Would acetazolamide inhibit progression of atheromatous vascular calcification?

Vascular calcification is a recognised source of morbidity among mid-age and elderly subjects. Its development follows classical mineralisation pathways, inhibited by acidosis. It is known that the final mechanism of tissue mineralization involves three processes, all of which are highly pH dependent. Calcium interacts with phosphate in its trivalent form, but this step is inhibited by pyrophosphate, itself a source of phosphate when hydrolysed by alkaline phosphatase. Separately, matrix vesicles create nucleation sites and may indirectly disrupt vascular smooth muscle cells. Metabolic acidosis acts at every point to delay mineralization. The diuretic acetazolamide creates a sustained mild acidosis with some phosphate loss and, though usually ineffective in the experimental model, has been used with success in certain clinical conditions. We suggest that acetazolamide, well studied and tolerated, might inhibit progression of vascular calcification in subjects at risk through its dual action of lowering tissue pH and local phosphate concentration.