Weighing the evidence for the roles of plasma versus local pyrophosphate in ectopic calcification disorders.

Ectopic calcification is characterized by inappropriate deposition of calcium mineral in non-skeletal connective tissues and can cause significant morbidity and mortality, particularly when it affects the cardiovascular system. Identification of the metabolic and genetic determinants of ectopic calcification could help distinguish individuals at greatest risk of developing these pathological calcifications and could guide development of medical interventions. Inorganic pyrophosphate (PP i ) has long been recognized as the most potent endogenous inhibitor of biomineralization. It has been intensively studied as both a marker and a potential therapeutic for ectopic calcification. Decreased extracellular concentrations of PP i have been proposed to be a unifying pathophysiological mechanism for disorders of ectopic calcification, both genetic and acquired. However, is reduced plasma concentrations of PP i a reliable predictor of ectopic calcification? This perspective article evaluates the literature in favor and against a pathophysiological role of plasma versus tissue PP i dysregulation as a determinant of, and as a biomarker for, ectopic calcification. This article is protected by copyright. All rights reserved.