Introduction Calcium homeostasis controlled by a combination of vitamin D and PTH Vitamin D alone PTH Pathway Synthesis PTH Pathway secreted by the chief cells of parathyroid responds to ionized calcium levels (physiologically-active), not total calcium levels (which includes physiologically-inactive calcium bound to protein) in low pH settings, an excess of hydrogen ions bind to protein, displacing calcium ions leading to an increase in ionized calcium and vice versa in high pH settings Function ↑ serum free Ca2+ and ↓ serum phosphate in response to hypocalcemia/hypomagnesemia via ↑ bone resorption of calcium and phosphate (bone is destroyed) PTH receptor is on the osteoblasts secretes IL-1 to activate osteoclasts via production of M-CSF and RANK-L PTH decreases osteoprotegrin (OPG), decoy receptor for RANKL, thereby resulting in an increased interaction between RANKL and osteoclasts ↑ kidney resorption of calcium in distal convoluted tubule ↓ kidney resorption of phosphate (increasing urine phosphate) ↑ 1,25-(OH)2 vitamin D production (via 1 alpha-hydroxylase) Clinical Conditions Hypoparathyroidism Hyperparathyroidism Familial hypocalciuric hypercalcemia defective calcium receptor that can not detect elevated calcium level loss of negative feedback causes hypercalcemia (via increased PTH, 1-alpha OH)