Cyclical Etidronate Reduces the Progression of Arterial Calcifications in Patients with Pseudoxanthoma Elasticum: A 6-Year Prospective Observational Study.

Pseudoxanthoma elasticum (PXE), a rare genetic disorder presenting with slowly progressing calcification of various tissues, including the arteries, is caused by mutations in the gene that lead to the reduction of pyrophosphate, a natural inhibitor of calcification. We showed that, compared to a placebo, the cyclical administration of etidronate, a stable pyrophosphate analog, significantly reduced arterial calcification assessed by low-dose CT scans after one year. The aim of the present prospective, single center, observational cohort study was the assessment of the efficacy and safety of cyclical etidronate in patients treated for periods longer than one year. Seventy-three patients were followed for a median of 3.6 years without etidronate and 2.8 years with etidronate, and each patient served as their own control. The median absolute yearly progression of total calcification volume during the period with etidronate (388 [83-838] µL) was significantly lower than that without etidronate (761 [362-1415] µL; < 0.001). The rates of the relative progression of arterial calcification were 11.7% (95% CI: 9.6-13.9) without etidronate compared to 5.3% (95% CI: 3.7-7.0) with etidronate, after adjustment for confounders. The cyclical administration of etidronate for nearly 3 years significantly reduced the progression rate of arterial calcification in patients with PXE with pre-existing calcifications without any serious adverse effects.