Bone cavity. Structure and composition of bones. Age-related changes in bones

66367 1

Bone represents a very advanced specialized variety of tissues of the internal environment.

This system harmoniously combines such opposing properties as mechanical strength and functional plasticity, the processes of new formation and destruction.

Bone tissue consists of cells and intercellular substance, which are characterized by a certain histoarchitecture. The main cells of bone tissue are osteoblasts, osteocytes and osteoclasts.

Osteoblasts have an oval or cubic shape. The large light nucleus is not located in the center, it is somewhat shifted to the periphery of the cytoplasm. Often several nucleoli are found in the nucleus, which indicates the high synthetic activity of the cell.

Electron microscopic studies have shown that a significant part of the osteoblast cytoplasm is filled with numerous ribosomes and polysomes, tubules of the granular endoplasmic reticulum, the Golgi complex, mitochondria, and special matrix vesicles. Osteoblasts have proliferative activity, are producers of intercellular substance and play a major role in the mineralization of the bone matrix. They synthesize and secrete chemical compounds such as alkaline phosphatase, collagens, osteonectin, osteopontin, osteocalcin, bone morphogenetic proteins, etc. The matrix vesicles of osteoblasts contain numerous enzymes, which, when released outside the cell, initiate bone mineralization processes.

The organic matrix of bone tissue synthesized by osteoblasts consists predominantly (90-95%) of type I collagen, III-V collagens and other types, as well as non-collagen proteins (osteocalcin, osteopontin, osteonectin, phosphoproteins, bone morphogenetic proteins) and glycosaminoglycan substances. Proteins of a non-collagenous nature have the properties of mineralization regulators, osteoinductive substances, mitogenic factors, and regulators of the rate of formation of collagen fibrils. Thrombospondin promotes the adhesion of osteoblasts to subperiosteal osteoid of human bone. Osteocalcin is considered a potential indicator of the function of these cells.

The ultrastructure of osteoblasts indicates that their functional activity is different. Along with functionally active osteoblasts with high synthetic activity, there are inactive cells. Most often they are localized on the periphery of the bone from the side of the medullary canal and are part of the periosteum. The structure of such cells is characterized by a low content of organelles in the cytoplasm.

Osteocytes are more differentiated cells than osteoblasts. They have a process shape.

Osteocyte processes are located in tubules that penetrate the mineralized bone matrix in various directions. The flattened bodies of osteocytes are located in special cavities - lacunae - and are surrounded on all sides by a mineralized bone matrix. A significant part of the osteocyte cytoplasm is occupied by the ovoid nucleus. Organelles of synthesis in the cytoplasm are poorly developed: there are a few polysomes, short tubules of the endoplasmic reticulum, and single mitochondria. Due to the fact that the tubules of neighboring lacunae anastomose with each other, the processes of osteocytes are interconnected using specialized gap junctions. In a small space around the bodies and processes of osteocytes, tissue fluid circulates, containing a certain concentration of Ca 2+ and PO 4 3-, and may contain unmineralized or partially mineralized collagen fibrils.

The function of osteocytes is to maintain the integrity of the bone matrix by participating in the regulation of bone mineralization and providing a response to mechanical stimuli. Currently, more and more evidence is accumulating that these cells take an active part in the metabolic processes occurring in the intercellular substance of bone, in maintaining the constancy of the ion balance in the body. The functional activity of osteocytes largely depends on the stage of their life cycle and the action of hormonal and cytokine factors.

Osteoclasts- These are large multinucleated cells with strongly oxyphilic cytoplasm. They are part of the body's phagocytic-macrophage system, derivatives of blood monocytes.

A corrugated brush border is defined at the periphery of the cell. The cytoplasm contains many ribosomes and polysomes, mitochondria, endoplasmic reticulum tubules, and the Golgi complex is well developed. A distinctive feature of the ultrastructure of osteoclasts is the presence of a large number of lysosomes, phagosomes, vacuoles and vesicles.

Osteoclasts have the ability to create an acidic environment locally at their surface as a result of intensive glycolysis processes occurring in these cells. The acidic environment in the area of ​​direct contact between the cytoplasm of osteoclasts and the intercellular substance promotes the dissolution of mineral salts and creates optimal conditions for the action of proteolytic and a number of other lysosome enzymes. A cytochemical marker of osteoclasts is the activity of the acid phosphatase isoenzyme, which is called acid nitrophenylphosphatase. The functions of osteoclasts include resorption (destruction) of bone tissue and participation in the process of remodeling bone structures during embryonic and postnatal development.

The intercellular substance of bone tissue consists of organic and inorganic components. Organic compounds are represented by collagens I, III, IV, V, IX, XIII types (about 95%), non-collagen proteins (bone morphogenetic proteins, osteocalcin, osteopontin, thrombospondin, bone sialoprotein, etc.), glycosaminoglycans and proteoglycans. The inorganic part of the bone matrix is ​​represented by hydroxyapatite crystals containing large quantities of calcium and phosphorus ions; in much smaller quantities it contains magnesium and potassium salts, fluorides, and bicarbonates.

The intercellular substance of bone is constantly renewed. The destruction of old intercellular substance is a rather complex and not yet clear in many details process, in which all types of bone tissue cells and a number of humoral factors take part, but osteoclasts play a particularly noticeable and important role.

Types of bone tissue

Depending on the microscopic structure, there are two main types of bone tissue - reticulofibrous (coarse fibrous) and lamellar.

Reticulofibrous bone tissue is widely represented in embryogenesis and early postnatal histogenesis of skeletal bones, and in adults it is found in the places of attachment of tendons to bones, along the line of healing of cranial sutures, as well as in the area of ​​fractures.

Both in embryogenesis and during regeneration, reticulofibrous bone tissue is always replaced by lamellar tissue over time. A characteristic feature of the structure of reticulofibrous bone tissue is the disordered, diffuse arrangement of bone cells in the intercellular substance. Powerful bundles of collagen fibers are weakly mineralized and run in different directions. The density of osteocytes in reticulofibrous bone tissue is higher than in lamellar bone tissue, and they do not have a specific orientation in relation to collagen (ossein) fibers.

Lamellar bone tissue is the main tissue in almost all human bones. In this type of bone tissue, the mineralized intercellular substance forms special bone plates 5-7 microns thick.

Each bone plate is a collection of closely spaced parallel collagen fibers impregnated with hydroxyapatite crystals. In adjacent plates, the fibers are located at different angles, which gives the bone additional strength. Between the bone plates in the lacunae, bone cells - osteocytes - lie in an orderly manner. Osteocyte processes penetrate through bone canaliculi into the surrounding plates, entering into intercellular contacts with other bone cells. There are three systems of bone plates: surrounding (general, there are external and internal), concentric (part of the osteon structure), intercalary (representing the remnants of collapsing osteons).

The composition of bone is divided into compact and spongy substance. Both of them are formed by lamellar bone tissue. Features of the histoarchitectonics of lamellar bone will be presented below when describing bone as an organ.

Joint diseases
IN AND. Mazurov

Chemical components of bone tissue

Bone tissue is classified as a very dense specialized connective tissue and is divided into coarse fibrous and lamellar. Coarse fibrous bone tissue is well represented in embryos, and in adults it is found only in the places of attachment of tendons to bones and overgrown sutures of the skull. Lamellar bone tissue forms the basis of most tubular and flat bones.

Bone tissue performs vital functions in the body:

1. The musculoskeletal function is determined by the biochemical composition of the organic and inorganic phases of bones, their architectonics and movable articulation into a system of levers.

2. The protective function of bones is to form channels and cavities for the brain, spinal and bone marrow, as well as for internal organs (heart, lungs, etc.).

3. The hematopoietic function is based on the fact that the entire bone, and not just the bone marrow, takes part in the mechanisms of hematopoiesis.

4. Deposition of minerals and regulation of mineral metabolism: up to 99% of calcium, over 85% of phosphorus and up to 60% of the body’s magnesium are concentrated in the bones.

5. The buffer function of bone is ensured by its ability to easily give and receive ions in order to stabilize the ionic composition of the internal environment of the body and maintain acid-base balance.

Bone tissue, like other types of connective tissue, consists of cells and extracellular substance. It contains three main types of cells - osteoblasts, osteoclasts and osteocytes. The extracellular substance basically contains an organic matrix structured by a mineral phase. The strong type I collagen fibers in bone are resistant to tension, while the mineral crystals are resistant to compression. When bone is soaked in dilute acid solutions, its mineral components are washed away, leaving behind a flexible, soft, translucent organic component that retains the shape of the bone.

Mineral part of bone

A feature of the chemical composition of bone tissue is the high content of mineral components. Inorganic substances make up only about 1/4-1/3 of the bone volume, and the rest of the volume is occupied by the organic matrix. However, the specific masses of the organic and inorganic components of bone are different, so on average, insoluble minerals account for half of the bone mass, and even more in its dense parts.

The functions of the mineral phase of bone tissue are part of the functions of the entire bone. Mineral components:

1) make up the skeleton of the bone,

2) give shape and hardness to the bone,

3) give strength to protective bone frames for organs and tissues,

4) represent a depot of mineral substances in the body.

The mineral part of bone consists mainly of calcium phosphates. In addition, it includes carbonates, fluorides, hydroxides and citrates. The composition of bones includes most of the Mg 2+, about a quarter of the body's Na + and a small part of K +. Bone crystals consist of hydroxyapatites - Ca 10 (PO 4) 6 (OH) 2. The crystals are in the form of plates or sticks with dimensions of 8-15/20-40/200-400 Ǻ. Due to the characteristics of the inorganic crystalline structure, the elasticity of bone is similar to that of concrete. The detailed characteristics of the mineral phase of bone and the features of mineralization are presented below.

Organic bone matrix

The organic matrix of bone is 90% collagen, the rest is non-collagenous proteins and proteoglycans.

Collagen fibrils of the bone matrix are formed collagen type I, which is also part of tendons and skin. Bone proteoglycans are represented mainly chondroitin sulfate, which is very important for bone metabolism. It forms the basic substance of bone with proteins and is important in Ca 2+ metabolism. Calcium ions bind to the sulfate groups of chondroitin sulfate, which is capable of active ion exchange because it is a polyanion. When it is degraded, the binding of Ca 2+ is disrupted.

Bone-specific matrix proteins

Osteocalcin (molecular weight 5.8 kDa) is present only in bones and teeth, where it is the predominant protein and has been best studied. It is a small (49 amino acid residues) protein structure non-collagenous nature,also called bone glutamine protein or gla protein. For synthesis, osteoblasts require vitamin K (phylloquinone or menaquinone). Three γ-carboxyglutamic acid residues were found in the osteocalcin molecule, which indicates the ability to bind calcium. Indeed, this protein is tightly bound to hydroxyapatite and is involved in the regulation of crystal growth by binding Ca 2+ in bones and teeth. Synthesized include extends into the extracellular space of the bone, butpart of it hitenters the bloodstream, where it can be analyzed. High levels of parathyroid hormone (PTH)inhibits the activity of osteoblasts producing osteocalcin, and reduces its content in bone tissue and blood. The synthesis of osteocalcin is controlled by vitamin D 3, which indicates the connection of the protein with calcium mobilization. Disturbances in the metabolism of this protein cause dysfunction of bone tissue. A number of similar proteins have been isolated from bone tissue and are called “osteocalcin-like proteins.”

Bone sialoprotein (molecular weight 59 kDa) found only in bones. It is characterized by a high content of sialic acids and contains the tripeptide ARG-GLI-ASP, typical of proteins that have the ability to bind to cells and are called “integrins” (integral proteins of plasma membranes that play the role of receptors for proteins of the intercellular matrix). It was later found that the binding of sialoprotein to cells occurs through a special receptor, which contains a sequence of 10 GLUs, which gives it calcium-binding properties.

About half of the CEP residues of this protein are linked to phosphate, so it can be considered a phosphoprotein. The function of the protein is not completely clear, but it is closely associated with cells and apatite. It is believed that the protein is included in the anabolic phase of bone tissue formation. Protein synthesis is inhibited by the active form of vitamin D and stimulated by a hormonal substance - dexamethasone. Bone sialoprotein has the property of selectively binding staphylococcus.

Osteopontin (molecular weight 32.6 kDa) is another anionic bone matrix protein with properties similar to bone sialoprotein, but with a lower carbohydrate content. It contains segments of negatively charged ASP, is phosphorylated at CEP, and contains the tripeptide ARG-GLI-ASP, localized in the site for specific binding to integrins. The synthesis of osteopontin is stimulated by vitamin D, which distinguishes it from bone sialoprotein. This protein is found in the light zone of osteoclasts, associated with the mineral component. These facts suggest that osteopontin is involved in attracting osteoclast precursors and binding them to the mineral matrix. This hypothesis is also supported by the fact that osteoclasts have a large number of integrin receptors that can bind to osteopontin. In addition to bone tissue, osteopontin is found in the distal tubules of the kidneys, placenta, and central nervous system.

Bone acidic glycoprotein (molecular weight 75 kDa) isolated from the mineralized matrix of bone tissue, contains a lot of sialic acids and phosphate. In bone tissue, it participates in mineralization processes along with many other acidic proteins rich in phosphate.

Osteonectin (molecular weight 43 kDa). This protein has a Ca-binding domain and several GLU-rich regions. The domain does not contain γ-carboxy-glutamic acid, although its structure resembles proteins involved in blood clotting. Osteonectin binds to collagen and apatite. This protein is widely present in tissues. It is possible that it is synthesized in any growing tissue.

Thrombospondin (molecular weight 150 kDa). The protein is widely distributed in the body, isolated from platelets and found in bones. It consists of three subunits and has the sequence ARG-GLI-ASP, which allows it to bind to cell surfaces. It also binds to other bone tissue proteins.

Bone modeling and remodeling

Bone, for all its hardness, is subject to change. Its entire dense extracellular matrix is ​​permeated with channels and cavities filled with cells, which make up about 15% of the weight of compact bone. The cells are involved in the ongoing process of bone tissue remodeling. The processes of modeling and remodeling ensure constant renewal of bones, as well as modification of their shape and structure.

Modeling is the formation of new bone that is not associated with the preliminary destruction of old bone tissue. Modeling occurs mainly in childhood and leads to changes in the architecture of the body, while in adults it leads to an adaptive modification of this architecture in response to mechanical influences. This process is also responsible for the gradual increase in vertebral size in adulthood.

Rice. 23.Bone remodeling processes (according to Bartl)

Remodeling is the dominant process in the adult skeleton and is not accompanied by a change in the structure of the skeleton, since in this case only a separate section of the old bone is replaced with a new one ( rice. 23). This bone renewal helps maintain its mechanical properties. From 2 to 10% of the skeleton per year undergoes remodeling. Parathyroid hormone, thyroxine, growth hormone and calcitriol increase the rate of remodeling, while calcitonin, estrogens and glucocorticoids reduce it. Stimulating factors include the occurrence of microcracks and, to a certain extent, mechanical influences.

Mechanisms of bone tissue formation

The bone matrix is ​​regularly renewed ( rice. 23). Bone formation is a complex process involving many components. Cells of mesenchymal origin - fibroblasts and osteoblasts - synthesize and release collagen fibrils into the environment, which penetrate into a matrix consisting of glycosaminoglycans and proteoglycans.

Mineral components come from the surrounding liquid, which is “supersaturated” with these salts. First, nucleation occurs, i.e. the formation of a surface with crystallization nuclei, on which the formation of a crystal lattice can easily occur. The formation of bone mineral crystals triggers collagen. Electron microscopy studies have shown that the formation of a crystal lattice of minerals begins in zones located in regular spaces that appear between the fibers of collagen fibrils when they are shifted by ¼ of their length. The first crystals then become nucleation centers for the total deposition of hydroxyapatite between the collagen fibers.

Active osteoblasts produce osteocalcin, which is a specific marker of bone remodeling. Having γ-carboxyglutamic acid, osteocalcin is combined with hydroxyapatite and binds Ca 2+ in bones and teeth. Once in the blood, it undergoes rapid splitting into fragments of different lengths ( rice. 25), which are detected by enzyme immunoassay methods. In this case, specific regions of the N-MID and N-terminal fragments of osteocalcin are recognized, therefore the C-terminal region is detected regardless of the degree of cleavage of the polypeptide molecule.

Bone formation occurs only in the immediate vicinity of osteoblasts, with mineralization beginning in cartilage, which consists of collagen embedded in a proteoglycan matrix. Proteoglycans increase the elasticity of the collagen network and increase the degree of its swelling. As the crystals grow, they displace proteoglycans, which are degraded by lysosomal hydrolases. Water is also displaced. Dense, fully mineralized bone is virtually dehydrated. Collagen makes up 20% by weight.

Rice. 25.Circulating fragments of osteocalcin (numbers are the serial number of amino acids in the peptide chain)

Bone mineralization is characterized by the interaction of 3 factors.

1). Local increase in phosphate ion concentration. Alkaline phosphatase, which is found in both osteoblasts and osteoclasts, plays an important role in the ossification process. Alkaline phosphatase is involved in the formation of basic organic matter of bone and mineralization. One of the mechanisms of its action is a local increase in the concentration of phosphorus ions to the saturation point, followed by the processes of fixation of calcium-phosphorus salts on the organic matrix of the bone. When bone tissue is restored after fractures, the content of alkaline phosphatase in callus increases sharply. When bone formation is impaired, the content and activity of alkaline phosphatase in bones, blood plasma and other tissues decreases. With rickets, which is characterized by an increase in the number of osteoblasts and insufficient calcification of the main substance, the content and activity of alkaline phosphatase in the blood plasma increases.

2). Adsorption of Ca 2+ ions. It has been established that the incorporation of Ca 2+ into bones is an active process. This is clearly proven by the fact that living bones perceive Ca 2+ more intensely than strontium. After death, such selectivity is no longer observed. The selective ability of bone in relation to calcium depends on temperature and appears only at 37 o C.

3). pH shift. During the mineralization process, pH matters. When the pH of bone tissue increases, calcium phosphate is deposited into the bone more quickly. Bone contains a relatively large amount of citrate (about 1%), which helps maintain pH.

Bone decay processes

During the destruction of the bone matrix, type I collagen is broken down and small fragments enter the bloodstream. Pyridinoline cross-links, cross-linked C- and N-telopeptides, and specific amino acids are excreted in the urine. Quantitative analysis of type I collagen degradation products allows us to estimate the rate of bone resorption. The most highly specific markers of bone resorption are peptide fragments of collagen-I.

C-telopeptide cleavage occurs at the very initial stage of collagen degradation. As a result, other collagen metabolites have virtually no effect on its concentration in the blood serum. The C-telopeptide cleavage products of type I collagen consist of two octapeptides present in the β-form and linked by cross-linking (these structures are called β-Crosslaps). They enter the blood, where their quantity is determined by enzyme immunoassay. In newly formed bone, the terminal linear octapeptide sequences contain α-aspartic acid, but as bone ages, α-aspartic acid isomerizes to the β form. The monoclonal antibodies used in the analysis specifically recognize octapeptides containing β-aspartic acid ( rice. 26).

Rice. 26.Specific β-octapeptides in the composition of collagen C-telopeptide

There are markers of bone formation and resorption that characterize the functions of osteoblasts and osteoclasts ( table).

Table.Biochemical markers of bone metabolism

Bone formation markers	Markers bone resorption
plasma: osteocalcin, total and specific bone alkaline phosphatase, procollagen C- and N-peptides	plasma: tartrate-resistant acid phosphatase, pyri dinoline and deoxypyridinoline, degradation products of type I collagen (N - and C-telopeptides); urine: pyridinoline and deoxypyridinoline, collagen degradation products Type I – N - and C-telopeptides, calcium andFasting hydroxyproline and hydroxylysine glycosides

Biochemical markers provide information about the pathogenesis of skeletal diseases and the rate of remodeling. They can be used to monitor the effectiveness of treatment in the short term and identify patients with rapid bone loss. Biochemical markers measure the average rate of remodeling of the entire skeleton, rather than individual regions.

Aging of bones.During adolescence and young adulthood, bone massis constantly increasing and reaching maximum by the age of 30-40. Typically, total bone mass in womenless than in men, as a result of smaller bone volume; ButBone density is the same in both sexes.As both men and women age, they begin to losebone mass, but the dynamics of this process varydepending on gender. From about 50 years of age in individualsIn both sexes, bone mass decreases linearly by 0.5-1.0% per year. From a biochemical point of view, the composition and balance of the organic and mineral components of bone tissue do not change, but its quantity gradually decreases.

Pathology of bone tissue.Normal amount of newly formed bone tissueequivalent to the amount destroyed. Due to disturbances in the processes of bone mineralization, excessive accumulation of organic matrix can occur - osteomalacia. Due to improper formation of the organic matrix and a decrease in its calcification, another type of dysosteogenesis can form - osteoporosis. In both the first and second cases, disturbances in bone tissue metabolism affect the condition of the tooth tissues and the alveolar process of the jaw bone.

Osteomalacia – softening of bones due to disruption of the formation of the organic matrix and partial resorption of bone tissue minerals. The pathology is based on: 1) synthesis of excess amounts of osteoid during bone remodeling, 2) decreased mineralization (leaching of the mineral phase from the bone). The disease is affected by prolonged immobility, poor nutrition, especially deficiency of ascorbate and vitamin D, as well as impaired metabolism of vitamin D and a defect in intestinal or other receptors for calcitriol and calcitonin.

Osteoporosis - This is a general degeneration of bone tissue, based on the loss of part of both organic and inorganic components. P In osteoporosis, bone destruction is not compensated forformation, the balance of these processes becomes negative. Osteoporosis often occurs due to a lack of vitamin C, poor nutrition, and prolonged immobility.

Osteoporosis is a systemic bone disease and involves not only loss of bone mass, but also disruption of bone microarchitecture, leading to increased bone fragility and an increased risk of fractures. Osteoporosis is characterized by a decrease in bone crossbars per unit volume of bone, thinning and complete resorption of some of these elements without reducing the size of the bone:

Rice. 27. Changes in bone structure in osteoporosis (according to N. Fleish)

Regulation of osteogenesis of bone and dense dental tissues by proteins

Bone tissue, a type of which is dentin and dental cement, contains up to 1% of proteins that regulate osteogenesis. These include morphogens, mitogens, chemotaxis and chemoattraction factors. These are mainly bone proteins, but some of them are important in the construction of dental tissue.

Morphogens - these are glycoproteins released from decaying bone tissue and acting on pluripotent cells, causing their differentiation in the desired direction.

The most important of them is bone morphogenetic protein, consisting of four subunits with a total molecular weight of 75.5 kDa. Osteogenesis under the influence of this protein proceeds according to the enchondral type, i.e. First, cartilage is formed, and then bone is formed from it. This protein is obtained in its pure form and is used for poor bone regeneration.

Highlighted but little studied Thielmann factor with a molecular weight of 500-1000 kDa, which quickly causes intramembranous osteogenesis (without cartilage formation), but in a small volume. This is how the lower jaw bone develops.

A morphogenetic factor is also obtained from dentin - protein that stimulates dentin growth. No morphogens were found in the enamel.

Mitogens (most often glycophosphoproteins) act on predifferentiated cells that have retained the ability to divide and increase their mitotic activity. The biochemical mechanism of action is based on the initiation of DNA replication. Several factors have been isolated from bone: bone-extractable growth factor, skeletal growth factor. No mitogens have yet been detected in dentin and enamel.

Factors of chemotaxis and chemoattraction are glycoproteins that determine the movement and attachment of newly formed structures under the influence of morpho- and mitogens. The most famous of them are: fibronectin, osteonectin and osteocalcin. Due to fibronectin and interaction between cells and substrates occurs, this protein promotes the attachment of gum tissue to the jaw. Osteonectin, being a product of osteoblasts, determines the migration of preosteoblasts and the fixation of apatites on collagen, that is, with its help, the mineral component binds to collagen. Osteocalcin– a protein that marks areas of bone that should undergo decay (resorption). Its presence at an old site of bone (to which an osteoclast must attach to destroy the site) promotes chemotaxis of osteoclasts to that site. This protein contains γ-carboxyglutamic acid and is vitamin K dependent. Consequently, osteocalcin belongs to the group of so-called gla proteins, which are the initiators of mineralization and create crystallization nuclei. In enamel, similar functions are performed by amelogenins.

Morphogens, mitogens, chemotaxis and chemoattraction factors perform an important biological function, combining the process of tissue destruction and new formation. As cells break down, they release them into the environment, where these factors cause the formation of new tissue areas, affecting different stages of differentiation of precursor cells.

Compounds called Keylons , the effect of which is opposite to the influence of morpho- and mitogens. They bind strongly to morphogens and mitogens and prevent bone regeneration. In this regard, an important problem arises in developing methods for regulating the synthesis of morpho-, mitogens, and chemotaxis factors.

It is known that the synthesis of bone morphogens is stimulated by active forms of vitamin D (calcitriols) and thyrocalcitonin, and suppressed by glucocorticosteroids and sex hormones. Consequently, a decrease in the production of sex hormones during menopause, as well as the use of glucocorticosteroids, reduce the regenerative capabilities of bone and contribute to the development of osteoporosis. Complications in the process of healing (consolidation) of fractures are possible in cases where the patient has already been treated with glucocorticosteroids or anabolic steroids. In addition, long-term use of anabolic steroids can provoke a fracture, since active growth of muscle mass will be accompanied by a decrease in skeletal strength. It should also be noted that the speed and completeness of bone defect replacement during bone grafting is determined by the amount of morphogens in the grafted tissue. Therefore, the older the donor is, the less likely it is to successfully replace the defect. Bone taken from young donors will not be replaced well if they have a immediate history of treatment with glucocorticosteroids or anabolic hormones. These aspects of the biochemical regulation of osteogenesis must be taken into account in the practice of dental implantology.

Effect of pyrophosphate and bisphosphonates on bone resorption

Pyrophosphate (pyrophosphoric acid) is a metabolite formed during enzymatic reactions by splitting off from ATP. It is then hydrolyzed by pyrophosphatase, so there is very little pyrophosphate in the blood and urine. However, in bones, pyrophosphate (as a representative of polyphosphates) binds to hydroxyapatite crystals, limiting their overly active growth like ectopic calcification.

The structure of pyrophosphate( A) and bisphosphonates( B), used in the treatment of osteoporosis

Bisphosphonates have a high structural similarity to pyrophosphate, but theyThe P-C-P bond is very stable and resistant to cleavage, unlike the P-O-P bond inpyrophosphate. Like pyrophosphate, bisphosphonates have negative charges (OH → O – transition) and easily bind to Ca 2+ ions on the crystal surface hydroxyapatite.

Affinity for calcium increasespresence of -OH groups on site - R 1 . As a result, not only the growth of crystals stops, but also their dissolution, so bone resorption stops. Antiresorptive propertiesbisphosphonates intensified due to the effect on osteoclasts, especially if in place - R 2 there is an aromatic heterocycle containing 1-2 nitrogen atoms. Accumulating in the acidic environment of the bone resorption zone,bisphosphonates penetrate into the osteoclast (the main mechanism is endocytosis), are incorporated, like pyrophosphate, into enzymes, ATP and interfere with their normal functioning, which leads to disruption of metabolism, energy metabolism of the cell, and then to its death. A decrease in the number of osteoclasts helps to reduce their resorptive effect on bone tissue. Various substituents R 1 and R 2 initiate the appearance of a number of additional side effects of bisphosphonates.

Calcium phosphates are the basis of the mineral component of the intercellular matrix

Calcium orthophosphates are salts of tribasic phosphoric acid. Phosphate ions (PO 4 3 – ) and their mono- and disubstituted forms (H 2 PO 4 – and HPO 4 2 – ). All calcium phosphate salts are white powders that are slightly soluble or insoluble in water, but soluble in dilute acids. The composition of the tissues of teeth, bones and dentin includes HPO 4 2 salts – or PO 4 3– . Pyrophosphates are found in dental calculus. In solutions, the pyrophosphate ion has a significant effect on the crystallization of some calcium orthophosphates. This effect is believed to be important for controlling the size of crystals in bones containing small amounts of pyrophosphate.

Natural forms of calcium phosphates

Whitlockit – one of the forms of anhydrous tricalcium phosphate – βСа 3 (PO 4) 2. Whitlockite contains divalent ions (Mg 2 + Mn 2+ or Fe 2+), which are part of the crystal lattice, for example, (CaMg) 3 (PO 4) 2. About 10% of the phosphate in it is in the form of HPO 4 2 – . The mineral is rarely found in the body. It forms rhombic crystals, which are found in the composition of dental calculus and in areas of carious enamel damage.

Monetit (CaHPO 4) and brushes (CaHPO 4 ·2H 2 O) – secondary salts of phosphoric acid. Also rarely found in the body. Brushite is found in dentin and dental calculus. Monetite crystallizes in the form of triangular plates, but sometimes there are rods and prisms. Brushite crystals are wedge-shaped. The solubility of monetite crystals is pH dependent and increases rapidly below pH 6.0. The solubility of brushite under these conditions also increases, but to an even greater extent. When heated, brushite turns into monetite. During long-term storage, both minerals are hydrolyzed into hydroxyapatite Ca 10 (PO 4) 6 (OH) 2.

Accordingly, along with monocalcium phosphate in the composition of amorphous salts bone, tooth, tartar there are intermediate hydrated di-, tri-, tetracalcium phosphates . In addition, there is calcium pyrophosphate dihydrate . The amorphous phase of bone is a mobile depot of minerals in the body.

Octacalcium phosphate Ca 8 (HPO 4) 2 (PO 4) 4 5H 2 O, its formula is also represented as Ca 8 H 2 (PO 4) 6 5H 2 O. It is the main and last intermediate link between acid phosphates - monetite and brushite, and the main salt - hydroxyapatite. Like brushite and apatite it part of bone, tooth, tartar. As can be seen from the formula, octacalcium phosphate contains an acidic phosphate ion, but does not have hydroxyl ions. The water content in it varies widely, but more often 5H 2 O. In its structure, it resembles apatite crystals; it has a layered structure with alternating layers of salt 1.1 nm thick and layers of water 0.8 nm thick. Given its close relationship with apatites, it plays an important role in the nucleation of apatite salts. Crystals of octacalcium phosphate grow in the form of thin plates up to 250 microns in length. Like monetite and brushite, octacalcium phosphate is unstable in water, but it is the one that hydrolyzes most easily into apatite, especially in a warm alkaline solution. Low concentrations of fluorine (20-100 µg/l) sharply accelerate the rate of hydrolysis, therefore F - ions are necessary for the deposition of apatite in dense tissues.

Apatity . Apatites have the general formula Ca 10 (PO 4) 6 X 2, where X is most often OH – or F – . Fluorapatites Ca 10 (PO 4) 6 F 2 are widespread in nature, primarily as soil minerals. They are used to produce phosphorus in industry. Hydroxyapatites Ca 10 (PO 4) 6 (OH) 2 predominate in the animal world. They are the main form in which calcium phosphates are present in bones and teeth. Hydroxyapatites form a very stable ionic lattice (melting point more than 1600º C), the ions in it are retained due to electrostatic forces and are in close contact with each other. Phosphate ions PO 4 3 – They are the largest in size and therefore occupy a dominant position in the ionic lattice. Each phosphate ion is surrounded by 12 neighboring Ca 2+ and OH ions – , of which 6 ions are located in the same layer of the ionic lattice where the PO 4 3 ion is located – , and in the above and below layers of the ionic lattice there are 3 more ions. Ideal hydroxyapatite forms crystals that have a hexagonal shape when cut ( rice. 31). Each crystal is covered with a hydration shell, and there are spaces between the crystals. The sizes of hydroxyapatite crystals in dentin are smaller than in enamel.

Rice. 31. Hexagonal model of hydroxyapatite crystals

Apatites are fairly stable compounds, but are able to exchange with the environment. As a result, other ions appear in the lattice of hydroxyapatite crystals. However, only some ions can be included in the structure of hydroxyapatites. The predominant factor determining the possibility of replacement is the size of the atom. Similarity in charges is of secondary importance. This replacement principle is called isomorphic substitution, during which the general distribution of charges is maintained according to the principle: Ca 10-x (HPO 4) x (PO 4) 6-x (OH) 2-x, where 0<х<1. Потеря ионов Ca 2+ частично компенсируется потерей ионов OH – и присоединением ионов H + к фосфату.

This leads to a change in the shape and size of the crystals, which affects the properties of hydroxyapatites. Reactions of isomorphic substitution of ions significantly affect the strength and growth of hydroxyapatite crystals and determine the intensity of mineralization processes of hard dental tissues.

Table 9. Replaceable ions and substituents in the composition of hydroxyapatites

Replaceable ions	Deputies
Ca2+	Mg 2+ , Sr 2+ , Na + , less common: Ba 2+, Pb 2+, M o 2+, Cr 2+, K +, H 3 O +, 2H +
PO 4 3–	HPO 4 2–, CO 3 2–, C 6 H 3 O 6 3– (citrate), H 2 PO 4 –, AsO 3 3–
OH –	F – , Cl – , Br – , J – , less often: H 2 O, CO 3 2–, O 2

1. Replacement of calcium ions (Ca 2+) with protons (H +), hydronium ions (H 3O+), strontium (Sr 2+), magnesium (Mg 2+) and other cations.

In an acidic environment, calcium ions are replaced by protons according to the following scheme:

Ca 10 (PO 4) 6 (OH) 2 + 2H + → Ca 9 H 2 (PO 4) 6 (OH) 2 + C a 2+.

Ultimately, the acid load leads to the destruction of the crystals.

Magnesium ions can displace calcium or occupy vacant positions in hydroxyapatite crystals with the formation magnesium apatite :

Ca 10 (PO 4) 6 (OH) 2 + Mg 2+ → Ca 9 Mg (PO 4) 6 (OH) 2 + C a 2+

This substitution is characterized by a decrease in the molar Ca/P coefficient and leads to a disruption of the structure and a decrease in the resistance of hydroxyapatite crystals to adverse effects of a physical and chemical nature.

In addition to magnesium apatite, less mature forms of magnesium minerals are found in the oral cavity: neuberite – Mg HPO 4 3H 2 O and struvite – Mg HPO 4 6H 2 O. Due to the presence of magnesium ions in saliva, these minerals are formed in small quantities as part of dental plaque and further as it mineralizes to the state stone can mature to apatite forms.

Strontium ions, similar to magnesium ions, can displace calcium or replace vacant places in the crystal lattice of hydroxyapatites, forming strontium apatite :

Ca 10 (PO 4) 6 (OH) 2 + Sr 2+ → Ca 9 Sr (PO 4) 6 (OH) 2 + C a 2+.

When supplied in excess, strontium, although it displaces calcium from the crystal lattice, is not retained in it, which leads to bone porosity. This effect is exacerbated by calcium deficiency. Such changes are characteristic of Kashin-Beck disease (“Urov disease”), which affects people, mainly in early childhood, living in the valley of the Urov River in the Trans-Baikal Territory, the Amur Region and adjacent provinces of China. Suffering begins with pain in the joints, then damage to bone tissue occurs with softening of the epiphyses, and ossification processes are disrupted. The disease is accompanied by short-fingered feet. In endemic areas, soil and water contain 2.0 times less calcium and 1.5-2.0 times more strontium than normal. There is another theory of the pathogenesis of “level disease”, according to which the pathology develops as a result of an imbalance of phosphates and manganese in the environment, which is also typical for these areas. It is likely that both of these theories complement each other.

In areas contaminated with radionuclides, the adverse effect of strontium apatite on the human body is aggravated by the possibility of deposition of radioactive strontium.

2. Replacement of phosphate ions (PO 4 3–) with hydrophosphate ions (HPO 4 2–) or with carbonate and hydrocarbonate ions (CO 3 2– and HCO 3–).

Ca 10 (PO 4) 6 (OH) 2 + HPO 4 2– → Ca 10 (HPO 4)(PO 4) 5 (OH) 2 + PO 4 3–

In this case, the charge of calcium cations is not completely compensated by anions (the ionic radius is more important, not the charge of the substituent). Double replacement leads to instability of the Ca 2+ ion; it can leave the crystal:

Ca 10 (PO 4) 6 (OH) 2 + 2HPO 4 2– → Ca 9 (HPO 4) 2 (PO 4) 4 (OH) 2 + Ca 2+ + 2PO 4 3–

Substitution with carbonate ion leads to the formation carbonate apatites and increases the Ca/P ratio, but the crystals become looser and more fragile.

Ca 10 (PO 4) 6 (OH) 2 + CO 3 2– → Ca 10 (PO 4) 5 (CO 3)(OH) 2 + PO 4 3–

The intensity of the formation of carbonate-apatites depends on the total amount of bicarbonates in the body, diet and stress loads.

Ca 10 (PO 4) 6 (OH) 2 + 3 HCO 3 – +3H + → Ca 10 (PO 4) 4 (CO 3) 3 (OH) 2 + 2H 3 PO 4

Ca 10 (PO 4) 6 (OH) 2 + 3CO 3 2– → Ca 10 (PO 4) 4 (CO 3) 3 (OH) 2 + 2PO 4 3–

In general, if a basic calcium phosphate salt is precipitated at room or body temperature in the presence of a carbonate or bicarbonate ion, the resulting apatite will contain several percent carbonate or bicarbonate. Carbonate reduces the crystallinity of apatite and makes it more amorphous. This structure resembles the structure of apatite bones or enamel. With age, the amount of carbonate apatites increases.

Of the carbon-containing minerals, in addition to carbonate apatite, there are calcium bicarbonate Ca(HCO 3) 2 and leads CaC 2 O 4 H 2 O as a minor component tartar.

3. Replacement of hydroxyl (OH –) with fluorides (F –), chlorides (Cl –) and other ions:

In an aqueous environment, the interaction of F ions – with hydroxyapatite depends on the fluoride concentration. If the fluorine content is relatively low (up to 500 mg/l), then replacements occur and crystals of hydroxyfluorine or fluorapatite:

Ca 10 (PO 4) 6 (OH) 2 + F – → Ca 10 (PO 4) 6 ONF + OH –

Ca 10 (PO 4) 6 (OH) 2 + 2F – → Ca 10 (PO 4) 6 F 2 + 2OH –

Hydroxyfluorapatite – Ca 10 (PO 4) 6 (OH ) F is an intermediate option between hydroxyapatite and fluorapatite. Fluorapatite – Ca 10 (PO 4) 6 F 2 – the most stable of all apatites, melting point 1680º C. Fluorapatite crystals have a hexagonal shape: a axis = 0.937 nm, c axis = 0.688 nm. The crystal density is 3.2 g/cm 3 .

Both reactions of substitution of OH ions in the crystal lattice - by F ions - sharply increase the resistance of hydroxyapatites to dissolution in an acidic environment. This property of hydroxyfluoro- and fluorapatites is considered as a leading factor in the preventive effect of fluorides against caries. Zinc and tin ions have the same, but much lesser effect. On the contrary, in the presence of carbonate and citrate ions, the solubility of apatite crystals increases:

Ca 10 (PO 4) 6 (OH) 2 + CO 3 2– + 2H + → Ca 10 (PO 4) 6 CO 3 + 2H 2 O

At the same time, high concentrations of F – ions (more than 2 g/l) destroy apatite crystals:

Ca 10 (PO 4 ) 6 (OH ) 2 + 20 F – → 10 CaF 2 +6 PO 4 3– + 2 OH – .

Emerging calcium fluoride – CaF 2 – insoluble compound, can be included in the composition of dental plaque and tartar. In addition, under these conditions, fluoride ions will bind calcium ions on the surface of the tooth, preventing them from penetrating into the enamel.

The composition of dental calculus is also found octalcium fluorapatite Ca 8 (PO 4) 6 F 2, this type of mineral is formed gradually as the stone ages.

Stages of exchange of elements of the apatite crystal lattice

When formed in solutions, apatite crystals can change due to exchange with ions present in the same solution. In living systems, this property of apatites makes them highly sensitive to the ionic composition of the blood and intercellular fluid, and this, in turn, depends on the nature of the food and the composition of the water consumed. The process of exchange of crystal lattice elements itself occurs in several stages, each of which has its own speed.

First stage proceeds quite quickly - within a few minutes. This is an exchange through diffusion between the hydration shell of the crystal and the mobile liquid in which the crystal is immersed. The exchange leads to an increase in the concentration of individual ions in the immediate vicinity of the crystal. This stage involves many ions, different in size and properties.

At the second stage there is an exchange between the ions of the hydration shell and the surface of the crystals. Here, elements are separated from the surface of the crystal and replaced with ions coming from the hydration shell. The process includes mainly ions of calcium, magnesium, strontium, sodium, phosphoric and carbonic acids, fluorine, chlorine, and sometimes other ions approximately equal in size. Many ions cannot cope with this stage. The duration of the stage is several hours.

At the third stage ions penetrate deep into the crystal lattice. This is the slowest process, lasting weeks, months, sometimes more than a year. The stage takes place in the form of isomorphic replacement or filling of vacant positions. The main ions here are calcium, magnesium, phosphate, strontium, and fluorine.

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 is 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.

The skeleton of any adult human includes 206 different bones, all of them different in structure and role. At first glance, they appear hard, inflexible and lifeless. But this is a mistaken impression; various metabolic processes, destruction and regeneration continuously occur in them. They, together with muscles and ligaments, form a special system called “musculoskeletal tissue,” the main function of which is musculoskeletal. It is formed from several types of special cells that differ in structure, functional features and significance. Bone cells, their structure and functions will be discussed further.

The structure of bone tissue

Features of lamellar bone tissue

It is formed by bone plates having a thickness of 4-15 microns. They, in turn, consist of three components: osteocytes, ground substance and collagen thin fibers. All bones of an adult are formed from this tissue. The collagen fibers of the first type lie parallel to each other and are oriented in a certain direction, while in neighboring bone plates they are directed in the opposite direction and intersect almost at a right angle. Between them are the bodies of osteocytes in the lacunae. This structure of bone tissue provides it with the greatest strength.

Cancellous bone

The name "trabecular substance" is also found. If we draw an analogy, the structure is comparable to an ordinary sponge, built from bone plates with cells between them. They are arranged in an orderly manner, in accordance with the distributed functional load. The epiphyses of long bones are mainly built from spongy substance, some are mixed and flat, and all are short. It can be seen that these are mainly light and at the same time strong parts of the human skeleton, which experience loads in different directions. The functions of bone tissue are in direct relationship with its structure, which in this case provides a large area for the metabolic processes carried out on it, gives high strength combined with low mass.

Dense (compact) bone substance: what is it?

The diaphyses of the tubular bones consist of a compact substance; in addition, it covers their epiphyses from the outside with a thin plate. It is pierced by narrow channels, through which nerve fibers and blood vessels pass. Some of them are located parallel to the bone surface (central or Haversian). Others emerge on the surface of the bone (nutrient openings), through which arteries and nerves penetrate inward, and veins penetrate outward. The central canal, together with the bone plates surrounding it, forms the so-called Haversian system (osteon). This is the main content of the compact substance and they are considered as its morphofunctional unit.

Osteon is a structural unit of bone tissue

Its second name is the Haversian system. This is a collection of bone plates that look like cylinders inserted into each other, the space between them is filled by osteocytes. In the center is the Haversian canal, through which the blood vessels that ensure metabolism in bone cells pass. Between adjacent structural units there are intercalary (interstitial) plates. In fact, they are the remnants of osteons that existed previously and were destroyed at the moment when the bone tissue underwent restructuring. There are also general and surrounding plates; they form the innermost and outer layers of the compact bone substance, respectively.

Periosteum: structure and significance

Based on the name, we can determine that it covers the outside of the bones. It is attached to them with the help of collagen fibers, collected in thick bundles, which penetrate and intertwine with the outer layer of bone plates. It has two distinct layers:

• external (it is formed by dense fibrous, unformed connective tissue, it is dominated by fibers located parallel to the surface of the bone);
• the inner layer is well defined in children and less noticeable in adults (formed by loose fibrous connective tissue, which contains spindle-shaped flat cells - inactive osteoblasts and their precursors).

The periosteum performs several important functions. Firstly, trophic, that is, it provides the bone with nutrition, since it contains vessels on the surface that penetrate inside along with the nerves through special nutrient openings. These channels feed the bone marrow. Secondly, regenerative. It is explained by the presence of osteogenic cells, which, when stimulated, transform into active osteoblasts that produce matrix and cause the growth of bone tissue, ensuring its regeneration. Thirdly, the mechanical or support function. That is, ensuring the mechanical connection of the bone with other structures attached to it (tendons, muscles and ligaments).

Functions of bone tissue

Among the main functions are the following:

1. Motor, support (biomechanical).
2. Protective. Bones protect the brain, blood vessels and nerves, internal organs, etc. from damage.
3. Hematopoietic: hemo- and lymphopoiesis occurs in the bone marrow.
4. Metabolic function (participation in metabolism).
5. Reparative and regenerative, consisting in the restoration and regeneration of bone tissue.
6. Morph-forming role.
7. Bone tissue is a kind of depot of minerals and growth factors.