Ossification

OSSIFICATION (ossificatio), the formation of bone, a process that occurs in the body during normal formation and growth of bones, as well as under various pathological conditions both within the skeletal system and outside it, in various organs and tissues (heterotopic or heteroplastic formation of bone). During embryonic development of bones, the process of O. has different characteristics depending on whether bone development occurs in a connective tissue or cartilaginous precursor. In the first case, the process of O. occurs in a simpler manner than in the development of bone from cartilaginous precursors, where bone formation, beginning in the so-called primary points of O., occurs through a more complex pathway called endochondral bone formation (for more details - see Bone). But in the final result, in both cases, O. occurs through the appositional activity of osteoblasts producing osteoid tissue, which, after being impregnated with lime salts, is transformed into mature bone. With further growth of bones, ossification occurs in the lines or zones of endochondral O., located at the border between the epiphyses and diaphyses of bones, as well as in the so-called centers of O., appearing in the cartilaginous epiphyses of bones. Along with the process of endochondral ossification, which determines the growth of bones in length, ossification also occurs in the periosteum through the formation of bone trabeculae from the connective tissue of the periosteum, which determines the growth of bones in thickness. The process of O. in the zones of endochondral ossification of long tubular bones usually begins to gradually end in various parts of the skeletal system from the age of 17, and by the age of 19-23, ossification ceases, and with it, bone growth also ceases. But inside the bones, ossification continues further in connection with the processes of bone restructuring that occur throughout life, accompanied by the destruction of old bone trabeculae and the formation of new ones. O. occurring under various pathological processes and conditions basically has the same types as ossification during normal bone formation, but can sometimes differ from the latter in some atypicality in the sense that different types of ossification processes can occur simultaneously and in close proximity to each other, which sometimes creates a very variegated histological picture. Increased O. in the skeletal system is observed in various processes of a hypertrophic nature; in these cases, bone tissue is formed through the activity of osteoblasts, as well as through the metaplasia of connective and cartilaginous tissue into bone. The result of increased ossification in these cases is either diffuse thickening of the bone in the form of hyperostosis or the formation of various osteophytes. Processes of a hypertrophic nature with increased ossification also include changes in bones in congenital gigantism, acromegaly, and leontiasis ossium. In various inflammatory and destructive processes in bones (suppurative processes, inflammatory granulomas, tumors, etc.), along with the destruction of bone substance, the formation of new bone tissue is usually also observed, which represents a reactive-organizational or regenerative process. Regenerative ossification is particularly prominently manifested in the process of healing bone fractures. In some pathological processes, a disturbance of O. is observed, either in the form of insufficient formation of bone substance due to reduced activity of osteoblasts (osteogenesis imperfecta, osteopsathyrosis idiopathica), or in the form of incomplete, remaining at the stage of osteoid substance, development of bone trabeculae (rickets, osteomalacia), or in the form of a disturbance of the mechanism of endochondral ossification (achondroplasia). Separate from the processes of O. related to the skeletal system is the formation of bone outside it, called heterotopic or heteroplastic formation of bone. Close to this category is the O. of the cartilages of the ribs, trachea, and intervertebral plates as predominantly an age-related phenomenon. In most cases, heterotopic formation of bone is associated with the presence of dystrophically calcified necrotic foci. A classic example of this kind is the metaplastic formation of bone in the connective tissue capsule of a healed primary tuberculous focus in the lung. Similar heterotopic formation of bone is observed in the most diverse organs and tissues; I. F. Pozharsky believes that bone can form in any place where young granulation tissue meets with dystrophically calcified necrotic foci. In the process of resorption of such a focus, part of the granulation tissue cells transforms into osteoblasts and begins to produce bone, while the other part of the granulation tissue usually transforms into bone marrow tissue. As a rule, O. in such cases occurs without an intermediate cartilaginous stage. Apparently, for the occurrence of the O. process around dystrophically calcified foci, both the nature of the calcium deposits and the nature of the reactivity of the organism are important. Such heterotopic formation of bone can also be induced experimentally, for example, in the kidney when the renal artery is ligated. In other cases, heterotopic formation of bone can occur without the presence of a calcified focus. This category includes the development of bone in tendons, fasciae, muscles (myositis ossificans circumscripta and progressiva), at the edges of old ulcers, and in postoperative scars of the linea alba. In all these cases, bone formation often occurs simultaneously both through the metaplasia of connective tissue into bone and through the preliminary formation of cartilage and subsequent endochondral O. In such cases, O. represents an organizational-reactive process in which bone is a special product of pathological organization formed in response to various irritations of tissues of a mechanical or traumatic nature (ossifying traumatic myositis, rider's bone, etc.). d. Vyropayev. The bone substance formed during both normal and pathological O. has almost the same composition of inorganic compounds (85-90% phosphates and 10-15% carbonates of Ca). The process of O. is very complex and far from fully understood. Previously, it was believed that the deposition of Ca salts in cartilaginous and osteoid tissues during O. occurs chemically as a result of the interaction of calcium compounds with acid-reacting compounds of phosphoric acid, which is supported by the strong basophilia of ossifying tissues. However, the amount of Ca₃(PO₄)₂ formed during O. is much greater than can be formed from the phosphorus of the tissues. Furthermore, when rich in phosphorus tissues (thyroid gland, spleen) are introduced into the abdominal cavity of rabbits, the latter are not impregnated with lime, whereas the substance of cartilage under the same conditions is always impregnated with it to a marked degree (Wells). According to other views, the main importance for the fixation of Ca salts during O. is the decrease in their solubility due to a decrease in CO₂ content (Hofmeister) or an increase in the alkalinity of tissues (for example, in necrosis due to the formation of NH₃). However, neither these views nor the assumption of the formation of Ca albuminates in ossifying tissues fully explain the phenomena observed during this process. The latter are best considered from a physicochemical point of view as the adsorption of Ca⁺⁺ by osteoid or cartilaginous tissue: of all tissues placed in solutions of lime salts, the most Ca is adsorbed by young cartilaginous tissue. The processes occurring during this were studied by many authors (Freudenberg and Gyorgy, Heubner and Rona, Pfaundler). During the adsorption of Ca⁺⁺ from a calcium salt solution, an exchange of Ca⁺⁺ for H⁺ occurs. As a result, the solution becomes acidic, CO₃ is displaced from it, and phosphates predominate over carbonates. Moreover, the resulting calcium bicarbonate is relatively easily soluble and significantly reduces the solubility of Ca₃(PO₄)₂. A similar process apparently also occurs in the body during O.: Ca⁺⁺ is adsorbed by cartilage from the blood, where in turn it is in an adsorptive combination with protein. At the same time, H⁺ is released from the cartilage (the isoelectric point of cartilage corresponds to pH=4.6) and CO₂ is displaced from the surrounding fluid. These phenomena and the greater insolubility of phosphates in a fluid containing CO₂ explain the predominance of phosphate deposition over carbonates during O. In the process of O., importance is attached to phosphatase, an enzyme that cleaves phosphoric acid from its complex esters. (For the importance of vitamin D - see Avitaminoses, Vitamins.)

N. Anichkov.