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Etidronate for Prevention of Ectopic Mineralization in Patients With Pseudoxanthoma Elasticum

Kranenburg, G., de Jong, P. A., Bartsta, JW., Lagerweij, SJ., Lam, M. G. E. H., Ossewaarde-Van Norel, J., Risseeuw, S., Van Leeuwen, R., Imhof, S. M., Verhaar, H., de Vries, JJ., Slart, R., Luurtsema, G., den Harder, A. M., Visseren, F. L. J., Mali, WP. & Spiering, W., 13-Mar-2018, In : Journal of the American College of Cardiology. 71, 10, p. 1117-1126 10 p.

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  • Etidronate for Prevention of Ectopic Mineralization

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DOI

  • G. Kranenburg
  • P.A. de Jong
  • JW Bartsta
  • SJ Lagerweij
  • Marnix G. E. H. Lam
  • Jeannette Ossewaarde-Van Norel
  • S Risseeuw
  • R Van Leeuwen
  • S.M. Imhof
  • H. Verhaar
  • JJ de Vries
  • Riemer Slart
  • Geert Luurtsema
  • Annemarie M den Harder
  • F. L. J. Visseren
  • WP Mali
  • Wilko Spiering

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 (18)fluoride 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 (<2.20mmol/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) (c) 2018 by the American College of Cardiology Foundation.

Original languageEnglish
Pages (from-to)1117-1126
Number of pages10
JournalJournal of the American College of Cardiology
Volume71
Issue number10
Publication statusPublished - 13-Mar-2018

    Keywords

  • arterial calcification, bisphosphonates, etidronate, PXE, GENERALIZED ARTERIAL CALCIFICATION, VASCULAR CALCIFICATION, CARDIOVASCULAR RISK, AORTIC CALCIFICATION, ABCC6 GENE, BISPHOSPHONATES, PYROPHOSPHATE, MUTATIONS, INFANCY, DISEASE

ID: 55382247