Guido Kranenburg1, Pim A de Jong2, Jonas W Bartstra1, Suzanne J Lagerweij2, Marnix G Lam2, Jeannette Ossewaarde-van Norel3, Sara Risseeuw3, Redmer van Leeuwen3, Saskia M Imhof3, Harald J Verhaar4, Job J de Vries2, Riemer H J A Slart5, Gert Luurtsema5, Annemarie M den Harder2, Frank L J Visseren1, Willem P Mali2, Wilko Spiering6. 1. Department of Vascular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. 2. Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. 3. Department of Ophthalmology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. 4. Department of Geriatric Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. 5. Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. 6. Department of Vascular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. Electronic address: W.Spiering@umcutrecht.nl.
Abstract
BACKGROUND: In pseudoxanthoma elasticum (PXE), low pyrophosphate levels may cause ectopic mineralization, leading to skin changes, visual impairment, and peripheral arterial disease. OBJECTIVES: The authors hypothesized that etidronate, a pyrophosphate analog, might reduce ectopic mineralization in PXE. METHODS: In the Treatment of Ectopic Mineralization in Pseudoxanthoma Elasticum trial, adults with PXE and leg arterial calcifications (n = 74) were randomly assigned to etidronate or placebo (cyclical 20 mg/kg for 2 weeks every 12 weeks). The primary outcome was ectopic mineralization, quantified with 18fluoride positron emission tomography scans as femoral arterial wall target-to-background ratios (TBRfemoral). Secondary outcomes were computed tomography arterial calcification and ophthalmological changes. Safety outcomes were bone density, serum calcium, and phosphate. RESULTS: During 12 months of follow-up, the TBRfemoral increased 6% (interquartile range [IQR]: -12% to 25%) in the etidronate group and 7% (IQR: -9% to 32%) in the placebo group (p = 0.465). Arterial calcification decreased 4% (IQR: -11% to 7%) in the etidronate group and increased 8% (IQR: -1% to 20%) in the placebo group (p = 0.001). Etidronate treatment was associated with significantly fewer subretinal neovascularization events (1 vs. 9, p = 0.007). Bone density decreased 4% ± 12% in the etidronate group and 6% ± 9% in the placebo group (p = 0.374). Hypocalcemia (<2.20 mmol/l) occurred in 3 versus 1 patient (8.1% vs. 2.7%, p = 0.304). Eighteen patients (48.6%) treated with etidronate, compared with 0 patients treated with placebo (p < 0.001), experienced hyperphosphatemia (>1.5 mmol/l) and recovered spontaneously. CONCLUSIONS: In patients with PXE, etidronate reduced arterial calcification and subretinal neovascularization events but did not lower femoral 18fluoride sodium positron emission tomography activity compared with placebo, without important safety issues. (Treatment of Ectopic Mineralization in Pseudoxanthoma elasticum; NTR5180).
RCT Entities:
BACKGROUND: In pseudoxanthoma elasticum (PXE), low pyrophosphate levels may cause ectopic mineralization, leading to skin changes, visual impairment, and peripheral arterial disease. OBJECTIVES: The authors hypothesized that etidronate, a pyrophosphate analog, might reduce ectopic mineralization in PXE. METHODS: In the Treatment of Ectopic Mineralization in Pseudoxanthoma Elasticum trial, adults with PXE and leg arterial calcifications (n = 74) were randomly assigned to etidronate or placebo (cyclical 20 mg/kg for 2 weeks every 12 weeks). The primary outcome was ectopic mineralization, quantified with 18fluoride positron emission tomography scans as femoral arterial wall target-to-background ratios (TBRfemoral). Secondary outcomes were computed tomography arterial calcification and ophthalmological changes. Safety outcomes were bone density, serum calcium, and phosphate. RESULTS: During 12 months of follow-up, the TBRfemoral increased 6% (interquartile range [IQR]: -12% to 25%) in the etidronate group and 7% (IQR: -9% to 32%) in the placebo group (p = 0.465). Arterial calcification decreased 4% (IQR: -11% to 7%) in the etidronate group and increased 8% (IQR: -1% to 20%) in the placebo group (p = 0.001). Etidronate treatment was associated with significantly fewer subretinal neovascularization events (1 vs. 9, p = 0.007). Bone density decreased 4% ± 12% in the etidronate group and 6% ± 9% in the placebo group (p = 0.374). Hypocalcemia (<2.20 mmol/l) occurred in 3 versus 1 patient (8.1% vs. 2.7%, p = 0.304). Eighteen patients (48.6%) treated with etidronate, compared with 0 patients treated with placebo (p < 0.001), experienced hyperphosphatemia (>1.5 mmol/l) and recovered spontaneously. CONCLUSIONS: In patients with PXE, etidronate reduced arterial calcification and subretinal neovascularization events but did not lower femoral 18fluoride sodium positron emission tomography activity compared with placebo, without important safety issues. (Treatment of Ectopic Mineralization in Pseudoxanthoma elasticum; NTR5180).
Authors: Sytse F Oudkerk; Firdaus A A Mohamed Hoesein; Willem PThM Mali; F Cumhur Öner; Jorrit-Jan Verlaan; Pim A de Jong; Gregory L Kinney; John Hokanson; David Lynch; Edwin K Silverman; Matthew J Budoff; Elizabeth A Regan Journal: Atherosclerosis Date: 2019-05-30 Impact factor: 5.162
Authors: Melissa E M Peters; Esther J M de Brouwer; Jonas W Bartstra; Willem P Th M Mali; Huiberdina L Koek; Annemieke J M Rozemuller; Annette F Baas; Pim A de Jong Journal: Neurol Clin Pract Date: 2020-10