Calcium homeostasis

Question 1

What is calcium homeostasis?

Answer 1

Calcium homeostasis refers to the maintenance of a constant concentration of calcium ions in the extracellular fluid.

Question 2

What is the role of vitamin d in calcium homeostasis?

Answer 2

Vitamin D plays an important role in calcium homeostasis and bone metabolism, with the capacity to modulate innate and adaptive immune function, cardiovascular function, and proliferation and differentiation of both normal and malignant keratinocytes.

Question 3

What are osteoblasts?

Answer 3

Osteoblasts are specialized mesenchymal cells that synthesize bone matrix and coordinate the mineralization of the skeleton.

These cells work in harmony with osteoclasts, which resorb bone, in a continuous cycle that occurs throughout life.

Question 4

What are osteoclasts?

Answer 4

Osteoclasts are the cells that degrade bone to initiate normal bone remodeling and mediate bone loss in pathologic conditions by increasing their resorptive activity.

They are derived from precursors in the myeloid/ monocyte lineage that circulate in the blood after their formation in the bone marrow.

Question 5

What is parathyroid hormone?

Answer 5

A peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine.

Question 6

What is calcitriol?

Answer 6

Calcitriol is the active form of vitamin D, normally made in the kidney. It is a hormone which binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the expression of many genes.

Question 7

What are the different roles of calcium?

Answer 7

Neuromuscular excitability, myocontraction​.
Nerve transmission.​
Coagulation of blood or milk.​
As a second messenger to initiate biological process.
Essential for various enzymatic activity.
Modulates viscosity in the intracellular medium.
Essential for the process of exocytosis.​
Cell-cell interaction, cell duplication.
Involved in the process of apoptosis.​
Essential element of bones, teeth, cartilage.

Question 8

What is osteogenesis?

Answer 8

The development and formation of bone.

​Osteoblasts surrounded by the bone matrix, decreased their activity and are converted into osteocytes. They remain connected with the exterior via small fluid-containing channels (canaliculi).

Mineralisation: calcium phosphate cristals (hydroxyapatite) deposit on the organic matrix.

Osteoblasts secrete also IGF, which will remain trapped in the bone matrix, along with many other important cytokines (bone morphogenic proteins).​

Question 9

What is osteolysis?

Answer 9

Osteolysis is a progressive condition where bone tissue is destroyed. In this process, bones lose minerals (mostly calcium), softens, degenerates and become weaker.

Recruitment of the osteoclasts by cytokines (IL6) secreted by osteoblasts. Adhesion to the bone matrix and proteolysis of collagen.​

Release of the cytokine IGF (trapped in the bone matrix) which activates osteoblasts.​

Question 10

What is the role of calcium in the intestines?

Answer 10

Activates transcription of calcium binding protein (calbindin) cytoplasmic protein that carry Ca2+ ions from the lumen side (brush border) to the capillary side of the intestinal cells.

Question 11

What is the role of calcium in the bones?

Answer 11

Critical for bone mineralization, some effects still not understood, stimulates the transcription of fibrinonectin, osteonectin and osteocalcin but suppress synthesis of collagen, also promotes the maturation of osteoclasts.

Question 12

What is the role of calcium in the kidneys?

Answer 12

Increases Ca2+ reabsorption from the kidney tubules (less potent effect) and inhibit Ca2+ secretion.

Question 13

What is the role of calcium in immune cells?

Answer 13

Complex effects, decrease production of some inflammatory substances. ​

Question 14

What is the role of calcium in various tissues?

Answer 14

Regulation of intracellular calcium and in the control of cell differentiation and growth.

Question 15

What does parathyroid hormone do in the bones?

Answer 15

Stimulates the release of calcium in an indirect process through osteoclasts which ultimately lead to resorption of the bones.

Elevates plasma Ca2+ levels by stimulating bone resorption. Activates osteoclasts (increase in size and shape-change, resorption zone in which they will adhere on the matrix increases), increase in protease activity, promoting the formation of cavities.​

However, osteoclasts, but not osteoblasts, lack of PTH receptors. PTH likely acts on osteoblasts by inducing the release of an unidentified paracrine agent which stimulates the osteoclasts directly. ​

Question 16

What does parathyroid hormone do in the kidneys?

Answer 16

Increases reabsorption of Ca2+ from distal tubule.

Likely, via (cAMP-dep) activation of a Ca2+ carrier located at the lumen side of the cells.

Inhibit reabsorption of phosphate in the proximal tubule. Stimulates calcitriol synthesis.​

Question 17

What is calcitonin?

Answer 17

It acts to reduce blood calcium, opposing the effects of parathyroid hormone.

Decreases Ca2+ levels by directly inhibiting osteoclast activity.

Question 18

What role do oestrogens/androgens play​?

Answer 18

Crucial role, oppose bone resorbing, inhibit osteoclast recruitement and cause osteoclasts apoptosis.​

Question 19

What is the role of glucocorticoids?

Answer 19

Low doses required for osteoblast differentiation.

Excessive concentrations inhibit bone formation by inhibiting osteoblast differentiation and activity, also decreases intestinal absorption of Ca2+ and phosphate.

Question 20

What is osteoporosis?

Answer 20

Osteoporosis causes bones to become weak and brittle - so brittle that a fall or even mild stresses such as bending over or coughing can cause a fracture.

Question 21

What is the treatment for osteoporosis?

Answer 21

In the elderly:

Biphosphanate, non-metabolisable analogue of pyrophosphate (alendronate, etidronate), reduces turnover of bone, accumulate at sites of bone mineralisation.​

​In post menopausal women: ​

HRT, estrogens (tamoxifen) plus biphosphanate, and calcium salts, sometimes calcitonin analogues (salcatonin).

Physical exercise can be very beneficial (stimulates osteoblast activity).​

Question 22

What is Paget’s disease?

Answer 22

New bone tissue gradually replaces old bone tissue.

Over time, bones can become fragile and misshapen.

The pelvis, skull, spine and legs are most commonly affected.

Abnormal synchronisation of the osteolytic/osteoblastic phases, characterised by gross deformity of bones.

Treatment: vitamin D, or calcitriol and calcitonin (salcatonin).​

Question 23

What is rickets?

Answer 23

Rickets is the softening and weakening of bones in children, usually because of an extreme and prolonged vitamin D deficiency.

Rare inherited problems also can cause rickets.

Treatment: vitamin D or calcitriol.

Question 24

What is osteomalacia?

Answer 24

Osteomalacia refers to a marked softening of your bones, most often caused by severe vitamin D deficiency.

The softened bones of children and young adults with osteomalacia can lead to bowing during growth, especially in weight-bearing bones of the legs.

Osteomalacia in older adults can lead to fractures.

Treatment: vitamin D or calcitriol.

Question 25

What is achondroplasia?

Answer 25

Achondroplasia is the most common form of skeletal dysplasia, occurring in about one in every 40,000 births.

Achondroplasia impairs the growth of bone in the limbs and causes abnormal growth in the spine and skull.

Most common form of dwarfism, involves conversion of cartilage to bone, usually with a normal size trunk and head, with very short extremities. ​

Mainly due to a mutation of a growth factor receptor (FGFR3) essential for bone growing. GH treatment has only a very slight and short-lasting effect in the very young child.​