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In accordance with the prevailing frequency and importance of diseases of the skeletal system as compared with lesions of muscles and soft tissues, most of this chapter is devoted to bone pathology.

The skeleton consists of 206 bones, differing in size and shape (tubular, flat, cuboid). Bones play an important role in mineral homeostasis, are the site of hematopoiesis, provide mechanical support for movement and protection, determine the size and shape of the human body. They are connected by many joints that are involved in providing movement and stability.

Bone tissue is one of the types of connective tissue that is calcified (mineralized) under normal conditions. Using biochemical methods, it was established that bone tissue consists of an organic matrix (35%) and inorganic elements (65%). One of the inorganic components is calcium hydroxyapatite [Ca10 (PO4) 6 (OH) 2], a mineral that not only provides strength and hardness, but is also a “storage” of 99% of calcium ions, 80% of phosphorus, 65% of sodium and magnesium. The formation of hydroxyapatite crystals in the bones occurs by converting a liquid material into a dense material (by analogy with the crystallization of water upon freezing). This process is caused by the organic matrix and is governed by many factors, many of which are not yet known. The level of mineralization can vary, but its duration, as a rule, is 12–15 days. The bone that remains unmineralized is called the osteoid. Organic components of bone tissue include matrix proteins and cells. Most of the bone matrix proteins are represented by type I collagen and a small amount of non-collagen proteins. Cellular elements make up only 2% of bone mass. They provide renewal and maintenance of this tissue throughout life. The bone-forming elements are precursor cells, osteoblasts and osteoclasts.

Progenitor cells are pluripotent (totipotent, polypotent; I mean their different possibilities with respect to the directions of differentiation) mesenchymal stem cells. They are located near the bone surfaces and, with appropriate stimulation, are capable of producing offspring by dividing, differentiating into osteoblasts, which is extremely important for physiological growth, renewal and restoration of bone.

Osteoblasts are located on the surface of the bone. They synthesize, transport and distribute many matrix proteins. These cells also initiate the mineralization process. At certain times, osteoblasts are collected in groups of up to 400 cells. The functional activity of these groups is coordinated, since by this time the bone already consists of structural units, giving it greater strength and stability. Osteoblasts have receptors for hormones (parathyroid hormone, estrogen), vitamin D, cytokines, and growth factors that regulate the differentiation, growth, and metabolism of bone cells. Once the osteoblasts are surrounded by the matrix, they become osteocytes. They have long cytoplasmic processes that give the cells a spider-like appearance.

Osteocytes are not involved in metabolism, but they play an important role in controlling daily fluctuations in serum levels of calcium and phosphorus. Being imprisoned in the bone tissue, osteocytes communicate with superficial cells and between themselves using a complex network of tubules passing through the matrix. The processes of osteocytes cross the canaliculi, and the contacts of these cells in the zones of slit-like joints (nexus) provide for the transfer of substrates and potentials of the surface membrane (plasmolemma).

Osteoclasts are cells responsible for bone resorption (resorption). These are cell derivatives - precursors of granulocyte monocytes, localized in the hematopoietic part of the bone marrow. They contain 6–12 nuclei and are closely related to the bone surface. Resorption pits, which are created and often populated by these cells, appear in the morphological literature under the name of Gaussian lacunae (J.Howship). They usually have scalloped edges. On that part of the osteoclast plasmolemma, which is located on the resorptive surface, a number of villous processes appear. So you create an i-corrugated border that serves to increase the surface membrane area. The plasmolemma, which surrounds this area along the entire edge, forms a zone of hermetic closure with the underlying bone, preventing the “expansion” of the osteolytic action of enzymes and other substances performing resorption. Self-sustaining extracellular resorption space, hermetically limited on all sides, resembles a secondary lysosome. Osteoclasts oxidize the environment of this space by “pumping” hydrogen ions into it, which contributes to the dissolution of minerals. In addition, osteoclasts secrete into the space of many enzymes that catalyze the splitting of the protein matrix into amino acids, as well as the release and activation of growth factors and enzymes. Among the latter, we call collagenase, which at the time of release is deposited and is associated with the matrix with the help of osteoblasts. Thus, as soon as the bone breaks down into elementary units, certain substances are released, which initiate its renewal (regeneration).

Collagen type I forms the core of the matrix and makes up 90% of its organic component. Osteoblasts are capable of depositing collagen, either as a disordered plexus, forming a coarse-fibered bone, or as a connected and complex complex, forming a lamellar bone. The coarse fibrous bone is found in the skeleton of embryos and fetuses. In an adult, it can be found in the zones of bone growth (Fig. 24.1, A). The advantages of coarse-fiber bones are expressed in the speed of formation and equal strength in all directions. The presence of areas of such bone in adults always indicates a pathological process, but is not a diagnostic marker. For example, in circumstances that require rapid reparative stabilization, such as a fracture, coarse fibrous bone is primarily formed. It also forms around the sites of infection and forms the matrix of bone-forming tumors.

The lamellar bone, which gradually in the process of growth replaces the coarse-fiber bone, is formed much slower, but it has greater strength.
This tissue is represented in the adult body by two main types: compact and spongy bone. The compact bone forms a cortical (surface) layer of tubular bones. This layer is built from three systems. A system of osteons is located under the external bony plates (haversian system; S.Havers). Osteons are formed by concentric bone plates and contain in the center the vascular channels of osteon (gaversovy channels). Between osteons there are intercalated bone plates. Under the system of osteons is a system of internal common plates. In addition to the vascular canals of osteon, compact bone permeates the nutritional canals (Folkmann channels; AW Volkmann), through which blood vessels and nerves pass (Fig. 24.1, B, C).

Below the system of osteons are bone trabeculae, which are a spongy bone. In the long tubular bones of the skeleton, the spongy bone fills the inner part of the epiphysis (the widest articular end of these bones) and the metaphysis (the part of the diaphysis adjacent to the epiphyseal cartilage). Diaphases of such tubular bones contain spongy bone in the base



Fig. 24.1.

Bone structure

.

And - coarse fibrous bone; B - compact bone.



Fig. 24.1. Continued.

AT -

two osteons of compact bone

in the center of which bone canals are visible (haversian channels), and in the concentric plates there are process osteocytes.

on the margins of the bone marrow cavities, i.e. closer to the metaphysics. 13 flat bones (for example, in the parietal bone or scapula) the space between two plates of a compact substance is entirely occupied by a spongy bone.

Non-collagen bone proteins are associated with the matrix and are grouped according to their functions as adhesive, calcium-bound, mineralized, enzymes, cytokines, and growth factors. Only osteocalcin is specific for bone tissue. It is determined in serum and serves as a reliable marker of osteoblastic activity. Cytokines and growth factors control the proliferation of bone cells, their differentiation and metabolism. They play an important role in the transmission (translation) of mechanical and metabolic signals to ensure local bone cell activity and adaptation processes.

Formation (modeling) and renewal (remodeling) of bone tissue. Osteoblasts and osteoclasts interact in a coordinated manner and are now regarded as a single functional bone system, known as the “basic multicellular unit”. The processes of bone formation and resorption are closely related to each other, and their balance determines the skeletal mass in different periods of life. During growth and growth of the skeleton (modeling), bone formation prevails. When the skeleton matures, the processes of destruction and renewal (remodeling) equalize. It happens like this. The peak of bone mass is achieved in a young adult body, and 5–10% of the total skeleton mass is updated annually. At the same time, the amount of bone substance that is absorbed and newly created by the main multicellular units becomes approximately equal. However, from the third decade of life, resorption begins to prevail over osteogenesis, which results in a gradual decrease in skeletal mass.

Osteoblasts provide the largest part of local control in the formation and maintenance of the skeleton system, since they not only produce the bone matrix, but also play an important role in the mediation of osteoclast activity. Many of the primary bone resorption stimulants - parathyroid hormone or parathyroid hormone with an associated protein, interleukin-1, interleukin-6, and tumor necrosis factor-p (TNF-p) - have minimal effect or do not have a direct effect on osteoclasts. Indeed, osteoblasts possess receptors for these substances, and as soon as they receive the appropriate signal, they release a soluble mediator that induces bone resorption by osteoclasts. Cytokines and growth factors [especially transforming growth factor-p (TGF-p)], released from the matrix during osteoid cleavage, on the principle of feedback, trigger the activation of osteoblasts for synthesis and deposition in the resorptive gaps of an equivalent amount of new bone [by Cotran RS, Kumar V., Collins T., 1998]. Bone tissue renewal and resorption, carried out in the order described, are not only related to each other in time and space, but also subject to control by local and systemic factors.

Growth and development of bones. Bone tissue is created by osteoblasts. After its creation, a further increase in bone mass is achieved only due to the deposition of new bone on the pre-existing matrix. Such a mechanism of approximate growth of bone mass is the key to understanding the various mechanisms of skeletal development.

The forerunner of the early skeleton is the primitive mesenchyme. Bones such as the cranial and some parts of the clavicles originate from an intramembrane formation and are formed by osteoblasts directly from the mesenchyme. On the contrary, in the process of creating an enchondral bone, the mesenchyme first forms the cartilage model, or the germ of the future bone. Subsequently, at about the 8th week of pregnancy, the cartilage in the center of the fetal bone undergoes degenerative changes, is mineralized and removed by osteoclast-type cells. This process, which progresses towards both future epiphyses, is accompanied by the growth of blood vessels and precursors of osteogenic elements, which ensure the creation of osteogenic cells.

A similar sequence of events occurs in the epiphysis. The plate of the cartilage model is immured between the expanding zones of ossification and is known as physis, or the growth plate. Chondrocytes within growth plates undergo a number of changes: proliferation, growth, degradation and mineralization. Cartilage salinity becomes a signal for a physiological counterweight — resorption of mineralized cartilage. The remains of mineralized cartilage are the basis for the deposition of bone on their surfaces. These structures form the primary spongy bone. The process of enchondral ossification is also found at the base of the articular cartilage. Through these mechanisms, the bones increase the length and the articular surfaces the diameter.

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