Description

Calcitriol is the biologically active, hormonal form of vitamin D (1,25-dihydroxyvitaminD3​). It is the end-product of vitamin D metabolism in the body, primarily produced in the kidneys from calcidiol. Due to its potent and direct action, calcitriol is used as a medication to treat disorders of calcium metabolism, particularly in patients with impaired kidney function who are unable to produce it naturally. It is available in oral and intravenous formulations.

Indication

Calcitriol is indicated for the treatment of various conditions related to hypocalcemia (low blood calcium) and disturbed phosphate metabolism, particularly those where the body’s natural production of calcitriol is compromised. Its main indications include:

• Renal Osteodystrophy: This is a bone disease that occurs in patients with chronic kidney disease (CKD) who cannot produce adequate amounts of calcitriol.
• Hypoparathyroidism: It is used to manage both chronic and post-surgical hypoparathyroidism, a condition characterized by low levels of parathyroid hormone (PTH) and, consequently, low blood calcium.

• Hypocalcemia: It can be used to treat low blood calcium levels associated with various conditions, including patients on long-term dialysis.

Mechanism of Action

Calcitriol’s mechanism of action is based on its role as a hormone that regulates calcium and phosphate homeostasis throughout the body.

1. Hormonal Action: Unlike other forms of vitamin D that require activation, calcitriol is already in its final, active state. It acts by binding to the vitamin D receptor (VDR), which is found in cells in various organs, including the intestines, bones, and kidneys.
2. Regulation of Calcium and Phosphate: Upon binding to the VDR, calcitriol initiates a series of actions that increase the concentration of calcium and phosphate in the blood:

• • Intestinal Absorption: Its primary and most potent effect is to increase the absorption of dietary calcium and phosphate from the small intestine. It does this by stimulating the synthesis of calcium-binding proteins, such as calbindin-D, which facilitate the transport of these minerals across the intestinal wall.

• • Bone Metabolism: Calcitriol works in conjunction with parathyroid hormone (PTH) to stimulate the mobilization of calcium and phosphate from bone. This process, known as bone resorption, helps to raise blood mineral levels when dietary intake is insufficient.
  • Renal Reabsorption: Calcitriol acts on the kidneys to increase the reabsorption of calcium and phosphate from the urine, thus preventing their loss and helping to conserve these essential minerals.

3. Suppression of Parathyroid Hormone (PTH): In conditions like renal osteodystrophy, high levels of PTH contribute to bone disease. Calcitriol helps to normalize blood calcium levels, which in turn provides a feedback signal to the parathyroid glands to suppress the overproduction and secretion of PTH. This action is crucial for preventing bone damage.