Calcitriol is the biologically active form of vitamin D, a steroid hormone known for its influence on health beyond bone maintenance. Formally known as 1,25-dihydroxycholecalciferol or 1,25(OH)2D3, it is involved in various physiological processes throughout the body. Calcitriol contributes to mineral balance, immune responses, and cellular regulation.
Synthesis and Activation
Calcitriol synthesis begins with exposure to sunlight or dietary intake of vitamin D. In the skin, ultraviolet B (UVB) radiation converts 7-dehydrocholesterol into previtamin D3, which transforms into vitamin D3 (cholecalciferol). Vitamin D3 can also be obtained from foods like fatty fish, fortified dairy products, or supplements.
Vitamin D3 then undergoes a two-step activation process. The first step occurs in the liver, where the enzyme 25-hydroxylase converts vitamin D3 into 25-hydroxyvitamin D3, also known as calcifediol. Calcifediol then travels to the kidneys.
In the kidneys, a second hydroxylation takes place. Here, the enzyme 1-alpha-hydroxylase (CYP27B1) adds another hydroxyl group to calcifediol, yielding calcitriol. This enzymatic step is tightly controlled, with its activity stimulated by parathyroid hormone (PTH) and prolactin, and decreased by high levels of serum phosphate and FGF23.
How Calcitriol Works
Calcitriol exerts its effects by interacting with the vitamin D receptor (VDR), a protein found within the nuclei of cells across many tissues. When calcitriol binds to the VDR, it changes the VDR’s shape. This altered VDR then pairs with the retinoid X receptor (RXR), forming a VDR-RXR complex.
This VDR-RXR complex moves into the cell’s nucleus and attaches to specific DNA sequences known as vitamin D response elements (VDREs). These VDREs are located in the promoter regions of target genes, which control gene activity. By binding to these elements, the calcitriol-VDR-RXR complex can either increase or decrease the expression of various genes.
This gene regulation allows calcitriol to influence a wide array of cellular processes. For instance, in the intestines, calcitriol upregulates the expression of proteins like calbindin and various calcium channels, which absorb dietary calcium and phosphate. This demonstrates how calcitriol orchestrates its diverse biological functions.
Broader Physiological Functions
Calcitriol’s most recognized function involves regulating calcium and phosphorus levels, which is fundamental for strong bones and teeth. It enhances the absorption of dietary calcium and phosphate from the gastrointestinal tract, ensuring these minerals are available in the bloodstream. Calcitriol also promotes the reabsorption of calcium in the kidneys, limiting its loss in urine.
Beyond mineral balance, calcitriol plays a role in bone remodeling. It influences osteoblasts, which are bone-building cells, to release a signaling molecule called RANKL. This molecule activates osteoclasts, cells responsible for breaking down bone tissue and releasing calcium into the blood. This coordinated action helps maintain bone density and strength.
Calcitriol also modulates the immune system. Vitamin D receptors are present in various immune cells, including monocytes, macrophages, dendritic cells, and activated T and B cells. Calcitriol enhances innate immune responses and helps regulate adaptive immunity, contributing to the body’s defense against infections and mitigating excessive inflammation.
Calcitriol has implications for cardiovascular health and cell growth. It influences cell proliferation and differentiation, processes involved in the growth and specialization of cells. These actions suggest broader roles for calcitriol in maintaining tissue health and potentially preventing certain chronic conditions.
Medical Applications and Management
As a medication, calcitriol is prescribed to address conditions related to calcium and phosphorus imbalances. It is commonly used to treat hypocalcemia, a condition characterized by low blood calcium levels, particularly in individuals with chronic kidney disease or hypoparathyroidism. In kidney disease, the kidneys may be unable to convert vitamin D into its active form, necessitating calcitriol supplementation.
Calcitriol also helps manage secondary hyperparathyroidism, a condition often seen in chronic kidney disease where parathyroid glands become overactive in an attempt to raise calcium levels. By increasing calcium absorption, calcitriol can help suppress excessive parathyroid hormone secretion. It is also used in managing metabolic bone disease, including osteomalacia and osteoporosis, by promoting proper bone mineralization.
Administering calcitriol requires careful monitoring by healthcare professionals. Dosage must be individualized, typically starting with a low dose such as 0.25 micrograms daily, and adjusted based on regular measurements of serum calcium, phosphorus, and parathyroid hormone levels. Too much calcitriol can lead to hypercalcemia, a condition of high blood calcium, which can cause symptoms like nausea, vomiting, increased thirst, and muscle weakness.
Patients are often monitored twice weekly during initial dosage adjustments and at least monthly after stabilization. Concurrent use of calcium supplements or other vitamin D analogs may increase the risk of hypercalcemia, so these need careful management. Adhering to prescribed dosages and dietary recommendations, such as a low-calcium diet if hypercalcemia occurs, is important for safe and effective treatment.