Introduction Vitamin D and PTH play an important role in calcium homeostasis skin, liver, parathyroid gland, kidney, bone, and small intestine all play a role increased PTH and Vitamin D leads to increase serum calcium levels Vitamin D Physiology Overview Vitamin D and PTH play an important role in calcium homeostasis skin, liver, parathyroid gland, kidney, bone, and small intestine all play a role Increased PTH and Vitamin D leads to increase serum calcium levels Synthesis 7-Dehydrocholesterol precursor to calcitriol is stored in the skin where UV exposure converts it to previtamin D3. cholecalciferol (Vitamin D3) Previtamin D3 is then bound to vitamin-D binding protein (DBP) where it is carried to the liver and metabolized to 25-hydroxyvitamin D3 25-hydroxyvitamin D3 when calcium is low, parathyroid hormone (PTH) levels become elevated which activates 1-alpha-hydroxylase in the kidney 1-alpha-hydroxylase converts 25-hydroxyvitamin D to the active Vitamin D (calcitriol) laboratory study of choice to determine Vitamin D deficiency 1,25-dihydroxyvitamin D3 (Vitamin D, calcitriol) active form that controls calcium homeostasis in body by targeting intestines and bones (see function below) Function ↑ serum Ca2+ and phosphate via ↑ absorption of calcium and phosphate from the intestine ↑ bone resorption of Ca2+ and phosphate recall PTH functions to ↑ serum Ca2+ but ↓ serum phosphate Regulation PTH stimulates 1,25-(OH)2 vitamin D production hypocalcemia/hypophoshatemia stimulates 1,25-(OH)2 vitamin D production 1,25-(OH)2 vitamin D feedback negatively on itself Bone Healing Serves as an important regulator of the inflammatory response at the site of injury Promotes vasculogenesis and invasion into the wound healing bed by regulating VEGF and other growth factors Stimulates mesenchymal stem cell (MSC) commitment to osteoblastic lineage through adhesion to matrix proteins and the expression of integrins Stimulates the production of collagenous and non-collagenous extracellular matrix (ECM) proteins including collagen I, osteocalcin, and osteopontin PTH Physiology Synthesis secreted by the chief cells of parathyroid Function ↑ serum 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 which secretes IL-1 to activated osteoclasts ↑ kidney resorption of calcium in distal convoluted tubule ↓ kidney resorption of phosphate ↑ 1,25-(OH)2 vitamin D production Clinical Conditions Conditions related to PTH hypoparathyrodism pseudohypoparathyroidism renal osteodystrophy Conditions related to Vitamin D Rickets