics of ectopic calcification. As 18F-NaF activity increases [33], PPi rates decrease [4,5]. Nevertheless, it is possible that the decrease in PPi plasma levels alone does not account for ectopic calcification [36].…”

Section: Pxe As a Prime Example Of Chronic Skin And Arterial Calcificationmentioning

confidence: 99%

“…18F-NaF-PET-CT is able to identify calcification that cannot be detected by CT-resolution alone [50]. It is recognized as a reliable detector for quantifying ectopic calcification [33] and tracking its progression [50].…”

Section: F-naf As a Diagnostic And Follow-up Biomarker In Pxementioning

confidence: 99%

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Assessment of Inflammation and Calcification in Pseudoxanthoma Elasticum Arteries and Skin with 18F-FluroDeoxyGlucose and 18F-Sodium Fluoride Positron Emission Tomography/Computed Tomography Imaging: The GOCAPXE Trial

Omarjee

Mention

Janin

et al. 2020

JCM

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Background: Pseudoxanthoma elasticum (PXE) is an inherited metabolic disease characterized by elastic fiber fragmentation and ectopic calcification. There is growing evidence that vascular calcification is associated with inflammatory status and is enhanced by inflammatory cytokines. Since PXE has never been considered as an inflammatory condition, no incidence of chronic inflammation leading to calcification in PXE has been reported and should be investigated. In atherosclerosis and aortic stenosis, positron emission tomography combined with computed tomographic (PET-CT) imaging has demonstrated a correlation between inflammation and calcification. The purpose of this study was to assess skin/artery inflammation and calcification in PXE patients. Methods: 18F-FluroDeoxyGlucose (18F-FDG) and 18F-Sodium Fluoride (18F-NaF) PET-CT, CT-imaging and Pulse wave velocity (PWV) were used to determine skin/vascular inflammation, tissue calcification, arterial calcium score (CS) and stiffness, respectively. In addition, inorganic pyrophosphate, high-sensitive C-reactive protein and cytokines plasma levels were monitored. Results: In 23 PXE patients, assessment of inflammation revealed significant 18F-FDG uptake in diseased skin areas contrary to normal regions, and exclusively in the proximal aorta contrary to the popliteal arteries. There was no correlation between 18F-FDG uptake and PWV in the aortic wall. Assessment of calcification demonstrated significant 18F-NaF uptake in diseased skin regions and in the proximal aorta and femoral arteries. 18F-NaF wall uptake correlated with CS in the femoral arteries, and aortic wall PWV. Multivariate analysis indicated that aortic wall 18F-NaF uptake is associated with diastolic blood pressure. There was no significant correlation between 18F-FDG and 18F-NaF uptake in any of the artery walls. Conclusion: In the present cross-sectional study, inflammation and calcification were not correlated. PXE would appear to more closely resemble a chronic disease model of ectopic calcification than an inflammatory condition. To assess early ectopic calcification in PXE patients, 18F-NaF-PET-CT may be more relevant than CT imaging. It potentially constitutes a biomarker for disease-modifying anti-calcifying drug assessment in PXE.

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Section: Pxe As a Prime Example Of Chronic Skin And Arterial Calcificationsupporting

confidence: 92%

Section: Pxe As a Prime Example Of Chronic Skin And Arterial Calcificationmentioning

confidence: 99%

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Assessment of Inflammation and Calcification in Pseudoxanthoma Elasticum Arteries and Skin with 18F-FluroDeoxyGlucose and 18F-Sodium Fluoride Positron Emission Tomography/Computed Tomography Imaging: The GOCAPXE Trial

Omarjee

Mention

Janin

et al. 2020

JCM

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“…However, these trials did not yield positive conclusions and it is possible that the quantification methodology combined with the heterogeneity of the manifestations may have contributed to the inconclusive results. The capacity of 18 F-sodium fluoride ( 18 F-NaF) positron emission tomography/computed tomography (PET/CT) to identify and evaluate metabolically active osteogenesis in skin and arteries in PXE patients has been demonstrated [159,160]. This method was applied in the recent TEMP clinical trial and was able to discern some phenotypical changes within a year following etidronate administration (Cf.…”

Section: Treatment Outcome Conundrummentioning

confidence: 99%

ABCC6, Pyrophosphate and Ectopic Calcification: Therapeutic Solutions

Shimada

Pomozi

Zoll

et al. 2021

IJMS

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Pathological (ectopic) mineralization of soft tissues occurs during aging, in several common conditions such as diabetes, hypercholesterolemia, and renal failure and in certain genetic disorders. Pseudoxanthoma elasticum (PXE), a multi-organ disease affecting dermal, ocular, and cardiovascular tissues, is a model for ectopic mineralization disorders. ABCC6 dysfunction is the primary cause of PXE, but also some cases of generalized arterial calcification of infancy (GACI). ABCC6 deficiency in mice underlies an inducible dystrophic cardiac calcification phenotype (DCC). These calcification diseases are part of a spectrum of mineralization disorders that also includes Calcification of Joints and Arteries (CALJA). Since the identification of ABCC6 as the “PXE gene” and the development of several animal models (mice, rat, and zebrafish), there has been significant progress in our understanding of the molecular genetics, the clinical phenotypes, and pathogenesis of these diseases, which share similarities with more common conditions with abnormal calcification. ABCC6 facilitates the cellular efflux of ATP, which is rapidly converted into inorganic pyrophosphate (PPi) and adenosine by the ectonucleotidases NPP1 and CD73 (NT5E). PPi is a potent endogenous inhibitor of calcification, whereas adenosine indirectly contributes to calcification inhibition by suppressing the synthesis of tissue non-specific alkaline phosphatase (TNAP). At present, therapies only exist to alleviate symptoms for both PXE and GACI; however, extensive studies have resulted in several novel approaches to treating PXE and GACI. This review seeks to summarize the role of ABCC6 in ectopic calcification in PXE and other calcification disorders, and discuss therapeutic strategies targeting various proteins in the pathway (ABCC6, NPP1, and TNAP) and direct inhibition of calcification via supplementation by various compounds.

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“…Furthermore, 18 F‐NaF PET‐CT identifies high‐risk coronary and carotid plaques as well as progressive abdominal aortic aneurysm . The technique even has the power to image other types of ectopic calcifications in whole‐body scans, such as skin calcifications . Hence, it may lend itself as marker of nascent calcification, and will prove highly valuable in assessing VC inhibitors, in both clinical and preclinical settings …”

Section: Vascular Calcificationmentioning

confidence: 99%

Investigational Pharmacological Treatments for Vascular Calcification

Schantl

Ivarsson²,

Leroux

2018

Advanced Therapeutics

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In the past decade, significant progress has been made in understanding the medical threats posed by vascular calcification (VC). This recent development comes after a long history of misinterpreting this condition as a mere consequence of aging. As a result, there is presently no pharmacological treatment approved for the prevention or ablation of VC. Patients diagnosed with this chronic and debilitating condition are hence left at a great risk of experiencing serious cardiovascular events. Researchers, however, are ever better understanding the disease's pathophysiology, and promising avenues for drug development have emerged. In this review, recent clinical results of proposed calcification inhibitors are consolidated and selected investigational therapeutics are portrayed. Finally, opportunities for drug development approaches are highlighted and an objective account of challenges that remain in achieving this goal is provided.

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Whole-Body Visualization of Ectopic Bone Formation of Arteries and Skin in Pseudoxanthoma Elasticum

Cited by 10 publications

References 2 publications

Assessment of Inflammation and Calcification in Pseudoxanthoma Elasticum Arteries and Skin with 18F-FluroDeoxyGlucose and 18F-Sodium Fluoride Positron Emission Tomography/Computed Tomography Imaging: The GOCAPXE Trial

Assessment of Inflammation and Calcification in Pseudoxanthoma Elasticum Arteries and Skin with 18F-FluroDeoxyGlucose and 18F-Sodium Fluoride Positron Emission Tomography/Computed Tomography Imaging: The GOCAPXE Trial

ABCC6, Pyrophosphate and Ectopic Calcification: Therapeutic Solutions

Investigational Pharmacological Treatments for Vascular Calcification

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