Physiology of the Calcium-Parathyroid Hormone-Vitamin D Axis

Front Horm Res. 2018:50:1-13. doi: 10.1159/000486060. Epub 2018 Mar 29.


Classic endocrine feedback loops ensure the regulation of blood calcium. Calcium in the extracellular fluid (ECF) binds and activates the calcium sensing receptor (CaSR) on the parathyroid cells, leading to an increase in intracellular calcium. This in turn leads to a reduced parathyroid hormone (PTH) release. Hypocalcemia leads to the opposite sequence of events, namely, lowered intracellular calcium and increased PTH production and secretion. PTH rapidly increases renal calcium reabsorption and, over hours to days, enhances osteoclastic bone resorption and liberates both calcium and phosphate from the skeleton. PTH also increases fibroblast growth factor 23 (FGF23) release from mature osteoblasts and osteocytes. PTH stimulates the renal conversion of 25-hydroxyvitamin D (25[OH]D) to 1,25(OH)2D, likely over several hours, which in turn will augment intestinal calcium absorption. Prolonged hypocalcemia and exposure to elevated PTH may also result in 1,25(OH)2D-mediated calcium and phosphorus release from bone. These effects restore the ECF calcium to normal and inhibit further production of PTH and 1,25(OH)2D. Additionally, FGF23 can be released from bone by 1,25(OH)2D and can in turn reduce 1,25(OH)2D concentrations. FGF23 has also been reported to decrease PTH production. When ECF calcium is in the hypercalcemic range, PTH secretion is reduced and renal 1,25(OH)2D production is decreased. In addition, the elevated calcium per se stimulates the renal CaSR, thus inducing calciuria. Therefore, suppression of PTH release and 1,25(OH)2D synthesis and stimulation of the renal CaSR lead to reduced renal calcium reabsorption, decreased skeletal calcium release, and decreased intestinal calcium absorption, resulting in the normalization of the elevated ECF calcium.

Publication types

  • Review

MeSH terms

  • Calcium / metabolism*
  • Fibroblast Growth Factor-23
  • Homeostasis / physiology*
  • Humans
  • Parathyroid Hormone / metabolism*
  • Vitamin D / analogs & derivatives*
  • Vitamin D / metabolism


  • FGF23 protein, human
  • Parathyroid Hormone
  • Vitamin D
  • Fibroblast Growth Factor-23
  • 25-hydroxyvitamin D
  • Calcium