Etidronate halts systemic arterial calcification in pseudoxanthoma elasticum

Abstract

A B S T R A C TBackground and aims: In pseudoxanthoma elasticum (PXE), low levels of inorganic pyrophosphate result in extensive arterial calcification. Recently, the treatment of ectopic mineralization in the PXE (TEMP) trial showed that one year of treatment with etidronate halts progression of femoral artery calcification in PXE patients. The aim of this study was to test the efficacy of etidronate on calcification in different vascular beds. Methods: In this prespecified post-hoc analysis of the TEMP trial, arterial calcification mass was quantified in the carotid siphon, common carotid artery, thoracic and abdominal aorta, coronary arteries, iliac arteries, and the femoropopliteal and crural arteries using CT at baseline and after one year of etidronate treatment or placebo. In addition, a total arterial calcification score was calculated. The difference in calcification progression was compared between the etidronate and placebo group. Results: 74 PXE patients were enrolled and randomized. Etidronate significantly halted progression of calcification in all vascular beds except for the coronary arteries. For the total arterial calcification score, the median absolute increase in mass score was −63.6 (−438.4-42.2) vs. 113.7 (9.4-377.1) (p < 0.01) and the median relative increase was −2.4% (−10.3-3.8) vs. 6.3% (0.2-15.8) (p < 0.01) in the etidronate and placebo arm, respectively. Conclusions: Etidronate treatment halts systemic arterial calcification in PXE. Further research must assess the long term safety and efficacy of etidronate on clinical outcomes in PXE.Abbreviations: ABCC6, ATP binding cassette subfamily C member 6; ACDC, arterial calcification due to a deficiency in CD73; CKD, chronic kidney disease; GACI, generalised arterial calcification of infancy; PPi, inorganic pyrophosphate; PXE, pseudoxanthoma elasticum

The effect of etidronate on choroidal neovascular activity in patients with pseudoxanthoma elasticum

“…Therefore, generalization of these findings to aminobisphosphonates is difficult. However, it is important to realize there is substantial evidence that etidronate can halt systemic calcification [7,26,27]. The inhibition of calcification might be another mechanism, independent of angiogenesis and inflammation, by which etidronate may be beneficial for ophthalmological disease in PXE.…”

Abdominal aortic calcification: from ancient friend to modern foe

“…65 In several genetic syndromes affecting the homeostasis of inorganic pyrophosphate, the old bisphosphonate etidronate was shown to inhibit and even reverse arterial calcifications in the abdominal aorta. 66,67 Although the newer bisphosphonates including alendronate 68 and ibandronate have shown no significant effect on arterial calcification in the abdominal aorta, 68,69 several small clinical trials have shown that etidronate does affect arterial calcification in more general populations as well. In patients on haemodialysis, etidronate was shown to inhibit and reverse progression of AAC 70 whereas it decreased abdominal aortic wall thickness on magnetic resonance imaging (MRI) in patients with hypercholesterolaemia.…”

Six months vitamin K treatment does not affect systemic arterial calcification or bone mineral density in diabetes mellitus 2

“…The findings in the femoral arteries were the primary outcome of the trial and were published elsewhere [28]. The calcification mass score was measured using an in-house developed program (iX Viewer, Image Science Institute, Utrecht, The Netherlands) as previously described [32,33] The observer manually identified potential calcifications that were segmented using a threshold of 130 Hounsfield Units (HU) for calcification. The calcification mass score was computed as the product of the volume of the lesion (in ml) and the mean attenuation (in HU) of the lesion.…”