Ca2+ as an extracellular signal in bone

Cell Calcium. 2004 Mar;35(3):249-55. doi: 10.1016/j.ceca.2003.10.014.


Bone is the major sink and store for calcium and it fulfils essential roles in the maintenance of extracellular free ionised calcium concentration ([Ca2+]e) within its homeostatic range (1.1-1.3 mM). In response to acute hypercalcaemia or hypocalcaemia, Ca2+ is rapidly transported into or out of bone. Bone turnover (and therefore bone Ca2+ turnover) achieves the long-term correction of the [Ca2+]e by the metabolic actions of osteoblasts and osteoclasts, as they respectively incorporate or release Ca2+ from bone. These processes are regulated by the actions of hormones, such as parathyroid hormone (PTH), the release of which is a function of the [Ca2+]e, and is regulated by the action of the Ca2+-sensing receptor (CaR) in the parathyroid gland. Tissue culture studies indicate that bone cells also directly respond to increasing and decreasing [Ca2+]e in their vicinity, independently of the systemic factors. Nevertheless, further studies are necessary to identify how the acute and long-term local changes in [Ca2+]e affect bone cells and the physiological processes they are involved in. Also, the molecular mechanisms which enable the bone cells to sense and respond to [Ca2+]e are not clear. Like the parathyroid cells, bone cells also express the CaR, and accumulating evidence indicates the involvement of this receptor in their responses to the changing extracellular ionic environment.

Publication types

  • Review

MeSH terms

  • Animals
  • Bone Remodeling / physiology
  • Bone Resorption / metabolism
  • Bone and Bones / physiology*
  • Calcium / metabolism*
  • Extracellular Space / metabolism
  • Homeostasis / physiology
  • Humans
  • Hyperparathyroidism / drug therapy
  • Ion Channels / physiology
  • Osteoblasts / physiology
  • Osteoclasts / physiology
  • Osteocytes / physiology
  • Osteoporosis / drug therapy
  • Receptors, Calcium-Sensing / agonists
  • Receptors, Calcium-Sensing / antagonists & inhibitors
  • Receptors, Calcium-Sensing / physiology*


  • Ion Channels
  • Receptors, Calcium-Sensing
  • Calcium