• D3 (cholecalciferol) from exposure of skin (stratum basale) to sun, ingestion of fish, milk, plants.
• D2 (ergocalciferol) from ingestion of plants, fungi, yeasts.
• Both converted to 25-OH D3 (storage form) in liver and to the active form 1,25-(OH)2 D3 (calcitriol) in kidney.
• Function
  • ↑ intestinal absorption of Ca2+ and PO43.
  • ↑ bone mineralization at low levels (mediated by osteoblast release of osteocalcin (calcium binder) and phosphatases that promote bone mineralization.
  • ↑ bone resorption at higher levels.
• Regulation
  • ↑ PTH, ↓ Ca2+, ↓ PO43- → 1,25-(OH)2D3 production.
  • 1,25-(OH)2D3  feedback inhibits its own production.
  • ↑ PTH→ ↑Ca2+ reabsorption and  ↓ PO43- reabsorption in the kidney.
• Deficiency
  • Rickets in children (deformity, such as genu varum “bow legs”[A]), osteomalacia in adults (bone pain and muscle weakness), hypocalcemic tetany.
  • Caused by malabsorption, ↓ sun exposure, poor diet, chronic kidney disease.
  • Give oral vitamin D to breastfed infants.
  • Deficiency is exacerbated by pigmented skin, premature birth.
• Excess
  • Hypercalcemia, hypercalciuria, loss of appetite, stupor. Seen in granulomatous disease (↑ activation of vitamin D by epithelioid macrophages).