TY - JOUR
T1 - Etidronate for Prevention of Ectopic Mineralization in Patients With Pseudoxanthoma Elasticum
AU - Kranenburg, Guido
AU - de Jong, Pim A.
AU - Bartstra, Jonas W.
AU - Lagerweij, Suzanne J.
AU - Lam, Marnix G.
AU - Ossewaarde-van Norel, Jeannette
AU - Risseeuw, Sara
AU - van Leeuwen, Redmer
AU - Imhof, Saskia M.
AU - Verhaar, Harald J.
AU - de Vries, Job J.
AU - Slart, Riemer H.J.A.
AU - Luurtsema, Gert
AU - den Harder, Annemarie M.
AU - Visseren, Frank L.J.
AU - Mali, Willem P.
AU - Spiering, Wilko
N1 - Funding Information:
This study was supported by the Dutch Innovation Fund of Health Insurers (Innovatiefonds Zorgverzekeraars), Dutch Foundation PXE Fund, Dutch Eye Association, and Foundation Friends of University Medical Center Utrecht. UNI-Pharma Kleon Tsetis Pharmaceutical Laboratories SA (Greece) provided all etidronate and placebo capsules for free, as manufacturer of the finished product (OSTOPOR hard capsules, 400 mg/capsule). UNI-Pharma SA was not involved in the design, the execution, the analysis, or the reporting of the Treatment of Ectopic Mineralization in Pseudoxanthoma Elasticum trial. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Publisher Copyright:
© 2018 American College of Cardiology Foundation
PY - 2018/3/13
Y1 - 2018/3/13
N2 - 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)
AB - 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)
KW - arterial calcification
KW - bisphosphonates
KW - etidronate
KW - PXE
UR - http://www.scopus.com/inward/record.url?scp=85042284956&partnerID=8YFLogxK
U2 - 10.1016/j.jacc.2017.12.062
DO - 10.1016/j.jacc.2017.12.062
M3 - Article
C2 - 29519353
AN - SCOPUS:85042284956
SN - 0735-1097
VL - 71
SP - 1117
EP - 1126
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 10
ER -