The deposition and absorption of calcium and phosphate in bone are in balance with extracellular fluid
Although the mechanism by which calcium salts are deposited in osteoid is not fully understood, the control of this process seems to depend largely on pyrophosphate, which inhibits hydroxyapatite crystal formation and bone calcium deposition.
Hydroxyapatite does not precipitate in the extracellular fluid despite being oversaturated with Calcium and Phosphate ions. The concentration of calcium and phosphate ions in the extracellular fluid is significantly greater than that under conditions for precipitation of hydroxyapatite. However, inhibitors exist in most body tissues, such as plasma, to prevent these precipitations, eg: pyrophosphate. Therefore, crystalline hydroxyapatite cannot precipitate in normal tissues except in bone despite their supersaturated concentrations.
Mechanism of bone calcium deposition
Initiated by the secretion of collagen molecules (collagen monomers) and matrix (mainly proteoglycans) by osteoblasts. Collagen monomers are rapidly polymorphic to form collagen fibres; The result is “osteoid,” a material that resembles cartilage but differs in that it allows calcium salts to be deposited rapidly on it. As the osteoid forms, some of the osteoblasts become trapped within it and become dormant. At this stage, they are called bone cells (osteocytes).
Within a few days after osteoid formation, calcium salts begin to deposit on the surface of collagen fibres. The first deposition occurs only at some point along with the collagen fibre, (forming nidi minute) after this process takes place more often, growing day by day, week by week until the final product is formed, Hydroxyapatite crystals.
The calcium salts that are initially deposited are not hydroxyapatite crystals but are in the form of amorphous (noncrystalline) compounds, a mixture of salts such as CaHPO4 × 2H2O, Ca3(PO4)2 × 3H2O, and others. Then, by a process of substitution and addition of atoms, or reabsorption and re-precipitation, the salts are converted to hydroxyapatite crystals over a period of weeks or months. A few percent may remain permanently amorphous, which is important because amorphous salts can be rapidly absorbed as calcium requirements increase in the extracellular fluid.
Although the mechanism by which calcium salts are deposited in osteoid is not fully understood, the control of this process seems to depend largely on pyrophosphate, which inhibits hydroxyapatite crystal formation and bone calcium deposition. The thresholds for pyrophosphate are, in turn, regulated by at least three other molecules. One of the most important molecules is a substance called tissue nonspecific alkaline phosphatase (TNAP), which helps break down pyrophosphate and keep its threshold within limits so calcium deposition can occur when needed. TNAP is secreted by osteoblasts into osteoid to neutralize pyrophosphate, and when pyrophosphate has been deactivated, spontaneous binding between collagen fibres and calcium salts causes hydroxyapatite crystallization. The importance of TNAP in bone mineralization is illustrated by tests of mice lacking the TNAP gene,
The osteoblasts also secrete at least two other substances involved in the regulation of bone calcification:
(1) nucleotide phosphodiesterase pyrophosphatase 1 (NPP1), an extracellular producer of pyrophosphate, and (2) protein ankylosis (ANK), which contributes to the extracellular catabolism of pyrophosphate by transporting it from the interior to the surface. the surface of the cell. Deficiency of NPP1 or ANK causes decreased extracellular pyrophosphate and excess calcification of bones, such as bone spurs, or even calcification of other tissues such as tendons and ligaments of the spine, which occurs in people with a form of inflammation joints called ankylosing spondylitis.
Calcium deposition in non-skeletal tissues under abnormal conditions
Although calcium salts do not normally precipitate in normal tissues adjacent to bone, under abnormal conditions they may precipitate. For example, precipitates in artery walls in arteriosclerosis and causes arteries to become tubular like bones. Likewise, calcium salts are frequently deposited in degenerated tissues or old blood clots. Presumably, in this case, the inhibitor prevents the deposition of calcium salts from disappearing in the tissues, thus allowing the deposition.