2.1. Structure, function and physiology of bone

Bone is a specialized connective tissue with a mineralized extracellular matrix that functions to provide support, form and rigidity for the human skeleton and supplies a vast store of calcium necessary for calcium related homeostasis (Roberts et al. 1987, Gielinski & Marks 1994, Buckwalter et al. 1995a, Buckwalter et al. 1995b, Hansen et al. 1996, Whybro et al. 1998). Fossil records date the evolution of bone to the Paleozoic era some 300 million years ago. Since then bone has evolved to play a significant role in the vertebrate (Bourne 1976).

Embryologically, bone is formed by two separate developmental processes described as intramembranous and endochondral ossification (Craft & Sargent 1989, Bortell et al. 1990). When ossification has occurred directly, it is classified as being intramembranous in character. Embryonic mesenchymal cells with an abundant vascular supply develop loci of intracellular collagen deposition. Osteoblasts begin secreting osteoid into which calcium salts are deposited. Such direct bone formation is responsible for the genesis of the cranial vault, the facial skeleton and parts of the mandible, scapula and clavicle. Endochondral bone formation, involves a cartilaginous phase, where embryonic mesenchymal stem cells differentiate into a primitive hyaline cartilage. Blood vessels and bone forming units resorb the cartilage and replace it with osteoid while invading this matrix. Weight-bearing bones and those terminating in joints comprise most of this group of bones. In addition, most of the cranial base and a portion of the mandible are thought to have an endochondral origin (Frost & Jee 1994).

Irrespective of embryonic origin, bone is composed of four cellular types; osteoblasts, osteocytes, osteoclasts and bone lining cells (Marks & Poppof 1988). Osteoblasts are cuboidal cells having a prominent Golgi apparatus and well-developed rough endoplasmic reticulum, a histological sign of protein production. These fully differentiated cells secrete both the type I collagen and the non-collagenous proteins of bone"s organic matrix. They will also regulate the mineralization of this matrix. The osteocyte is thought to be a mature osteoblast that becomes trapped within the bone matrix. While their primary function is maintenance, they have demonstrated abilities to both synthesize and resorb bone (Martin & Ng 1994). Bone lining cells are flat, fusiform cells that are found covering inactive bone surfaces. Little is known about the function of these cells; however they may be precursors of osteoblasts. It is understood that certain cells (osteoprogenitor cells) are programmed to become bone cells and their origin is believed to lie with the primitive mesenchymal stem cells (Drivadahl et al. 1981). Osteoclasts, unlike the other bone cells, which have local origins, arise from the fusion of mononuclear precursor cells originating in the hematopoietic tissues. They function to resorb bone. Histologically, they have been characterized as having a ruffled border, where bone resorption is thought to occur. Coupling describes a process, which combines all of the above elements, whereby bone formation and resorption are maintained in balance (Farley et al. 1982). Once this balance is disrupted, excessive osteoclastic activity may lead to problems such as osteoporosis whereas increased osteoblastic activity may reflect bone growth, healing or pathological responses.

The architecture of bone is such that the outer shell of bone, referred to as cortical or compact bone, provides the mechanical support. It is composed of concentric sheets of collagen fibrils in the form of lamellar bone. Metabolic functions of bone are controlled by the centrally located cancellous, trabecular or spongy bone. In contrast to the densely packed fibrils of the cortical bone, the matrix of cancellous bone is loosely organized. Macroscopically, this bone appears as a honeycomb lattice in which hematopoietic elements are located. Bone is composed of 65–70% crystalline salts by weight, primarily in the form of hydroxyapatite, with the remaining 30–35% being composed of organic matrix. The organic matrix consists primarily of type I collagen (90–95%) interspersed with non-collagenous proteins such as osteopontin, osteonectin, and various growth factors (Robey et al. 1993).