The maintenance of calcium and phosphate homeostasis involves (See " Relation between total and ionized serum calcium concentrations".). As you can see from the above discussion, calcium and phosphorus have an inverse relationship: when calcium levels increase, phosphorus levels decrease, . Calcium and phosphorus are essential minerals found in the bone, blood and soft tissue of the body and have a role in numerous body functions. Phosphorus.
To prevent detrimental increases in phosphate, parathyroid hormone also has a potent effect on the kidney to eliminate phosphate phosphaturic effect. Maximizes tubular reabsorption of calcium within the kidney. This activity results in minimal losses of calcium in urine. Vitamin D acts also to increase blood concentrations of calcium. It is generated through the activity of parathyroid hormone within the kidney. Far and away the most important effect of vitamin D is to facilitate absorption of calcium from the small intestine.
In concert with parathyroid hormone, vitamin D also enhances fluxes of calcium out of bone. Calcitonin is a hormone that functions to reduce blood calcium levels. It is secreted in response to hypercalcemia and has at least two effects: Suppression of renal tubular reabsorption of calcium. In other words, calcitonin enhances excretion of calcium into urine. Inhibition of bone resorption, which would minimize fluxes of calcium from bone into blood.
Although calcitonin has significant calcium-lowing effects in some species, it appears to have a minimal influence on blood calcium levels in humans. A useful way of looking at how hormones affect tissues to preserve calcium homeostasis is to examine the effects of calcium deprivation and calcium loading.
The following table summarizes body responses to conditions that would otherwise lead to serious imbalances in calcium and phosphate levels in blood.
Osteoblasts originate from a mesenchymal stem cell that can also differentiate into a chondrocyte, myocyte, fibroblast, or adipocyte. The terminology for these lineages is still evolving and is herein [over] simplified.
Many intermediate steps and regulatory factors are involved in lineage development. The cells develop processes that communicate as canaliculi with other osteocytes, osteoblasts, and the vasculature. Osteocytes thus present acres of cellular syncytium that permits translocation of bone mineral during times of metabolic activity and can provide minute-to-minute exchanges of minerals from bone matrix.
Calcium and Phosphate Homeostasis
Osteocytes are extremely important in normal skeletal homeostasis. Their function is reviewed recently by Bonewald These cells are the likely transducers through their canaliculi of mechanical forces on bone and mediate the complex remodeling response to mechanical stimuli of the skeleton that causes appropriate changes in formation and resorption in response to skeletal loading.
These cells produce sclerostin SOST genewhich decreases bone formation Defects in sclerostin function either by a mutation in SOST or a mutation downstream downstream to sclerostin cause the high bone mass disorders sclerosteosis and van Buchem disease respectively Sclerostin antagonism represents an experimental target for osteoporosis therapy 15, The osteoclast resorbs bone.
It is a terminally-differentiated, large, multinucleated giant cell that arises from hematopoietic marrow precursors under the influences of hormones, growth factors, and cytokines 3.
The osteoclast resorbs bone by attachment with a ruffled border through adhesion molecules and by secretion of hydrogen and chloride ions that dissolve mineral and lytic proteases, notably lysosomal proteases active at low pH and metalloproteinases and cysteine proteinases that dissolve matrix. One enzyme involved in bone resorption, cathepsin Khas been an investigational target for treatment of osteoporosis In contrast to the receptor-rich osteoblast, the mature osteoclast has few receptors, but it robustly expresses the receptor for CT.
After completing its function, the terminally-differentiated osteoclast undergoes apoptosis. Bone-lining cells are flat, elongated cells that cover inactive bone surfaces. Their function is unknown, but they may be osteoblast precursors or function to clean up resorption and formation debris. Mast cells can be seen at sites of bone resorption and may also participate in this process.
Cells of the immune system play a key role in bone metabolism, especially resorption, by their interactions with bone cells that are described later.
Bone grows and models under the influence of metabolic, mechanical, and gravitational forces during growth through adolescence, changing its size and shape in the process. Bone growth continues until approximately the third decade. Bone mass continues to increase until the fourth decade Figure 4. Schematic representation in relative units of normal skeletal development, demonstrating changes in bone resorption and formation.
In osteoporosis, there is an accelerated loss of bone because of increased resorption and decreased formation. Both cortical bone and trabecular bone remodel, but the latter is more metabolically active. Bone remodeling can be divided into several stages that include resorption by osteoclasts and formation by osteoblasts.
The Balance of Calcium & Phosphorus
Remodeling serves to repair skeletal microdamage and to improve skeletal strength in response to mechanical forces. Osteoclasts and osteoblasts communicate with each other during remodeling in a process that is referred to as coupling and mediated by local regulatory signals that are discussed subsequently.
Coupling assures a balance of bone formation and bone resorption in the adult skeleton. The process of bone formation is thus balanced by the process of bone resorption.
Trabecular bone remodels on its surface. Most remodeling occurs in trabecular bone and on the endosteal surfaces of cortical bone, with little periosteal remodeling. However, in diseases like hyperparathyroidism, subperiosteal resorption is activated. The parathyroid gland can sense an imbalance of calcium or phosphorus. If the calcium level is low, the parathyroid gland will release PTH, which tells the kidneys to produce more active vitamin D.
This helps the body to absorb more dietary calcium and phosphorus through the intestine, tells the bone to release calcium and phosphorus into the blood and tells the kidneys to excrete more phosphorus in the urine. Calcium, Phosphorus and the Kidneys Healthy kidneys will eliminate excess phosphorus and calcium in the blood. If kidney function is impaired, the body will not be able to get rid of extra phosphorus.
High phosphorus levels stimulate the release of parathyroid hormone, which can cause complications when the normal mechanism for bone mineral management does not work correctly. A high phosphorus level may also result in a low calcium level.
Calcium binds with phosphate and is deposited in the tissue.