Phosphate as an adjunct to calcium in promoting coronary vascular calcification in chronic inflammatory states

Abstract

Bone releases calcium and phosphate in response to pro-inflammatory cytokine-mediated inflammation. The body develops impaired urinary excretion of phosphate with age and chronic inflammation given the reduction of the kidney protein Klotho, which is essential to phosphate excretion. Phosphate may also play a role in the development of the resistance of the parathyroid calcium-sensing receptor (CaSR) to circulating calcium thus contributing to calcium retention in the circulation. Phosphate can contribute to vascular smooth muscle dedifferentiation with manifestation of osteoblastogenesis and ultimately endovascular calcium phosphate precipitation. Thus phosphate, along with calcium, contributes to the calcification and inflammation of atherosclerotic plaques and the origin of these elements is likely the bone, which serves as storage for the majority of the body's supply of extracellular calcium and phosphate. Early cardiac evaluation of patients with chronic inflammation and attempts at up-regulating the parathyroid CaSR with calcimimetics or introducing earlier anti-resorptive treatment with bone active pharmacologic agents may serve to delay onset or reduce the quantity of atherosclerotic plaque calcification in these patients.

Keywords: atherosclerosis; bone; calcium; calcium-sensing receptor; inflammation; medicine; phosphate.

Figure 1.. This figure provides a schematic diagram of the differences in calcium handling in previously healthy children and adults following acute burn injury and the putative role of phosphate in adults and children.

Note that in children, pro-inflammatory cytokines up-regulate the parathyroid calcium-sensing receptor (CaSR) leading to hypocalcemic hypoparathyroidism and increased urinary calcium excretion, while in adults the up-regulation of the parathyroid CaSR response to pro-inflammatory cytokines is inhibited, possibly due to phosphate binding to the parathyroid CaSR leading to normo-or mildly hypercalcemic hyperparathyroidism and a reduction in urinary calcium excretion.