Bone Homeostasis: Extracellular Calcium Levels and Their Control in Humans


Calcium (Ca2+) is an essential ion within the human body. It is extraordinary as an ion whose homeostasis is controlled and managed by many organs (bone, intestine, kidney, skin and thyroid). For a student, Ca2+ is a clear example of the complexities of biological control, integrating many systems. The understanding of the basic principles of control of this ion is a very sound foundation for consideration of other biological control mechanisms. The ion is responsible for the correct coordination of many functions (including excitable (muscle and nerve) and nonexcitable (endocrine in particular but also cellular enzymatic functions) tissue) and constitutes a large part of the inorganic component of the skeleton in the form of hydroxyapatite crystals. Calcium levels are kept within a narrow and specific range (7.5–11.5 mg/dL−1 in health; varying with age) and are regulated principally by three hormones – parathyroid hormone, calcitonin and cholecalciferol (vitamin D3). Other paracrine substances can also have a major effect. Excessive variations can lead to abnormalities of nerve function and porous bones (hypocalcaemia) or pathological calcification (hypercalcaemia).

Key Concepts

  • Ca2+ is a unique ion maintaining both the independent functional capacity of the organism being part of the rigid endoskeleton and having unique microlevel qualities controlling, very precisely, cell function.
  • Release and uptake of Ca2+ from the skeleton is undertaken by osteoblasts (bone depositing cells), osteoclasts (bone dissolving cells) and may have some influence from osteocytes (osteoblasts when surrounded by bones) and bone lining cells (thin cells possibly controlling ion exchange with bone).
  • Its characteristic role at cellular level can control ‘immediate’ cellular events such as exocytosis and contraction.
  • It is responsible for intercellular adherence.
  • It can influence chromosome functions.
  • It is integral to activation of enzyme systems.
  • As an ion whose serum levels are controlled closely, it demonstrates clearly basic principles of homeostasis that can serve as a foundation for understanding control of other ions/metabolites.
  • The control of serum Ca2+ demonstrates very clearly the interaction of several systems that are required to function correctly.
  • Ca2+ is a major coordinator of programmed cell death as well as a significant second messenger.

Keywords: bone; calcium; parathormone; calcitonin; vitamin D

Figure 1. Scanning electron photomicrograph of the surface of a bone illustrating an osteocyte lacuna. The surrounding bone has not completely formed and it is possible to see directly into the lacuna. The small canaliculi can be seen where the osteocyte processes may leave the lacuna and form a syncitium, possibly acting as load‐bearing sensors monitoring strain within the macroscopic bone (Mullender and Huiskes, ). Inset is a scanning electron photomicrograph of the edge of an osteoblast cell in culture. Processes can be seen extending from the cell surface and it can be deduced that this will occupy the lacunae. Copyright © Fraser McDonald.
Figure 2. Scanning electron photomicrograph showing scalloped areas that are indicative of a resorptive area. These areas are multiple Howships lacunae where the osteoclasts have resorbed bone substance. Within the picture are three large vessels and one smaller vessel (≈6–10 mm in diameter). These are the Volkmann canals travelling into the depths of the bony mass, carrying nutrients. Inset is a close up of the lumen of one of the larger vessels (another immature osteocyte lacunae is seen in the bottom of this figure). It shows the significant size of the vessels that are required to support the nutrition of the cells of bone. Copyright © Fraser McDonald.
Figure 3. General hormonal control of Ca2+ levels showing the main routes of increasing plasma Ca2+ levels and how the level of Ca2+ can be reduced by either bone formation or excretion.
Figure 4. A diagrammatic representation of a functional kidney nephron. Once within the plasma the Ca2+ is filtered within the kidney. The initial filtrate is produced at the Bowman's capsule after passing through the glomerulus; this is then passed to the proximal convoluted tubules. The filtrate is concentrated as it passes through the loop of Henle and final modifications to the solution are made in the distal convoluted tubules and the collecting ducts. The majority of Ca2+ is filtered at the Bowman's capsule, 60% is reabsorbed at the proximal convoluted tubules. The remainder is reabsorbed from the ascending limb of the loop of Henle and the distal convoluted tubules; PTH has to be present to allow this to occur.
Figure 5. Photomicrograph of human osteoblasts grown in cell culture stained for oestrogen receptors. No counterstain is present and both the nucleus and cytoplasm are clearly visible. Copyright © Fraser McDonald.
Figure 6. Diagrammatic representation of local factors and how they interact and control bone remodelling. A ‘+’ sign indicates stimulation of cell function or differentiation of progenitor cells and ‘−’ sign indicates a reduction in activity or differentiation.


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McDonald, Fraser(Jul 2015) Bone Homeostasis: Extracellular Calcium Levels and Their Control in Humans. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0002004.pub3]