Nursing process for benign tumors. Specialized medical care for malignant neoplasms

Bone tissue is a specialized type of connective tissue, the organic intercellular substance of which contains up to 70% inorganic compounds - calcium and phosphorus salts and more than 30 trace element compounds. The organic matrix contains collagen-type proteins (ossein) and chondroitin sulfates. In addition, it contains citric acid and other acids, which form complex compounds with calcium that impregnate the intercellular substance.

There are 2 types of bone tissue: coarse-fibrous (reticulofibrous) and lamellar.

In the intercellular substance of bone tissue there are Cellular elements : osteogenic cells, osteoblasts and osteocytes, which are formed from mesenchyme and represent bone differentiation. Another population of cells are osteoclasts.

Osteogenic cells – these are stem cells of bone tissue that separate from the mesenchyme at the early stage of osteogenesis. They are capable of producing growth factors that induce hematopoiesis. During the process of differentiation they turn into osteoblasts.

Osteoblasts localized in the inner layer of the periosteum, during bone formation they are located on its surface and around the intraosseous vessels; the cells are cubic, pyramidal, angular in shape, with well-developed hydroelectric power and other organelles of synthesis. They produce collagen proteins and components of the amorphous matrix and actively divide.

Osteocytes - are formed from osteoblasts, are located inside the bone in peculiar bone lacunae, and have a process form. Lose the ability to divide. The secretion of the intercellular substance of bone is weakly expressed.

Osteoclasts – polynuclear macrophages of bone tissue, formed from blood monocytes. Can contain up to 40 or more cores. The volume of cytoplasm is large; the zone of cytoplasm adjacent to the bone surface forms a corrugated border formed by cytoplasmic processes, which contain many lysosomes.

Functions - destruction of fibers and amorphous bone substance.

Intercellular substance It is represented by collagen fibers (types I and V collagen) and an amorphous component, which contains calcium phosphate (mainly in the form of hydroxyapatite crystals and a little in the amorphous state), a small amount of magnesium phosphate and very few glycosaminoglycans and proteoglycans.

Coarse-fibrous (reticulofibrous) bone tissue is characterized by a disordered arrangement of ossein fibers. In lamellar (mature) bone tissue, ossein fibers in bone plates have a strictly ordered arrangement. Moreover, in each bone plate the fibers have the same parallel arrangement, and in the adjacent bone plate they are at right angles to the previous one. The cells between the bone plates are localized in special lacunae; they can be immured in the intercellular substance or located on the surface of the bone and around the vessels that penetrate the bone.

Bone as an organ Histologically it consists of three layers: periosteum, compact substance and endosteum.

Periosteum It has a structure similar to the perichondrium, that is, it consists of 2 similar layers, the inner of which, osteogenic, is formed by loose connective tissue, where there are many osteoblasts, osteoclasts and many vessels.

Endost lines the medullary canal. It is formed by loose fibrous connective tissue, where there are osteoblasts and osteoclasts, as well as other loose connective tissue cells.

Functions of the periosteum and endosteum: bone trophism, bone growth in thickness, bone regeneration.

Compact substance bone consists of 3 layers. The outer and inner ones are the general (common) bone plates, and between them there is an osteon layer.

The structural and functional unit of bone as an organ is Osteon , which is a cavity formation consisting of concentrically layered bone plates in the form of several cylinders inserted into one another. Between the bone plates there are lacunae in which osteocytes lie. A blood vessel passes through the cavity of the osteon. The bony canal that contains the blood vessel is called the osteon canal or Haversian canal. Between the osteons there are intercalated bone plates (remnants of decaying osteons).

Histogenesis of bone tissue. The source of bone tissue development is mesenchymal cells evicted from sclerotomes. Moreover, its histogenesis occurs in two ways: directly from the mesenchyme (direct osteohistogenesis) or from the mesenchyme at the site of previously formed hyaline cartilage (indirect osteohistogenesis).

Direct osteohistogenesis. Directly from the mesenchyme, coarse fibrous (reticulofibrous) bone tissue is formed, which is subsequently replaced by lamellar bone tissue. In direct osteohistogenesis, 4 stages are distinguished:

1. isolation of an osteogenic island - in the area of ​​bone tissue formation, mesenchymal cells actively divide and turn into osteogenic cells and osteoblasts, and blood vessels are formed here;

2. osteoid stage - osteoblasts begin to form the intercellular substance of bone tissue, while some of the osteoblasts find themselves inside the intercellular substance, these osteoblasts turn into osteocytes; the other part of the osteoblasts appears on the surface of the intercellular substance, i.e. on the surface of the formed bone tissue, these osteoblasts will become part of the periosteum;

3. mineralization of the intercellular substance (impregnation with calcium salts). Mineralization is carried out due to the intake of calcium glycerophosphate from the blood, which, under the influence of alkaline phosphatase, is broken down into glycerol and a phosphoric acid residue that reacts with calcium chloride, resulting in the formation of calcium phosphate; the latter turns into hydroapatite;

4. reconstruction and growth of bone - old areas of coarse-fiber bone are gradually destroyed and new areas of lamellar bone are formed in their place; due to the periosteum, common bone plates are formed, due to osteogenic cells located in the adventitia of bone vessels, osteons are formed.

Indirect osteohistogenesis carried out at the site of cartilage. In this case, lamellar bone tissue is immediately formed. In this case, 4 stages can also be distinguished:

1. formation of a cartilaginous model of the future bone;

2. in the area of ​​the diaphysis of this model, perichondral ossification occurs, while the perichondrium turns into periosteum, in which stem (osteogenic) cells differentiate into osteoblasts; osteoblasts begin the formation of bone tissue in the form of common plates that form a bone cuff;

3. in parallel with this, endochondral ossification is observed, which occurs both in the region of the diaphysis and in the region of the epiphysis; ossification of the epiphysis occurs only through endochondral ossification; Blood vessels grow inside the cartilage, in the adventitia of which there are osteogenic cells that turn into osteoblasts. Osteoblasts, producing intercellular substance, form bone plates in the form of osteons around the vessels; simultaneously with the formation of bone, cartilage is destroyed by chondroclasts;

4. reconstruction and growth of bone - old sections of bone are gradually destroyed and new ones are formed in their place; due to the periosteum, common bone plates are formed, due to osteogenic cells located in the adventitia of bone vessels, osteons are formed.

In bone tissue, both processes of creation and destruction constantly occur throughout life. Normally they balance each other. The destruction of bone tissue (resorption) is carried out by osteoclasts, and the destroyed areas are replaced by newly built bone tissue, in the formation of which osteoblasts take part. Regulation of these processes is carried out with the participation of hormones produced by the thyroid, parathyroid and other endocrine glands. The structure of bone tissue is influenced by vitamins A, D, C. Insufficient intake of vitamin D in the body in the early postnatal period leads to the development of the disease Rickets.

The teeth are located in bone sockets - separate cells of the alveolar processes of the upper and lower jaws. Bone tissue is a type of connective tissue that develops from the mesoderm and consists of cells, an intercellular non-mineralized organic matrix (osteoid) and the main mineralized intercellular substance.

5.1. ORGANIZATION AND STRUCTURE OF BONE TISSUE OF THE ALVEOLAR PROCESSES

The surface of the alveolar bone is covered periosteum(periosteum), formed predominantly by dense fibrous connective tissue, in which 2 layers are distinguished: the outer - fibrous and the inner - osteogenic, containing osteoblasts. Vessels and nerves pass from the osteogenic layer of the periosteum into the bone. Thick bundles of perforating collagen fibers connect the bone to the periosteum. The periosteum not only carries out a trophic function, but also participates in bone growth and regeneration. As a result, the bone tissue of the alveolar processes has a high regenerative ability not only under physiological conditions, under orthodontic influences, but also after damage (fractures).

The mineralized matrix is ​​organized into trabeculae - the structural and functional units of spongy bone tissue. Bone tissue cells - osteocytes, osteoblasts, osteoclasts - are located in the lacunae of the mineralized matrix and on the surface of the trabeculae.

The body constantly undergoes processes of bone tissue renewal through time-coupled bone formation and resorption (resorption) of bone. Various bone tissue cells actively participate in these processes.

Cellular composition of bone tissue

Cells occupy only 1-5% of the total volume of bone tissue of the adult skeleton. There are 4 types of bone tissue cells.

Mesenchymal undifferentiated bone cells are located mainly in the inner layer of the periosteum, covering the surface of the bone from the outside - the periosteum, as well as in the composition of the endosteum, lining the contours of all the internal cavities of the bone, the internal surfaces of the bone. They are called lining, or contour, cells. These cells can form new bone cells - osteoblasts and osteoclasts. In accordance with this function, they are also called osteogenic cells.

Osteoblasts- cells located in the zones of bone formation on the external and internal surfaces of the bone. Osteoblasts contain fairly large amounts of glycogen and glucose. With age, this amount decreases by 2-3 times.

ATP synthesis is 60% associated with glycolysis reactions. As osteoblasts age, glycolytic reactions are activated. Reactions of the citrate cycle occur in cells, and citrate synthase has the greatest activity. The synthesized citrate is subsequently used to bind Ca 2+, necessary for mineralization processes. Since the function of osteoblasts is to create the organic extracellular matrix of bone, these cells contain large amounts of RNA necessary for protein synthesis. Osteoblasts actively synthesize and release into the extracellular space a significant amount of glycerophospholipids, which are capable of binding Ca 2+ and participating in mineralization processes. Cells communicate with each other through desmosomes, which allow the passage of Ca 2+ and cAMP. Osteoblasts synthesize and release collagen fibrils, proteoglycans and glycosaminoglycans into the environment. They also ensure the continuous growth of hydroxyapatite crystals and act as intermediaries in the binding of mineral crystals to the protein matrix. As we age, osteoblasts transform into osteocytes.Osteocytes

- tree-like cells of bone tissue, included in the organic intercellular matrix, which contact each other through processes. Osteocytes also interact with other bone tissue cells: osteoclasts and osteoblasts, as well as with mesenchymal bone cells.Osteoclasts

Intercellular and ground substance of bone tissue

Intercellular substance represented by an organic intercellular matrix built from collagen fibers (90-95%) and basic mineralized substance (5-10%). Collagen fibers are mainly located parallel to the direction of the level of the most likely mechanical loads on the bone and provide elasticity and elasticity to the bone.

Main substance The intercellular matrix consists mainly of extracellular fluid, glycoproteins and proteoglycans involved in the movement and distribution of inorganic ions. Mineral substances located as part of the main substance in the organic matrix of bone are represented by crystals, mainly hydroxyapatite Ca 10 (PO 4) 6 (OH) 2. The normal calcium/phosphorus ratio is 1.3-2.0. In addition, Mg 2+, Na +, K +, SO 4 2-, HCO 3-, hydroxyl and other ions were found in the bone, which can take part in the formation of crystals. Bone mineralization is associated with the characteristics of bone tissue glycoproteins and the activity of osteoblasts.

The main proteins of the extracellular matrix of bone tissue are type I collagen proteins, which make up about 90% of the organic matrix of bone. Along with collagen type I, there are traces of other types of collagen, such as V, XI, XII. It is possible that these types of collagen belong to other tissues, which are located in bone tissue, but are not part of the bone matrix. For example, type V collagen is typically found in the vessels that line bone. Type XI collagen is found in cartilage tissue and may correspond to remnants of calcified cartilage. The source of collagen type XII can be “blanks” of collagen fibrils. In bone tissue, type I collagen contains monosaccharide derivatives, has fewer cross-links than other types of connective tissue, and these bonds are formed through allysin. Another possible difference is that the N-terminal propeptide of type I collagen is phosphorylated and this peptide is partially retained in the mineralized matrix.

Bone tissue contains about 10% non-collagen proteins. They are represented by glycoproteins and proteoglycans (Fig. 5.1).

Of the total amount of non-collagen proteins, 10% are proteoglycans. First, large chondroitin is synthesized

Rice. 5.1.The content of non-collagen proteins in the intercellular matrix of bone tissue [according to Gehron R. P., 1992].

containing a proteoglycan, which, as bone tissue forms, is destroyed and replaced by two small proteoglycans: decorin and biglycan. Small proteoglycans are embedded in the mineralized matrix. Decorin and biglycan activate the processes of cell differentiation and proliferation, and are also involved in the regulation of mineral deposition, crystal morphology and the integration of organic matrix elements. Biglycan containing dermatan sulfate is synthesized first; it affects the processes of cell proliferation. During the mineralization phase, biglycan appears, bound to chondroitin sulfate. Decorin is synthesized later than biglycan, during the stage of protein deposition to form the intercellular matrix; it remains in the mineralization phase. It is believed that decorin “polishes” collagen molecules and regulates the diameter of fibrils. During bone formation, both proteins are produced by osteoblasts, but when these cells become osteocytes, they synthesize only biglycan.

Other types of small proteoglycans have been isolated from the bone matrix in small quantities, which act as

receptors and facilitate the binding of growth factors to the cell. These types of molecules are found in the membrane or attached to the cell membrane through phosphoinositol bonds.

Bone tissue also contains hyaluronic acid. It probably plays an important role in the morphogenesis of this tissue.

In addition to proteoglycans, a large number of different proteins related to glycoproteins are detected in bone (Table 5.1).

Typically, these proteins are synthesized by osteoblasts and are capable of binding phosphate or calcium; thus they take part in the formation of the mineralized matrix. By binding to cells, collagens and proteoglycans, they ensure the formation of supramolecular complexes of the bone tissue matrix (Fig. 5.2).

The osteoid contains proteoglycans: fibromodulin, biglycan, decorin, collagen proteins and bone morphogenetic protein. Osteocytes, which are associated with collagens, are embedded in the mineralized matrix. Hydroxyapatites, osteocalcin, and osteoaderin are fixed on collagens. In the mineralized intercellular

Rice. 5.2.Participation of various proteins in the formation of the bone tissue matrix.

Table 5.1

Non-collagenous bone proteins

In the matrix, osteoaderin binds to osteonectin, and osteocalcin binds to collagen. Bone morphogenetic protein is located in the border zone between the mineralized and non-mineralized matrix. Osteopontin regulates the activity of osteoclasts.

The properties and functions of bone tissue proteins are presented in table. 5.1.

5.2. PHYSIOLOGICAL BONE TISSUE REGENERATION

In the process of life, the bone is constantly renewed, that is, destroyed and restored. At the same time, two oppositely directed processes occur in it - resorption and restoration. The relationship between these processes is called bone remodeling.

It is known that every 30 years bone tissue changes almost completely. Normally, bone “grows” until the age of 20, reaching peak bone mass. During this period, bone mass increases up to 8% per year. Then, until the age of 30-35, there is a period of more or less stable state. Then a natural gradual decrease in bone mass begins, usually amounting to no more than 0.3-0.5% per year. After menopause, women experience a maximum rate of bone loss, which reaches 2-5% per year and continues at this rate until 60-70 years. As a result, women lose from 30 to 50% of bone tissue. In men, these losses are usually 15-30%.

The process of bone tissue remodeling occurs in several stages (Fig. 5.3). At the first stage, the area of ​​bone tissue to be

Rice. 5.3.Stages of bone tissue remodeling [according to Martin R.B., 2000, as modified].

Resorption pressure is triggered by osteocytes. To activate the process, the participation of parathyroid hormone, insulin-like growth factor, interleukins-1 and -6, prostaglandins, calcitriol, and tumor necrosis factor is necessary. This stage of remodeling is inhibited by estrogen. At this stage, the superficial contour cells change their shape, turning from flat round cells to cubic ones.

Osteoblasts and T lymphocytes secrete receptor activator of nucleation factor kappa B (RANKL) ligands, and up to a certain point, RANKL molecules may remain associated with the surface of osteoblasts or stromal cells.

Osteoclast precursors are formed from bone marrow stem cells. They have membrane receptors called nucleation factor kappa B (RANK) receptors. At the next stage, RANK ligands (RANKL) bind to RANK receptors, which is accompanied by the fusion of several osteoclast precursors into one large structure and mature multinucleated osteoclasts are formed.

The resulting active osteoclast creates a corrugated edge on its surface and mature osteoclasts begin to resorb

bone tissue (Fig. 5.4). On the side where the osteoclast adheres to the destroyed surface, two zones are distinguished. The first zone is the most extensive, called the brush border, or corrugated edge. The corrugated edge is a spirally twisted membrane with multiple cytoplasmic folds that face the direction of resorption on the bone surface. Lysosomes containing a large number of hydrolytic enzymes (cathepsins K, D, B, acid phosphatase, esterase, glycosidases, etc.) are released through the osteoclast membrane. In turn, cathepsin K activates matrix metalloproteinase-9, which is involved in the degradation of collagen and proteoglycans of the intercellular matrix. During this period, carbonic anhydrase activity increases in osteoclasts. HCO 3 - ions are exchanged for Cl -, which accumulate in the corrugated edge; H + ions are also transferred there. Secretion of H + is carried out due to the very active H + /K + -ATPase in osteoclasts. Developing acidosis promotes the activation of lysosomal enzymes and contributes to the destruction of the mineral component.

The second zone surrounds the first and, as it were, seals the area of ​​action of hydrolytic enzymes. It is free from organelles and called

Rice. 5.4.Activation of the preosteoclast RANKL and the formation of a corrugated border by active osteoblasts, leading to bone resorption [according to Edwards P. A., 2005, as amended].

is a clear zone, so bone resorption occurs only under the corrugated edge in a confined space.

At the stage of formation of osteoclasts from precursors, the process can be blocked by the protein osteoprotegerin, which, freely moving, is able to bind RANKL and thus prevent the interaction of RANKL with RANK receptors (see Fig. 5.4). Osteoprotegerin - glycoprotein with mol. weighing 60-120 kDa, belonging to the TNF receptor family. By inhibiting the binding of RANK to the RANK ligand, osteoprotegerin thereby inhibits the mobilization, proliferation and activation of osteoclasts, so an increase in RANKL synthesis leads to bone resorption and, consequently, bone loss.

The nature of bone tissue remodeling is largely determined by the balance between the production of RANKL and osteoprotegerin. Undifferentiated bone marrow stromal cells synthesize RANKL to a greater extent and osteoprotegerin to a lesser extent. The resulting imbalance of the RANKL/osteoprotegerin system with an increase in RANKL leads to bone resorption. This phenomenon is observed in postmenopausal osteoporosis, Paget's disease, bone loss due to cancer metastases and rheumatoid arthritis.

Mature osteoclasts begin to actively absorb bone, and macrophages complete the destruction of the organic matrix of the intercellular substance of the bone. Resorption lasts about two weeks. Then the osteoclasts die in accordance with the genetic program. Osteoclast apoptosis may be delayed by estrogen deficiency. At the last stage, pluripotent stem cells arrive in the destruction zone and differentiate into osteoblasts. Subsequently, osteoblasts synthesize and mineralize the matrix in accordance with new conditions of static and dynamic load on the bone.

There are a large number of factors that stimulate the development and function of osteoblasts (Fig. 5.5). The involvement of osteoblasts in the process of bone remodeling is stimulated by various growth factors - TGF-3, bone morphogenetic protein, insulin-like growth factor, fibroblast growth factor, platelets, colony-stimulating hormones - parathyrin, calcitriol, as well as nuclear binding factor α-1 and is inhibited by the protein leptin Leptin is a protein with a molecular weight of 16 kDa that is formed primarily in adipocytes; it acts through increased synthesis of cytokines, epithelial and keratinocyte growth factors.

Rice. 5.5.Bone tissue remodeling.

Active secreting osteoblasts create layers of osteoid, the unmineralized bone matrix, and slowly replenish the resorption cavity. At the same time, they secrete not only various growth factors, but also proteins of the intercellular matrix - osteopontin, osteocalcin and others. When the resulting osteoid reaches a diameter of 6×10 -6 m, it begins to mineralize. The speed of the mineralization process depends on the content of calcium, phosphorus and a number of trace elements. The mineralization process is controlled by osteoblasts and inhibited by pyrophosphate.

The formation of bone mineral crystals is induced by collagen. The formation of the mineral crystal lattice begins in the zone located between the collagen fibrils. These in turn then become centers for deposition in the spaces between the collagen fibers (Fig. 5.6).

Bone formation occurs only in the immediate vicinity of osteoblasts, with mineralization beginning in cartilage,

Rice. 5.6.Deposition of hydroxyapatite crystals on collagen fibers.

which consists of collagen located in a proteoglycan matrix. Proteoglycans increase the extensibility of the collagen network. In the calcification zone, protein-polysaccharide complexes are destroyed as a result of hydrolysis of the protein matrix by lysosomal enzymes of bone cells. As the crystals grow, they displace not only proteoglycans, but also water. Dense, fully mineralized bone, practically dehydrated; collagen makes up 20% of the mass and 40% of the volume of such tissue; the rest is the share of the mineral part.

The onset of mineralization is characterized by increased absorption of O 2 molecules by osteoblasts, activation of redox processes and oxidative phosphorylation. Ca 2+ and PO 4 3- ions accumulate in mitochondria.

The synthesis of collagen and non-collagen proteins begins, which are then secreted from the cell after post-translational modification. Various vesicles are formed, which contain collagen, proteoglycans and glycoproteins. Special formations called matrix vesicles or membrane vesicles bud from osteoblasts. They contain a high concentration of Ca 2+ ions, which is 25-50 times higher than their content in osteoblasts, as well as glycerophospholipids and enzymes - alkaline phosphatase, pyrophosphatase,

At the same time, partial destruction of proteoglycans associated with type I collagen occurs. The released proteoglycan fragments, negatively charged, begin to bind Ca 2+ ions. A certain number of Ca 2+ and PO 4 3 ions form pairs and triplets that bind to collagen and non-collagen proteins that form the matrix, which is accompanied by the formation of clusters, or nuclei. Of the bone tissue proteins, osteonectin and matrix Gla proteins most actively bind Ca 2+ and PO 4 3 ions. Bone tissue collagen binds PO 4 3 ions through the ε-amino group of lysine to form a phosphoamide bond.

Spiral-shaped structures appear on the formed nucleus, the growth of which proceeds according to the usual principle of adding new ions. The pitch of such a spiral is equal to the height of one structural unit of the crystal. The formation of one crystal leads to the appearance of other crystals; this process is called epitaxy, or epitaxial nucleation.

Crystal growth is highly sensitive to the presence of other ions and molecules that inhibit crystallization. The concentration of these molecules can be small, and they affect not only the rate, but the shape and direction of crystal growth. It is assumed that such compounds are adsorbed on the surface of the crystal and inhibit the adsorption of other ions. Such substances are, for example, sodium hexametaphosphate, which inhibits the precipitation of calcium carbonate. Pyrophosphates, polyphosphates and polyphosphonates also inhibit the growth of hydroxyapatite crystals.

After a few months, after the resorption cavity is filled with bone tissue, the density of the new bone increases. Osteoblasts begin to transform into contour cells that are involved in the continuous removal of calcium from the bone. Some

Osteoblasts transform into osteocytes. Osteocytes remain in the bone; they are connected to each other by long cellular processes and are able to perceive mechanical forces on the bone.

As cells differentiate and age, the nature and intensity of metabolic processes changes. With age, the amount of glycogen decreases by 2-3 times; The released glucose in young cells is 60% used in anaerobic glycolysis reactions, and in old cells it is 85%. Synthesized ATP molecules are necessary for the life support and mineralization of bone cells. Only traces of glycogen remain in osteocytes, and the main supplier of ATP molecules is only glycolysis, due to which the constancy of the organic and mineral composition in the already mineralized sections of bone tissue is maintained.

5.3. REGULATION OF METABOLISM IN BONE TISSUE

Bone tissue remodeling is regulated by systemic (hormones) and local factors that ensure the interaction between osteoblasts and osteoclasts (Table 5.2).

System factors

Bone formation depends to a certain extent on the number and activity of osteoblasts. The process of osteoblast formation is influenced by

Table 5.2

Factors regulating bone remodeling processes

somatotropin (growth hormone), estrogens, 24,25(OH) 2 D 3, which stimulate the division of osteoblasts and the transformation of preosteoblasts into osteoblasts. Glucocorticoids, on the contrary, suppress the division of osteoblasts.

Parathyrin (parathyroid hormone) synthesized in the parathyroid glands. The parathyrin molecule consists of one polypeptide chain containing 84 amino acid residues. The synthesis of parathyrin is stimulated by adrenaline, therefore, under conditions of acute and chronic stress, the amount of this hormone increases. Parathyrins activate the proliferation of osteoblast precursor cells, prolong their half-life and inhibit osteoblast apoptosis. In bone tissue, receptors for parathyrin are present in the membranes of osteoblasts and osteocytes. Osteoclasts lack receptors for this hormone. The hormone binds to osteoblast receptors and activates adenylate cyclase, which is accompanied by an increase in the amount of 3 " 5" cAMP. This increase in cAMP content promotes an intensive supply of Ca 2+ ions from the extracellular fluid. The incoming calcium forms a complex with calmodulin, and then calcium-dependent protein kinase is activated, followed by protein phosphorylation. By binding to osteoblasts, parathyrin causes the synthesis of osteoclast-activating factor - RANKL, which can bind to preosteoclasts.

The administration of large doses of parathyrin leads to the death of osteoblasts and osteocytes, which is accompanied by an increase in the resorption zone, an increase in the level of calcium and phosphate in the blood and urine, with a simultaneous increase in the excretion of hydroxyproline due to the destruction of collagen proteins.

Receptors for parathyrin are also located in the renal tubules. In the proximal renal tubules, the hormone inhibits the reabsorption of phosphate and stimulates the formation of 1,25(OH) 2 D 3. In the distal parts of the renal tubules, parathyrin enhances the reabsorption of Ca 2+. Thus, parathyrin ensures an increase in calcium levels and a decrease in phosphates in the blood plasma.

Parotin -a glycoprotein secreted by the parotid and submandibular salivary glands. Protein consists of α-, β -, and γ-subunits. The active principle of parotin is the γ-subunit, which affects mesenchymal tissues - cartilage, tubular bones, tooth dentin. Parotin enhances the proliferation of chondrogenic cells, stimulates the synthesis of nucleic acids and DNA in odontoblasts, pro-

mineralization processes of dentin and bones. These processes are accompanied by a decrease in calcium and glucose levels in the blood plasma.

Calcitonin- a polypeptide consisting of 32 amino acid residues. Secreted by parafollicular K cells of the thyroid gland or C cells of the parathyroid glands as a high molecular weight precursor protein. Calcitonin secretion increases with increasing concentration of Ca 2+ ions and decreases with decreasing concentration of Ca 2+ ions in the blood. It also depends on estrogen levels. With a lack of estrogen, the secretion of calcitonin decreases. This causes increased calcium mobilization in bone tissue and contributes to the development of osteoporosis.

Thus, calcitonin suppresses the activity of osteoclasts and inhibits the release of Ca 2+ ions from bone tissue, and also reduces the reabsorption of Ca 2+ ions in the kidneys. As a result, bone tissue resorption is inhibited and mineralization processes are stimulated, which is manifested by a decrease in the level of calcium and phosphorus in the blood plasma.

Iodine-containing hormones thyroid gland - thyroxine (T4) and triiodothyronine (T3) ensure optimal bone growth. Thyroid hormones can stimulate the secretion of growth hormones. They increase both the synthesis of insulin-like growth factor 1 (IGF-1) mRNA and the production of IGF-1 itself in the liver. In hyperthyroidism, the differentiation of osteogenic cells and protein synthesis in these cells are suppressed, and the activity of alkaline phosphatase is reduced. Due to the increased secretion of osteocalcin, osteoclast chemotaxis is activated, which leads to bone resorption.

Sex steroids hormones are involved in the processes of bone tissue remodeling. The effect of estrogens on bone tissue is manifested in the activation of osteoblasts (direct and indirect effects), inhibition of osteoclasts. They also promote the absorption of Ca 2+ ions in the gastrointestinal tract and its deposition in bone tissue.

Female sex hormones stimulate the production of calcitonin by the thyroid gland and reduce the sensitivity of bone tissue to parathyrin. They also competitively displace corticosteroids from their receptors in bone tissue. Androgens, having an anabolic effect on bone tissue, stimulate protein biosynthesis in osteoblasts, and are also aromatized in adipose tissue into estrogens.

In conditions of deficiency of sex steroids, which occurs in menopause, the processes of bone resorption begin to prevail over the processes of bone tissue remodeling, which leads to the development of osteopenia and osteoporosis.

Glucocorticoids synthesized in the adrenal cortex. The main glucocorticoid in humans is cortisol. Glucocorticoids act in a coordinated manner on different tissues and different processes - both anabolic and catabolic. In bone tissue, cortisol inhibits the synthesis of type I collagen, some non-collagen proteins, proteoglycans and osteopontin. Glucocorticoids also reduce the number of mast cells, which are the site of hyaluronic acid production. Under the influence of glucocorticoids, protein breakdown accelerates. Glucocorticoids suppress the absorption of Ca 2+ ions in the intestine, which is accompanied by a decrease in it in the blood serum. This decrease results in the release of parathyrin, which stimulates osteoclast formation and bone resorption (Fig. 5.7). In addition, cortisol in muscles and bones stimulates the breakdown of proteins, which also impairs bone formation. Ultimately, the actions of glucocorticoids lead to bone loss.

Vitamin D 3 (cholecalciferol) comes from food, and is also formed from the precursor 7-dehydrocholesterol under the influence of ultraviolet rays. In the liver, cholecalciferol is converted into 25(OH)D3, and in the kidneys further hydroxylation of 25(OH)D3 occurs and 2 hydroxylated metabolites are formed - 1,25(OH)2D3 and 24,25(OH)2D3. Metabolites of vitamin D 3 regulate chondrogenesis and osteogenesis already during embryonic development. In the absence of vitamin D 3, the mineralization of the organic matrix is ​​impossible, the vascular network is not formed, and the metaphyseal bone is not able to form properly. 1,25(OH) 2 D 3 binds to chondroblasts in an active state, and 24,25(OH) 2 D 3 binds to cells in a resting state. 1,25(OH) 2 D 3 regulates growth zones through the formation of a complex with the nuclear receptor for this vitamin. It has also been shown that 1,25(OH) 2 D 3 is capable of bonding

Rice. 5.7.Scheme of the influence of glucocorticoids on metabolic processes leading to bone loss

interact with the membrane-nuclear receptor, which leads to the activation of phospholipase C and the formation of inositol-3-phosphate. In addition, the resulting complex is activated by phospholipase A 2 . Prostaglandin E2 is synthesized from the released arachidonic acid, which also affects the response of chondroblasts when they bind to 1,25(OH)2D3. In contrast, after 24,25(OH)2D3 binds to its membrane-binding receptor, phospholipase C and then protein kinase C are activated.

In the cartilaginous growth zone of the epiphyses of bone tissue, 24,25(OH) 2 D 3 stimulates the differentiation and proliferation of prechondroblasts, which contain specific receptors for this metabolite. Metabolites of vitamin D 3 influence the formation and functional state of the temporomandibular joint.

Vitamin A.

With a deficiency or excess intake of vitamin A into the body of children, bone growth is disrupted and their deformation occurs. These phenomena are probably due to the depolymerization and hydrolysis of chondroitin sulfate, which is part of the cartilage.Vitamin C

.With a lack of ascorbic acid in mesenchymal cells, hydroxylation of lysine and proline residues does not occur, which leads to disruption of the formation of mature collagen. The resulting immature collagen is not able to bind Ca 2+ ions and thus the mineralization processes are disrupted.

Vitamin E

. With vitamin E deficiency, the liver does not produce 25(OH)D3, a precursor to active forms of vitamin D3. Vitamin E deficiency can also lead to low levels of magnesium in bone tissue.Local factors

Prostaglandinsaccelerate the release of Ca 2+ ions from the bone. Exogenous prostaglandins increase the generation of osteoclasts, which destroy bone. They have a catabolic effect on protein metabolism in bone tissue and inhibit their synthesis.

Lactoferrin- iron-containing glycoprotein, in physiological concentrations stimulates the proliferation and differentiation of osteoblasts, and also inhibits osteoclastogenesis. The mitogenic effect of lactoferrin on osteoblast-like cells occurs through specific receptors.

The resulting complex enters the cell through endocytosis, and lactoferrin phosphorylates mitogen-activating protein kinases. Thus, lactoferrin acts as a factor in bone growth and bone health. Can be used as an anabolic factor in osteoporosis.(Cytokines) - proteins (from IL-1 to IL-18), synthesized mainly by T-cells of lymphocytes, as well as mononuclear phagocytes. The functions of IL are associated with the activity of other physiologically active peptides and hormones. At physiological concentrations, they inhibit cell growth, differentiation and lifespan. They reduce the production of collagenase, the adhesion of endothelial cells to neutrophils and eosinophils, the production of NO and, as a result, there is a decrease in the degradation of cartilage tissue and bone resorption.

The process of bone tissue resorption can be activated by acidosis and large amounts of integrins, IL and vitamin A, but is inhibited by estrogens, calcitonin, interferon and bone morphogenetic protein.

Bone turnover markers

Biochemical markers provide information about the pathogenesis of skeletal diseases and the phases of bone tissue remodeling. There are biochemical markers of bone formation and resorption that characterize the functions of osteoblasts and osteoclasts.

Prognostic significance of determining markers of bone tissue metabolism:

Screening using these markers allows us to identify patients at high risk of developing osteoporosis; high levels of bone resorption markers may be associated with

increased risk of fractures; an increase in the level of bone turnover markers in patients with osteoporosis by more than 3 times compared to normal values ​​suggests another bone pathology, including malignant; Resorption markers can be used as additional criteria when deciding whether to prescribe special therapy for the treatment of bone pathology. Bone resorption markers

Collagen breakdown is the only source of free hydroxyproline in the body. The predominant part of hydroxyproline

is catabolized, and some is excreted in the urine, mainly in the composition of small peptides (di- and tripeptides). Therefore, the content of hydroxyproline in the blood and urine reflects the balance of the rate of collagen catabolism. In an adult, 15-50 mg of hydroxyproline is excreted per day, in a young age up to 200 mg, and in some diseases associated with collagen damage, for example: hyperparathyroidism, Paget's disease and hereditary hyperhydroxyprolinemia, which is caused by a defect in the enzyme hydroxyproline oxidase, the amount in the blood and hydroxyproline excreted in urine increases.

Osteoclasts secrete tartrate-resistant acid phosphatase. As osteoclast activity increases, the content of tartrate-resistant acid phosphatase increases and it enters the bloodstream in increased quantities. In the blood plasma, the activity of this enzyme increases in Paget's disease and cancer with metastases to the bone. Determination of the activity of this enzyme is especially useful in monitoring the treatment of osteoporosis and oncological diseases accompanied by damage to bone tissue.

Bone formation markers .

Bone formation is assessed by the amount of osteocalcin, bone isoenzyme alkaline phosphatase and osteoprotegerin. Measuring the amount of serum osteocalcin allows us to determine the risk of developing osteoporosis in women, monitor bone metabolism during menopause and hormone replacement therapy. Rickets in young children is accompanied by a decrease in the content of osteocalcin in the blood, and the degree of decrease in its concentration depends on the severity of the rickets process. In patients with hypercortisolism and patients receiving prednisolone, the content of osteocalcin in the blood is significantly reduced, which reflects the suppression of bone formation processes.

The alkaline phosphatase isoenzyme is present on the cell surface of osteoblasts. With increased synthesis of the enzyme by bone tissue cells, its amount in the blood plasma increases, therefore, determining the activity of alkaline phosphatase, especially the bone isoenzyme, is an informative indicator of bone remodeling.

Osteoprotegerin acts as a TNF receptor. By binding to preosteoclasts, it inhibits the mobilization, proliferation and activation of osteoclasts.

5.4. REACTION OF BONE TISSUE TO DENTAL

For various forms of edentia, an alternative to removable prosthetics are intraosseous dental implants. The reaction of bone tissue to an implant can be considered a special case of reparative regeneration.

There are three types of connection between dental implants and bone tissue:

Direct engraftment - osseointegration;

Fibrous-osseous integration, when a layer of fibrous tissue about 100 microns thick is formed around the dental implant;

Periodontal junction (the rarest type), formed in the case of periodontal ligament-like fusion with peri-implantation collagen fibers or (in some cases) cementation of an intraosseous dental implant.

It is believed that during the process of osseointegration after the placement of dental implants, a thin zone of proteoglycans is formed, which is devoid of collagen. The bonding area of ​​the dental implant to the bone is provided by a double layer of proteoglycans, including decorin molecules.

With fibroosseous integration, numerous components of the extracellular matrix are also involved in the connection of the implant with the bone tissue. Type I and III collagens are responsible for the stability of the implant in its capsule, and fibronectin plays a major role in binding connective tissue elements to the implants.

However, after a certain period of time, under the influence of mechanical load, the activity of collagenase, cathepsin K and acid phosphatase increases. This leads to loss of bone tissue in the peri-implantation area and disintegration of the dental implant occurs. Early disintegration of intraosseous dental implants occurs against the background of a reduced amount of fibronectin, Gla protein, and tissue inhibitor of matrix metalloproteinases (TIMP-1) in the bone.

Each human bone is a complex organ: it occupies a certain position in the body, has its own shape and structure, and performs its own function. All types of tissues take part in bone formation, but bone tissue predominates.

General characteristics of human bones

Cartilage covers only the articular surfaces of the bone, the outside of the bone is covered with periosteum, and the bone marrow is located inside. Bone contains fatty tissue, blood and lymphatic vessels, and nerves.

Bone has high mechanical qualities, its strength can be compared with the strength of metal. The chemical composition of living human bone contains: 50% water, 12.5% ​​organic substances of a protein nature (ossein), 21.8% inorganic substances (mainly calcium phosphate) and 15.7% fat.

Types of bones by shape divided into:

• Tubular (long - humeral, femoral, etc.; short - phalanges of the fingers);
• flat (frontal, parietal, scapula, etc.);
• spongy (ribs, vertebrae);
• mixed (sphenoid, zygomatic, lower jaw).

The structure of human bones

The basic structure of the unit of bone tissue is osteon, which is visible through a microscope at low magnification. Each osteon includes from 5 to 20 concentrically located bone plates. They resemble cylinders inserted into each other. Each plate consists of intercellular substance and cells (osteoblasts, osteocytes, osteoclasts). In the center of the osteon there is a canal - the osteon canal; vessels pass through it. Intercalated bone plates are located between adjacent osteons.

Bone tissue is formed by osteoblasts, secreting the intercellular substance and immuring itself in it, they turn into osteocytes - process-shaped cells, incapable of mitosis, with poorly defined organelles. Accordingly, the formed bone contains mainly osteocytes, and osteoblasts are found only in areas of growth and regeneration of bone tissue.

The largest number of osteoblasts are located in the periosteum - a thin but dense connective tissue plate containing many blood vessels, nerve and lymphatic endings. The periosteum ensures bone growth in thickness and nutrition of the bone.

Osteoclasts contain a large number of lysosomes and are capable of secreting enzymes, which can explain their dissolution of bone matter. These cells take part in the destruction of bone. In pathological conditions in bone tissue, their number increases sharply.

Osteoclasts are also important in the process of bone development: in the process of building the final shape of the bone, they destroy calcified cartilage and even newly formed bone, “correcting” its primary shape.

Bone structure: compact and spongy

On cuts and sections of bone, two of its structures are distinguished - compact substance(bone plates are located densely and orderly), located superficially, and spongy substance(bone elements are loosely located), lying inside the bone.

This bone structure fully complies with the basic principle of structural mechanics - to ensure maximum strength of the structure with the least amount of material and great lightness. This is also confirmed by the fact that the location of the tubular systems and the main bone beams corresponds to the direction of action of the compressive, tensile and torsional forces.

Bone structure is a dynamic reactive system that changes throughout a person's life. It is known that in people engaged in heavy physical labor, the compact layer of bone reaches a relatively large development. Depending on changes in the load on individual parts of the body, the location of the bone beams and the structure of the bone as a whole may change.

Connection of human bones

All bone connections can be divided into two groups:

• Continuous connections, earlier in development in phylogeny, immobile or sedentary in function;
• discontinuous connections, later in development and more mobile in function.

There is a transition between these forms - from continuous to discontinuous or vice versa - semi-joint.

The continuous connection of bones is carried out through connective tissue, cartilage and bone tissue (the bones of the skull itself). A discontinuous bone connection, or joint, is a younger formation of a bone connection. All joints have a general structural plan, including the articular cavity, articular capsule and articular surfaces.

Articular cavity stands out conditionally, since normally there is no void between the articular capsule and the articular ends of the bones, but there is liquid.

Bursa covers the articular surfaces of the bones, forming a hermetic capsule. The joint capsule consists of two layers, the outer layer of which passes into the periosteum. The inner layer releases fluid into the joint cavity, which acts as a lubricant, ensuring free sliding of the articular surfaces.

Types of joints

The articular surfaces of articulating bones are covered with articular cartilage. The smooth surface of articular cartilage promotes movement in the joints. Articular surfaces are very diverse in shape and size; they are usually compared to geometric figures. Hence name of joints based on shape: spherical (humeral), ellipsoidal (radio-carpal), cylindrical (radio-ulnar), etc.

Since the movements of the articulated links occur around one, two or many axes, joints are also usually divided according to the number of axes of rotation into multiaxial (spherical), biaxial (ellipsoidal, saddle-shaped) and uniaxial (cylindrical, block-shaped).

Depending on the number of articulating bones joints are divided into simple, in which two bones are connected, and complex, in which more than two bones are articulated.

Bone tissue is an amazing unity of a protein base and a mineral substrate, mutually penetrating each other. The protein base of bone is 30%, mineral substance – 60%, water – 10%. The mineral component of bone tissue contains from 1050 to 1200 g of calcium, from 450 to 500 g of phosphorus, from 5 to 8 g of magnesium. Bone tissue contains calcium phosphate 85%, calcium carbonate 10%, magnesium phosphate 1.5%, calcium fluoride 0.3%, various trace elements 0.001%. These microelements include chlorine, aluminum, boron, fluorine, copper, manganese, silver, lead, strontium, barium, cadmium, cobalt, iron, zinc, titanium, silicon and others. Microelements play a decisive role in the vegetative processes occurring in bone tissue. For example, copper activates enzymes produced by osteoblasts, manganese accelerates the activity of alkaline phosphatase, and zinc promotes the functioning of oxidation enzymes.

Bone tissue is a special type of connective tissue, also consisting of cells and intercellular substance. Bone cells include osteoblasts, osteocytes, and osteoclasts. Unlike other types of connective tissue, bone is characterized by a significant content of intercellular substance and its unique structure. The intercellular substance (bone matrix) consists of a large number of collagen fibers (bone collagen - ossein), surrounded by an amorphous substance (osseomucoid). Osseomucoid contains glycoproteins, mucopolysaccharides and a large amount of calcium salts. Bone tissue, due to its strength, serves as a support in the body and at the same time represents a depot of mineral salts.

Osteogenic cells are mesenchymal in nature and are formed from pluripotent cells, which are both a source of cartilage and bone tissue.

Basically, cartilage in the body develops during intrauterine development and exists temporarily, later being replaced by bone. While a person grows, cartilaginous growth zones remain and function. Hyaline cartilage, which covers the ends of the bones that form the joints, plays a huge role in the function of the musculoskeletal system. Cartilage tissue can be found in the wall of the trachea, larynx, nose, and in places where the ribs are attached to the sternum.

Osteoblasts formed as a result of differentiation of mesenchymal cells are responsible for the synthesis of new bone. One of the morphological features of these cells is the presence of long cytoplasmic processes. Osteoblasts synthesize an organic matrix that gradually surrounds the cells, as if bricking them up. As a result of this process, so-called lacunae are formed containing bone cells, which are now called osteocytes. Thanks to processes, cells connect to each other. Surrounded by a bone matrix and interconnected, the cytoplasmic processes form a system of bone tubules. Osteoclasts are a group of cells responsible for bone resorption.

Osteogenic cells are located on the bone surface in two layers: 1) periosteum, which covers the outer surface of the bone and 2) endosteum, which lines the internal surfaces of all bone cavities. The periosteum, in turn, has two layers: 1) outer fibrous and 2) inner osteogenic. It is the deep layer of periosteum that takes an active part in osteogenesis. The periosteum contains blood vessels that enter and exit the bone.

During the process of development and growth, bone tissue undergoes certain morphological changes. There are two types of bone tissue: immature (coarse-fiber) and mature (lamellar) bone tissue. Immature bone usually occurs in the human body during embryogenesis, as well as in the early stages of callus formation after a fracture. Immature bone is characterized by a larger number of cells. The intercellular substance contains more proteoglycans, glycoproteins and calcium. The arrangement of fibers in the bone matrix resembles a mesh. Hence the second name for this type of bone is reticular. Bone growth in length occurs due to epiphyseal cartilaginous growth plates. The thickness of the bone increases as a result of gradual appositional growth of bone tissue from the outside and resorption of the internal part of the bone substance.

After birth, immature bone tissue is gradually replaced by mature bone tissue, which is already represented by two types: spongy and compact. The carpal and tarsal bones, vertebral bodies, and metaphyses of long tubular bones are made of spongy tissue. The diaphyses of tubular bones are formed from compact bone tissue.

The process of bone tissue formation takes place near small vessels, since bone tissue cells need nutrition. The formation of bone tissue begins with the formation of bone trabeculae, the so-called bone columns. Bone trabeculae consist of osteoblasts, which are located along the periphery; in the center there is the intercellular substance of the bone, in some areas of which osteocytes can be observed. Gradually developing, the trabeculae interconnect and form a branched network. This anastomosing network of bony trabeculae is called cancellous bone. A characteristic feature of this type of bone tissue is also the presence of cavities located between the trabeculae, filled with connective tissue and blood vessels.

Compact bone is characterized by the presence of mainly bone tissue. The structural unit of compact bone is the osteon or Haversian system (named after Havers, who first described it). An osteon is a collection of osteocytes and organic matrix interconnected by bone tubules that surround one or two small vessels. The channel containing the capillary in the center of the osteon is also called Haversian. The osteon dimensions generally do not exceed 0.4 mm. Osteocytes of compact bone are located concentrically with respect to the capillary, which facilitates the unimpeded flow of tissue fluid to them from the blood vessel that provides their nutrition. The diameter of the osteon is limited by the distance at which the bone tubule systems are capable of operating. The distance from the cells to the central blood vessels usually does not exceed 0.1-0.2 mm. And the number of concentric plates surrounding the Haversian canal does not exceed five or six. The spaces between the Haversian systems are filled with interstitial bone plates, which is why the surface of compact bone is smooth and not lumpy.

The vascular network of bone tissue is a complex system that is in close connection with the circulatory system of the surrounding soft tissues. The blood supply to the bone comes from three sources: 1) feeding arteries and veins; 2) vessels of the metaphysis; 3) vessels of the periosteum. Two to three feeding arteries penetrate the bone at the level of the upper and middle thirds of the diaphysis through the so-called feeding foramina and form a medullary blood network. The exception is the tibia, which has only one artery, which enters the diaphysis at the level of its upper third. The feeding arteries branch along the Haversian canal system and account for almost 50% of the bone mass. The vessels of the metaphysis take part in the blood supply to the epimetaphyses of the tubular bones. The vessels of the periosteum penetrate the bone through the so-called bone canals of Volkmann and anastomose with the vessels of the Haversian systems. It has been experimentally proven that the vessels of the periosteum play a large role in the complete venous outflow from the bone, since the feeding vein, which is much thinner than the artery, could not cope with this task on its own. It is now generally accepted that the nutrient arteries primarily take part in the blood supply to the inner two-thirds of the cortical layer, and the outer third is additionally supplied with blood by the vessels of the periosteum.

Throughout life, from the beginning of embryogenesis to the death of the organism, bone tissue constantly undergoes restructuring. In the beginning, it is associated with the growth and development of the body. After the end of growth, constant internal restructuring continues, which consists of the gradual resorption of part of the bone substance and its replacement with new bone. This is explained by the fact that the Haversian systems of compact bone and trabeculae of cancellous bone are not preserved throughout life. Bone tissue, like many other tissues in the human body, must be constantly renewed all the time. 2-4% of bone tissue is renewed annually. Until 20-30 years of age, intensive accumulation of bone tissue occurs. From 30 to 40 years, a period of equilibrium begins between the processes of resorption and restoration. After 40 years, bone mineral density gradually decreases.

The structure of bone tissue. Bones consist of lamellar bone tissue, which is classified as connective tissue. The basis is made up of three types of cells: osteoblasts (forming bone tissue), osteoclates (destroying bone tissue) and osteocytes (participating in the mineralization of bone tissue). The cells are located in the intercellular substance (30% organic and 70% inorganic substances), which together form bone plates.

The structure of bone as an organ. Bone has a complex structure and chemical composition. In a living organism, bone contains 50% water, 28.15% organic substances, including 15.75% fat, and 21.85% inorganic substances (compounds of calcium, phosphorus, magnesium, etc.).

Bone strength (mechanical properties) is ensured by the physicochemical unity of organic and inorganic substances, as well as the structure of bone tissue. The predominance of organic substances in the bone (in children) provides it with greater firmness and elasticity. When the ratio changes towards the predominance of inorganic substances, the bone becomes brittle and brittle (in old people).

Each bone is an independent organ and consists of bone tissue. Outside the bone is covered with periosteum, inside it in the medullary cavities , there is bone marrow (Fig. 1.2).

Rice. 1.2. Bone structure.

In addition to the articular surfaces covered with cartilage, the outside of the bone is covered periosteum. It can be divided into two layers: outer (fibrous) and inner (osteogenic, bone-forming). Due to the inner layer of the periosteum, osteoblasts are formed and the bone grows in thickness.

The outer layer of bone is represented by a thick (in the diaphyses of tubular bones) or thin (in the epiphyses of tubular bones, in spongy and flat bones) plate of compact substance. Under the compact substance there is a spongy (trabecular) substance, porous, built from bone beams with cells between them (Fig. 1.2).

Inside the diaphysis of the long bones there is a medullary cavity containing bone marrow.

The central canal with a system of concentric plates is a structural unit of bone and is called osteona, or Haversian system(Fig. 1.2). The spaces between the osteons are made of intercalary (intermediate) plates. Osteons and intercalated plates form a compact cortical bone.

Inside the bone, in the bone marrow cavity and cells of the spongy substance, there is Bone marrow. In the prenatal period and in newborns, all bones contain red bone marrow, performing hematopoietic and protective functions. It is represented by a network of reticular fibers and cells. The loops of this network contain young and mature blood cells and lymphoid elements. Nerve fibers and blood vessels branch in the bone marrow. In an adult, red bone marrow is contained only in the cells of the spongy substance of flat bones (skull bones, sternum, wings of the ilium), in spongy (short) bones, and the epiphyses of long bones. In the medullary cavity of the diaphysis of tubular bones there is yellow bone marrow representing a degenerated reticular stroma with fatty inclusions.

There are irregularities on the surface of each bone: this is where muscles and their tendons, fascia, and ligaments begin or attach. These elevations protruding above the surface of the bone are called apophyses (tubercle, tubercle, ridge, process). In the area where the muscle is attached with its fleshy part, depressions (pit, fossa, dimple) are determined.