Bone is a complex tissue made up of cells and extra cellular organic and mineral material. The cells are of a wide variety of morphological and functional types, but all have a common origin in the mesenchymal stem cells. The principal cell types are: (i) chondrocytes or cartilage cells, which secrete the collagen matrix of the cartilage region; (ii) osteoblasts or bone-forming cells; (iii) osteoclasts, which are multinucleated giant cells responsible for bone resorption; and (iv) osteocytes, individual functional osteoblasts that are trapped in the mineralized bone matrix. On a dry weight basis, bone consists of 65–70% inorganic crystals of calcium hydroxyapatite and 30–35% organic matrix known as osteoid. Of the osteoid, 40% is composed of the extra cellular protein collagen.
There are two major categories of bone which are differentiated on the basis of density; these are the cortical bone and the trabecular or cancellous bone. See Figure1, which illustrates an interface region with both cortical and cancellous bone. Cortical bone is composed of densely packed columns of mineralized collagen laid down in layers and is the major component of tubular bones. Cortical bone accounts for 80% of the total bone mass of an adult and has a total area of ~3.2 m2. Examples of cortical bone are the femur and tibia of the leg, and humerus and radius of the arm. Trabecular or cancellous bone is spongy in appearance, providing both strength and elasticity, and is present in the spinal vertebrae, thin bones (the skull), and the ends of long bones (e.g., the hip bones). Trabecular bone accounts for 20% of the total bone mass of an adult but has ~16 meters2 or 5× times the surface area of cortical bone.
Fig1. Schematic representation of the main features of the structure of bone. This presentation illustrates both the transverse (top) and longitudinal sections of an interface region between both cortical and cancellous or spongy bone. Osteons are the fundamental building blocks of cortical bone. Bone is comprised of concentric layers of osteons along the long axis longitudinally from the top to the bottom of a long bone. Each osteon consists of concentric layers of lamellae of compact bone tissue that consist of parallel layers of collagen sheets that surround a central canal, the Haversian canal. Haversian canals are tiny, interconnecting, parallel channels along the long axis of the bone tissue through which a blood capillary and a nerve pass. Volkmann’s canals are small channels that transmit blood vessels from the periosteum (a membranous outer layer of bone) into the bone; they lie perpendicular to the Haversian canals and their capillaries connect with the capillaries of the Haversian canals. Lacunae cavities lie between the lamellae and are connected to one another by a series of small canals termed canaliculae. Each lacuna is occupied by one osteocyte (see also Figure 2). The periosteum is a membrane that lines the outer surface of all bones, except at joints and provides nourishment for the bone via its capillaries.
Fig2. Role of osteoblasts and osteocytes. Osteoblasts secrete the organic matrix of bone (termed osteoid). The osteoid is principally collagen fibers (see Figure 3) and two other bone proteins, osteonectin and osteopontin. As a consequence of mineralization of the osteoid, each osteoblast becomes surrounded with calcified bone matrix and then becomes converted to an osteocyte. The isolated osteocytes communicate with one another via their cell process, the tiny canaliculus.
Fig3. A schematic summary of the integrated intracellular and extracellular ten steps involved in the biosynthesis of a collagen fiber. The first five steps occur inside the cell starting with the biosynthesis of a collagen pro-α-chain. This is followed by hydroxylation of selected lysines and prolines and then glycosylation of selected prolines and lysines. Then the pro-α-chains self-assemble into a procollagen triple helix which is secreted from the osteoblast. The procollagen molecule is next subject to selective protease cleavage to yield a mature collagen molecule which then self assembles into a mature collagen fiber. These collagen fibers along with other bone proteins (osteocalcin, osteopontin) are the organic matrix that then becomes mineralized with precipitated calcium hydroxyapatite, yielding a solid bone.
The formation of functional bone tissue can be divided into two phases: (i) that is concerned with the production and secretion of the extracellular collagen bone matrix; and (ii) the deposition of the mineral calcium hydroxyapatite crystals in and around the matrix. It should be emphasized that bone is a dynamic tissue and that both of these processes occur on a minute-by minute basis throughout the life of the skeletal system.
Neither the collagen matrix, the extracellular mineral crystals, nor the several different cell types associated with bone exclusively determine the behavior of the bone tissue. It is a unique combination of the extracellular proteins and the inorganic phases, as well as the particular biochemical properties of the various bone cell types, that collectively confers on bone both its unusual mechanical properties (to support the weight of the soft tissues of the body) and its ability to serve as a dynamic reservoir for the calcium and phosphate ions needed for mineral homeostasis in the whole organism.
Bone matrix is biosynthesized, secreted, organized, mineralized, and finally destroyed by reabsorption, all in accordance with the local physiological and hormonal signals operative at any particular time. The production of organic matrix by osteoblast cells first involves the intracellular synthesis of protocollagen molecules by the ribosomal system through conventional protein biosynthetic pathways. A schematic summary of collagen biosynthesis and conversion to functional three-stranded cross-linked collagen fibrils is summarized in Figure 3. Each collagen strand of the fibrils has its separate unique amino acid sequence and is glycosylated. The collagen fibrils then become impregnated with the calcium hydroxyapatite that is the precipitated form of [Ca2+10(PO43−)6(OH−)2].
In the normal process of human bone formation, there is usually a delay of 5–10 days between the synthesis of the extracellular organic matrix and its ultimate mineralization. After the final secretion of protocollagen by the osteoblasts and the ultimate formation of mature collagen, the osteoblasts differentiate and are incorporated into the bone matrix as osteocytes (see Figure 2). On average, the skeletal system receives 13–18% of the total cardiovascular output. Given that every day approximately 300 mg of calcium and 160 mg of phosphorus are resorbed from the skeleton and replaced from the circulatory system, then approximately every 10 years all the skeletal calcium and phosphate have been completely replaced.
