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Bone tissue is a specialized form of connective tissue and is the main element of the skeletal tissues. It is composed of cells and a calcified extracellular matrix, in which stabilizing fibers are embedded. Bone is a rather unique tissue that performs several functions in addition to contributing to body shape and form. It is the major attachment site for tendons and muscles, essential for locomotion and other movements of the body. In some parts of the body, bones also provide the protective structures for vital tissues, such as brain, heart, lung,

corresponding anions, mainly calcium and phosphate, and as such is intimately involved in the mineral homeostasis of the body. In addition, the bone marrow is the place where most of the blood components, such as blood or immune cells, are formed. Finally, there are also mineralized tissues that have very specialized functions, such as for example the bones of the inner ear, which are responsible for the transmission of sound. The actual composition of bone varies strongly with age, anatomical location, and the general health and nutritional state. In general, the bone mineral accounts for about 50-70% of adult bone mass, the organic matrix for about 20-40%, water for about 5-10% and embedded lipids for about 1-5% [95-97].

Bone in human and other mammalian bodies is generally classified into two types. The dense outer shell is termed “cortical bone”, and is also known as compact bone. The inside contains a much finer network of bone, which more resembles a sponge, and is termed spongy or cancellous bone. Cortical bone is much denser with a porosity ranging between 5% and 10% and is found primarily in the shaft of long bones, but it also forms the outer shell around cancellous bone at the end of joints and in the vertebrae as shown in Figure 2 [97,98].

Bone has the ability to repair itself without leaving behind scar tissue. It also rapidly removes and replaces mineral storage based on metabolic demand, and it structurally reshapes in response to alterations in the mechanical stimului (e.g. following fractures or degenerative diseases). Four distinct cell types are responsible for carrying out the local formation, resorption, and maintenance of bone. These are osteoblasts, osteoclasts, osteocytes and the bone lining cells. Osteoblasts are the cells that synthesize the bone matrix and participate in bone mineralization. The functions of osteoblasts are influenced by a number of endocrine and cytokine mediators such as parathyroid hormone, prostaglandins, estrogens, vitamin D and some cytokines. Osteoclasts on the other hand, are multinucleated giant cells mainly responsible for resorption of bone, which also takes place during regular remodelling of the bone tissue. There are numerous factors that play a role in the regulation of osteoclast functions and bone resorption, which include parathyroid hormone (PTH), PTH related peptide, calcitonin, glucocorticoids, vitamin D, prolactin, interleukine-1 (IL-1), interleukine-6 (IL-6), tumor necrosis factor (TNF), prostaglandins, interferon-gamma, and members of the transforming growth factors beta superfamily, including bone morphogenetic proteins and others. Osteocytes are cells, which are buried within mature bone and are formed from osteoblasts that have been entrapped during bone formation. Several important roles are attributed to these cells, one of the most important being the maintenance of mineral homeostasis by permitting the diffusion of fluids and minerals through the cannicular system.

Osteocytes may also serve as a mechanical damage sensor responsible for initiating bone

remodelling or repair. Finally, the bone lining cells are formed by inactivation of osteoblasts or perhaps other mesenchymal type cells and they are mainly present on the surfaces of adult bone. The role of bone lining cells includes the partitioning of bone fluid compartment from interstitial fluids, the nutritional and metabolic support of osteocytes, and the initiation of osteoclast mediated resorption of bone [96,97,99-102].

Figure 2: Diagram represents the structure of different types of bone.

Besides the metabolically active cellular portion of bone, it also contains the non-living but very important bone matrix. It is the major constituent of bone and it is a well organized composite material consisting of an organic and an inorganic component [103].

About 90% of the organic matrix of bone is composed of type I collagen, which is synthesized by the osteoblasts and deposited in distinct layers known as lamellae in mature bones. The organic component of the matrix gives the bone its outer shape and contributes to its ability to resist tensional load. Bone also contains a variety of noncollagenous proteins that may be important in the organization of the matrix, the mineralization of the bone, and the behavior of the bone cells. These proteins include osteocalcin, osteonectin, bone sialoprotein, bone

different growth factors that can influence the function of bone cells and thereby regulation the function of this tissue [97,98].

The inorganic matrix, or mineral phase of bone, constitutes about 75% of the bone tissue mass and it is composed principally of calcium ions and phosphate, which are combined to form specific hydroxyapatite crystals of the composition [Ca10(PO4)6(OH)2]]]]. The hydroxyapatite in bone consists of very small crystals and contains many minute impurities, including carbonate or magnesium. Bone apatite is usually referred to as a “poorly crystalline, carbonate-substituted apatite” because of the impurities in the crystals, which are important in rendering bone apatite more soluble, thus permitting the apatite to release ions when needed for homeostasis or for the remodeling of bone [104]. The inorganic matrix of bone performs two essential functions: it serves as ion reservoir, and it gives bone most of its stiffness and strength. Approximately 99% of the body calcium, approximately 85% of the phosphorous and between 40% and 60% of the total body sodium and magnesium are associated with the bone mineral crystals [97].