The bone tissue is a particular type of support connective tissue that derives from hyaline cartilage, whose extracellular matrix rich in calcium imprisons the cells that produced it. Calcium is found in the form of tricalcium phosphate, a salt that is deposited in the form of hydroxyapatite crystals. Then there are other salts such as calcium carbonate and calcium fluoride. The TO is then mineralized and this gives it special characteristics: it is a resistant tissue, but has a certain degree of flexibility and lightness. The bone tissue form the bones that make up the skeleton of vertebrates.
The bone consists of a central part named diaphysis and two rounded ends named epiphysis. During the development of skeleton, between diaphysis and epiphysis is present a layer of cartilage, called conjugation cartilage or growth plate. As long as this cartilage is not mineralized and ossified, bone lengthening is possible.
The bone is also almost totally coated on the outer surface of a membrane of dense and elastic connective named periosteum, consisting of collagen fibers and fibroblasts, and osteogenic cells in contact with the bone which differentiate into osteoblasts; with the the exception of epiphyseal articular surfaces that are coated with an encrustation of hyaline cartilage.
The cavities that are located within the bones are instead covered with a layer of reticular connective with osteoprogenitor cells called endosteum, thinner than the periosteum which has the function of providing nourishment and new bone cells.
Even the Bone Tissue, such as all kinds of connective tissue, is made of cells and an abundant proteic matrix produced by cells of the tissue in which the cells themselves are immersed. This matrix is constituted by an organic portion, and an inorganic or mineral component.
It consists of bundles of collagen fibers (Type I) and an amorphous substance of proteoglycanic nature which however, in the bone is very low (1-2% of the dry weight of the bone). There are also different glycoproteins, with the role of adhesion proteins and a function to anchor the cells to the matrix (osteonectin and osteopontin) and sialoprotein.
It consists mainly of Ca combined with oxygen, phosphorus and hydrogen to form a crystalline molecule defined hydroxyapatite (Ca10(PO4)6(OH)2) which forms thin needle-like crystals. These crystals are placed in relationship with the collagen fibers and it is believed that the typical striation of collagen serves as a template for the deposition of hydroxyapatite crystals.
The different components of the matrix give different and interdependent properties to the tissue: the calcified fraction is responsible for the hardness of the bone, while the fibrillar is responsible for the flexibility, strength and the tensile strength of the tissue.
The Bone tissue may assume a non-lamellar organization which is found in the early stages of bone formation, in the early stages of bone repair, eg. as a result of fracture and on the insertion points of tendons. In this type of organization the collagen fibers are not organized in stratified lamellas but shall run in thick bundles intertwined with gaps irregularly dispersed in the matrix.
The lamellar organization instead is the result of the non-lamellar bone remodeling, that is found in the adult. It consists of layers of parallel lamellae overlapped each other, and the collagen fibers are oriented in the same direction in the same layer and in different directions with respect to the near lamellae. In this type of organization can be distinguished thus:
According to their shape the bones can be classified as follows into:
The bone lamellae can be arranged in various ways; for example in the long bones some lamellae forming the outer circumferential system that encloses the bone below the periosteum. Behind the medullary cavity there are other 2-3 lamellae that form the inner circumferential system; between these two systems there are osteons, also called Haversian systems, which look like solid cylinders that have, in longitudinal direction, a cavity that contains blood vessels. The lamellae of osteons are arranged concentrically around the central channel called Haversian channel. The Volkman channels are other vascular channels which run perpendicularly to the major axis of the osteons. Finally other lamellae form a system called interstitial system of bone which is located between the osteons; They are osteons in resorption which thus take a polyhedral shape to adapt to the surfaces of the surrounding osteons.
The formation of bone tissue or Ossification is the process of creating bone through the deposition of extracellular material and its calcification and it can occur in two ways:
The bone that is formed by the two processes have the same histological structure. Initially it will be the primary bone, which is the immature form present during embryonic development and during the reparative processes (eg. fractures). It has many osteocytes and interwoven collagen fibers, with a lower mineral content than mature bone. Following the primary bone is replaced by secondary or mature bone constituted by parallel or concentric lamellae (osteon).
The direct ossification is the type of ossification easier because there are no significant changes in tissue, rather typical of indirect ossification. It takes place in a few bones (eg, flat bones of the skull) and is carried out in the primitive connective tissue of mesenchymal derivation. The mesenchyme condenses and vascularzes while its cells actively proliferate and differentiate into pre-osteoblasts. Subsequently these elements changes and becomes osteoprogenitor cells and osteoblasts. Osteoblasts begin to secrete a primitive bony matrix and a fundamental substance denser than the surrounding mesenchyme and are arranged in single or double row. Then the first trabeculae are formed in which a part of the connective tissue, derived from the mesenchyme, remains locked and differs in Marrow. These trabeculae are surrounded by one or two layers of osteoblasts aligned with epithelioid appearance. The matrix or intercellular fundamental substance is, at the beginning, devoid of minerals for which it is called osteoid tissue; it quickly undergoes the mineralization through the deposition of calcium salts, and gives rise to the Primary Centers of Ossification. The first trabecula then grows by apposition of osteoblasts arranged around it which produce a new layer of osteoid tissue. Some osteoblasts are enclosed in the calcified osteoid tissue and emit extensions thus transforming into osteocytes; meanwhile the osteoid tissue calcifies and mineralizes, the bodies and extensions of osteocytes remain imprisoned within lacunae and canaliculi. At the same time around the growing trabeculae form new layers of osteoblasts. So spicules and trabeculae are formed and the latter converge and merge.
The indirect ossification provides for the complete or partial replacement of a previous cartilage tissue by newly formed bone tissue through a process consisting of several stages. The cartilage tissue is in fact the precursor of the whole adult bone system and, not being able to guarantee resistance to flexural or high compressions, needs to be replaced by more solid bone. It occurs for example in the limbs where however the chondral mechanism also cooperates with the membranous mechanism to form the various parts of long bones (diaphysis, epiphysis, metaphysis).
In the indirect ossification are distinguished:
During the indirect ossification some osteoprogenitor cells in the diaphysis begin to differentiate into osteoblasts forming the perichondrium from which, during a subsequent modification, the periosteum is formed. The perichondrium/periosteum is the most external part of the bone and differs form endochondrium/endosteum which is the innermost part, close to the medullary canal.
In the endosteum there are some blood vessels that carry fibroblasts, which differentiate into osteoblasts. These begin to lay matrix to form a kind of spongy bone tissue, which subsequently forms the medullary canal. In a long bone the endochondral ossification is observed in the center of the diaphysis. The cartilage cells proliferate and became hyper trophic and gaps that contain them get bigger at the expense of the matrix which is calcified by deposition of calcium salts. As a result the hypertrophic cells degenerate and die. The partitions of matrix between the gaps became thinner and the gaps merge to form large cavities. Around the middle portion of the diaphysis, some cells of the deep layer of the perichondrium, differentiate in osteoprogenitor cells and then into osteoblasts that produce the thin layer of perforated bone tissue called sleeve or periosteal collar. From the periosteum that envelops this collar through the openings of the latter are observed cords of vascularized connective tissue that penetrate in the diaphysis and invade the cavities that are formed in the calcified cartilage. These cavities become primitive marrow spaces and the connective cords that fill them contain both blood vessels and cells with hematopoietic potential and osteoprogenitor cells. The latter differentiate into osteoblasts and deposited on the trabecular calcified cartilage, osteoid tissue that quickly calcify.
During the growth of the bone, trabeculae of calcified cartilage and their bony coating are reabsorbed thanks to osteoclast activity so that the first sketch of the medullary cavity of the diaphysis constitutes.
So in the long bones the first ossification occurs in the diaphysis. After a period of proliferation, chondrocytes resorb the matrix and increase in volume. Then in the matrix diffuse salts of calcium, collagen, growth factors and osteoclasts that degrade the cartilage invaded by vessels and osteoblasts of the periosteum. The spongy tissue is not reabsorbed but form the marrow. The bony sleeve form the compact lamellar bone tissue that produce more matrix, which extends at the expense of the cartilage. While the cartilage retreats and the compact bone tissue increases, the intermediate zone is called metaphysis or growth plate or conjugation cartilage. The latter for the entire period of the body development extends for interstitial growth on the side facing the epiphysis, while it is simultaneously replaced by bone on the side facing the center of diaphysis.
In conjugation cartilage distinguish different zones which, going from epiphysis to the diaphysis, are:
Subsequently, the process of ossification extends at both ends of the diaphysis, toward the epiphysis. The final balance occurs when the cartilage remains in a constant quantity. After the age of development the cartilage disappears completely. In short bones you have the same process but the cartilage radiates in all directions, not only toward the epiphysis.
After birth in both epiphyses appear the Epiphyseal or Secondary Ossification Centers, in which will be the endochondral ossification. In the epiphysis, when the cartilage cells proliferate give rise to cells that are arranged to form groups or nests, so that an epiphyseal growth in all directions is ensured. The newly formed bony trabecular are not reabsorbed as in diaphysis, but remain giving to epiphysis a spongy appearance. The periosteal sleeve extends throughout the diaphysis and increases in thickness, which allows the increase in thickness and width of the long bones, while the growth in length mainly depends by endochondral ossification of the metaphysis. Then the compact bone, which forms the wall of the diaphysis, in the adult is formed almost exclusively for perichondral ossification first and then periosteal; while the spongy bone that forms the epiphysis is formed exclusively for endochondral ossification.
The regulatory factors of bone remodeling are:
In the bone tissue promotes the release of calcium by stimulating the activity of the osteoclasts; in renal tubules it reduces the reabsorption of phosphate and increases that of calcium; it promotes the activity of Vitamin D thus increasing the intestinal absorption of calcium.
It inhibits the activity of osteoclasts, promotes urinary elimination and the deposition of calcium in bone tissue, leading to a decrease in plasma levels of calcium, action opposite to that exerted by Vitamin D.
It promotes intestinal absorption of calcium (PTH-induced)
It is involved in elongation of bones because it controls the thickness of the growth plate
It stabilizes the triple helix of collagen.
The factors that instead interfere with the process of bone remodeling are:
Bone remodeling
After birth in both epiphyses appear the Epiphyseal or Secondary Ossification Centers, in which will be the endochondral ossification. In the epiphysis, when the cartilage cells proliferate give rise to cells that are arranged to form groups or nests, so that an epiphyseal growth in all directions is ensured. The newly formed bony trabecular are not reabsorbed as in diaphysis, but remain giving to epiphysis a spongy appearance. The periosteal sleeve extends throughout the diaphysis and increases in thickness, which allows the increase in thickness and width of the long bones, while the growth in length mainly depends by endochondral ossification of the metaphysis. Then the compact bone, which forms the wall of the diaphysis, in the adult is formed almost exclusively for perichondral ossification first and then periosteal; while the spongy bone that forms the epiphysis is formed exclusively for endochondral ossification.
When a bone undergoes a fracture, the fragments are removed by macrophages and the wound is filled with granulation tissue, whose cells are recruited in the periosteum and endosteum. This granulation tissue acts as a blastema and generates bone replacement. In a first time in the granulation tissue differentiate some chondroblasts that produce a fibrocartilagineous callus that closes the lesion. In this callus a interwoven bone is formed, because of endochondral ossification inside and subperiosteal deposition at the periphery.
At first are formed trabecular bone which then combine with healthy bone over callus. While the ossification goes on, the fibrocartilaginous callus is replaced by a interwoven bony callus quickly replaced by osteons of mature bone. The phenomenon of remodeling ensures that the new bone tissue is arranged in the most efficient way to withstand the stresses to which it is subjected.
The replacement is more rapid when the damaged surfaces of the fractured bone are aligned properly and when the bone loss is modest. This limits the need for formation of the callus and reduces the need of remodeling.
The repair of bone tissue is a spontaneous physiological process favored by the natural spontaneous and constant turnover of the constituents. Depending on the conditions in which the body is during the reparative phase of the bone, it may be useful to integrate the diet with a supplement able to provide the body with nutrients essential for bone metabolism and in particular for the reparative process, for the reabsorption of any hematoma, for the densely vascularized and innervated periosteum and endosteal vessels.
Sanità