Statins and tissue mineralization: putative involvement of alkaline phosphatase

Many clinical trials have clearly demonstrated the benefit of statins in the prevention of coronary heart disease. Although other effects have subsequently been described, the so-called pleiotropic effects of statins, there is a tendency to relate all those effects, more or less directly, to inhibition of 3-hydroxy-3-methylglutaryl coenzyme A. Several clinical and laboratory studies show an association between statins and increased bone formation and/or density, but no clear explanation for that statin effect has emerged. We therefore hypothetized that statins may have an effect on alkaline phosphatase activity (ALP), an enzyme with an important role in bone mineralization and that may also contribute to pathological mineralization in other tissues, such as vascular calcification. Our experience with drug effects on ALP lead us to admit the possibility of finding a statin with an ALP increasing effect on bone but not on vascular tissue, or with a more marked effect upon one of the ALP isoforms or isoenzymes. That information would allow the design of clinical trials to confirm the suitability of a specific statin to a specific clinical condition.