Precipitation and Absorption of Calcium and Phosphate in Bone-Equilibrium with the Extracellular Fluids
Hydroxyapatite Does Not Precipitate in Extracellular Fluid Despite Supersaturation of Calcium and Phosphate Ions. The concentrations of calcium and phosphate ions in extra-cellular fluid are considerably greater than those required to cause precipitation of hydroxyapatite. However, inhibitors are present in almost all tissues of the body as well as in plasma to prevent such precipi-tation; one such inhibitor is pyrophosphate. Therefore, hydroxyapatite crystals fail to precipitate in normal tissues except in bone despite the state of supersatu-ration of the ions.
Mechanism of Bone Calcification. The initial stage in boneproduction is the secretion of collagen molecules (called collagen monomers) and ground substance (mainly proteoglycans) by osteoblasts. The collagen monomers polymerize rapidly to form collagen fibers; the resultant tissue becomes osteoid, a cartilage-like material differing from cartilage in that calcium salts readily precipitate in it. As the osteoid is formed, some of the osteoblasts become entrapped in the osteoid and become quiescent. At this stage they are called osteocytes.
Within a few days after the osteoid is formed, calcium salts begin to precipitate on the surfaces of the collagen fibers. The precipitates first appear at inter-vals along each collagen fiber, forming minute nidi that rapidly multiply and grow over a period of days and weeks into the finished product, hydroxyapatitecrystals.
The initial calcium salts to be deposited are not hydroxyapatite crystals but amorphous compounds (noncrystalline), 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 reprecipitation, these salts are converted into the hydroxyapatite crystals over a period of weeks or months. A few per cent may remain permanently in the amorphous form. This is important because these amorphous salts can be absorbed rapidly when there is need for extra calcium in the extracellular fluid.
The mechanism that causes calcium salts to be deposited in osteoid is not fully understood. One theory holds that at the time of formation, the colla-gen fibers are specially constituted in advance for causing precipitation of calcium salts. The osteoblasts supposedly also secrete a substance into the osteoid to neutralize an inhibitor (believed to be pyrophosphate) that normally prevents hydroxyapatite crystallization. Once the pyrophosphate has been neutralized, the natural affinity of the collagen fibers for calcium salts causes the precipitation.
Precipitation of Calcium in Nonosseous Tissues Under Abnormal Conditions. Although calcium salts almostnever precipitate in normal tissues besides bone, under abnormal conditions, they do precipitate. For instance, they precipitate in arterial walls in the condition called arteriosclerosis and cause the arteries to become bone-like tubes. Likewise, calcium salts frequently deposit in degenerating tissues or in old blood clots. Presumably, in these instances, the inhibitor factors that normally prevent deposition of calcium salts disappear from the tissues, thereby allowing precipitation.