Prevention of Arterial Calcium Deposition with Diphosphonates and Calcium Entry Blockers

Abstract

The arterial disease most commonly associated with an increase in arterial calcium is atherosclerosis. In the past, the deposition of calcium in atherosclerotic lesions has been considered to be an end-stage of advanced atheromata formation only [1]. While such end-stage calcification of plaques certainly is one of the prominent features of late atherosclerosis, it has long been recognized that discrete calcium mineral deposition may occur, especially on intimo-medial elastica, in otherwise normal-appearing arteries [2] and, therefore, may be considered an early event in atherogenesis. In fact, in recent years there has been mounting evidence that localized increases in arterial ionic calcium may play a key role in early atherogenesis, stimulating cellular functions of arterial smooth muscle cells and macrophages such as increased cell migration, mitosis, endocytosis of lipoproteins, as well as excessive synthesis and/or secretion of connective tissue macromolecules [3,4]. Focal increases in arterial calcium content also have been implicated in the early pathobiochemistry of the intercellular matrix molecules. Calcium ions are required for the complexing of low- density (LDL) and very-low-density lipoproteins (VLDL) to sulfated glycosaminoglycans. Calcium-dependent mechanisms may be responsible for the excessive degradation of arterial connective tissue such as the activation of elastolysis by macrophage elastase [5] or the release of collagenolytic, elastolytic, and mucolytic enzymes from platelets [6].