Bone metabolism
Bone consists of both organic and organic components. The major inorganic compound is calcium phosphate which accounts for 2/3rd of the bone weight. This calcium phosphate interacts with calcium hydroxide to from hydroxyapatite.
Other inorganic compounds include calcium carbonate, sodium, magnesium and fluoride.
The remaining organic portion of the bone is made up of cells such as osteoblasts, osteocytes, osteoclasts etc and osteoid such as collagen fibers, proteoglycans, glycoproteins etc. The osteoid is secreted by osteoblasts.
Bone mineral metabolism is important for calcium homeostasis. During remodelling of the bone, minerals are released into the ECF through the action of osteoclasts and these minerals are removed from the blood by the osteoblasts during bone formation. Under normal conditions the rate of bone resorption is equal to the rate of bone formation.
There are three major hormones that regulate calcium homeostasis- Parathyroid hormone(PTH), Calcitonin and Vitamin D metabolite (1,25, Dihydroxy cholecalciferol).
Effect of PTH in the bone
- PTH is released from the parathyroid gland in response to low blood calcium levels. The action of PTH on the bone is calcium resorption from the skeletal reserves into the ECF. Release of calcium from the bone occurs in 2 phases. They are:
- Rapid phase and
- Slow phase.
- Rapid phase
- This phase is termed as osteocytic osteolysis. It results from activation of the already existing osteocytes and osteoclasts present in the bone. During this phase there is an increased flow of calcium from the bone fluid to the ECF by osteocyte-osteoblast pump.
- PTH causes removal of bone salts from two areas in the bone, one from the bone matrix in the vicinity of the osteocytes lying in the bone itself and two, in the vicinity of the osteoblasts along the bone surface. When this osteocyte – osteoblast pump is activated by PTH, bone fluid calcium concentration falls and calcium and phosphorous salts are absorbed from the bone.
- When the pump is inactivated, bone fluid calcium concentration rises and calcium and phosphorous salts are redeposited in the matrix.
- PTH has receptors on the cell membrane of both osteoblast and osteocytes When stimulated by PTH, calcium permeability of the osteocytic membrane increases thus allowing calcium to diffuse into the membrane cells from the bone fluid to the ECF.
- Slow phase
- This phase results from proliferation of the osteoclasts followed by increased osteoclastic reabsorption of the bone itself. PTH do not have receptors on the osteoclasts. Activation of osteoclastic system occurs in two stages,
- Immediate activation of the osteoblasts that are already formed.
- Formation of new osteoblasts.
- PTH stimulates the conversion of osteoprogenitor cells to osteoclasts. PTH binds to the receptors present on the surfaces of osteoblasts causing the cells to contract and thereby exposes the minerals in the matrix to osteoclasts. The minerals and organic components released from the bone are phagocytized by osteoclasts and transported across the cell to be released into the ECF. When the animal is in the positive calcium balance, PTH secretion subsides and osteoblasts finish the reversal and formation phases of bone remodeling.
- This phase results from proliferation of the osteoclasts followed by increased osteoclastic reabsorption of the bone itself. PTH do not have receptors on the osteoclasts. Activation of osteoclastic system occurs in two stages,
Calcitonin
Calcitonin is the second major hormone that regulates calcium. It is the secreted by the ‘C’ cells within the thyroid gland in response to high blood calcium levels.
Calcitonin has receptors on the osteoclasts and directly act on these cells to inhibit bone resorption by blocking osteoclastic osteocytic activity.
1,25 dihydroxy cholecalciferol
1,25 dihydroxy cholecalciferol is the third major hormone involved in calcium metabolism and is a vitamin D metabolite. The action of 1,25 DHCC in bone formation is primarily indirect. It acts on the intestine to increase the efficiency of absorption of calcium and phosphorous absorption via calcium binding protein .
Osteoblasts have receptors for 1,25 DHCC. It causes osteoclastic resorption and calcium mobilization from the bone.
Not only bone helps in the maintenance of blood calcium level it also acts as a buffer of the blood pH. It can release cations or anions in response to acidosis or alkalosis.
Effect of estrogen
Estrogen receptors are present on osteoblasts and osteoclasts. In the osteoclast, estrogen increases cell proliferation and enhances expression of genes that encode for growth factors, enzymes, matrix proteins and cytokines that alter bone remodeling.
Estrogen inhibit production of cytokines associated with bone resorption such as interlukins (IL–I, IL-6 and IL-11). Estrogen also stimulates synthesis of transforming growth factor-beta (TGF- ß), Insulin like growth factor (IGF)–I and IGF-binding proteins. Proteins involved in bone remodeling, such as bone morphogenic protein and osteoprotegenin are also regulated by estrogen. In estrogen deficiency these is an upward regulation in the maturation of osteoclasts and osteoblasts, with an over all increase in bone remodeling.
The major action of estrogen on bone is inhibition of bone resorption. Estrogen induces apoptosis and reduces the lifespan of the osteoclast. The synergy of several cytokines enhance osteoclast recruitment, differentiation and activity. The blockage of the productive of cytokines such as IL and tumour necrosis factor µ (TNF µ) by osteoblasts prevents bone resorption in an estrogen deficient state.