Pseudoxanthoma elasticum (PXE) is characterized by low levels of inorganic pyrophosphate (PPi) and a high activity of tissue-nonspecific alkaline phosphatase (TNAP). Lansoprazole is a partial inhibitor of TNAP. The aim was to investigate whether lansoprazole increases plasma PPi levels in subjects with PXE. We conducted a 2 × 2 randomized, double-blind, placebo-controlled crossover trial in patients with PXE. Patients were allocated 30 mg/day of lansoprazole or a placebo in two sequences of 8 weeks. The primary outcome was the differences in plasma PPi levels between the placebo and lansoprazole phases. 29 patients were included in the study. There were eight drop-outs due to the pandemic lockdown after the first visit and one due to gastric intolerance, so twenty patients completed the trial. A generalized linear mixed model was used to evaluate the effect of lansoprazole. Overall, lansoprazole increased plasma PPi levels from 0.34 ± 0.10 µM to 0.41 ± 0.16 µM (p = 0.0302), with no statistically significant changes in TNAP activity. There were no important adverse events. 30 mg/day of lansoprazole was able to significantly increase plasma PPi in patients with PXE; despite this, the study should be replicated with a large number of participants in a multicenter trial, with a clinical end point as the primary outcome.

Purpose: Coronary artery calcification (CAC) is utilized as an important tool for global risk assessment of cardiovascular events in individuals with intermediate risk. Ecto phosphodiesterase/nucleotide phosphohydrolase-1(ENPP1) converts extracellular nucleotides into inorganic pyrophosphate and it is a key regulator of tissue calcification that adjusts calcification in tissues like vascular smooth muscle cells. The main purpose of this clinical study was to find out the correlation between ENPP1 serum concentration and CAC in human for the first time. Methods: In this study 83 patients (16 diabetic patients and 67 non-diabetic patients) with coronary artery disease who fulfilled inclusion and exclusion criteria, entered the study. For all patients a questionnaire consisting demographic data and traditional cardiovascular risk factors were completed. Computed tomography (CT)-Angiography was carried out to determine coronary artery calcium score and enzyme-linked immunosorbent assay (ELISA) method was used for measuring ENPP1 serum concentrations. Results: There was a reverse significant correlation between ENPP1 serum concentration and total CAC score and also CAC of right coronary artery (RCA) (P<0.05) in non-diabetic patients. Conclusion: On the basis of our results, ENPP1 serum concentration may be a suitable biomarker for coronary artery disease at least in non-diabetic patients. However, more studies with higher sample size are necessary for its confirmation.