Basic Bone Biology

Bone is a highly specialized support tissue which is characterized by its rigidity and hardness. The major functions of bone are:

to provide structural support for the body to provide protection of vital organs to provide an environment for marrow (both blood forming and fat storage) to act as a mineral reservoir for calcium homeostasis in the body

Bone is composed of:

support cells (osteoblasts and osteocytes) remodeling cells (osteoclasts) nonmineral matrix of collagen and noncollagenous proteins (osteoid) inorganic mineral salts deposited within the matrix

Bone Cells
Cells concerned with the production, maintenance and modeling of the osteoid are:

Osteoblasts: These cells are derived from mesenchymal stem cells and are responsible for bone matrix synthesis and its subsequent mineralization. In the adult skeleton, the majority of bone surfaces that are undergoing neither formation nor resorption (i.e., not being remodeled) are lined by bone lining cells (the inactive form of the osteoblast).

Osteocytes: These cells are osteoblasts that become incorporated within the newly formed osteoid which eventually becomes calcified bone. Osteocytes situated deep in bone matrix maintain contact with newly incorporated osteocytes in osteoid, and with osteoblasts and bone lining cells on the bone surfaces, through an extensive network of cell processes (canaliculi). They are thought to be ideally situated to respond to changes in physical forces upon bone and to transduce messages to the osteoblastic cells on the bone surface, directing them to initiate resorption or formation responses.

Osteoclasts: These cells are large multinucleated cells, like macrophages, derived from the hematopoietic lineage. Osteoclasts function in resorption of mineralized tissue and are found attached to the bone surface at sites of active bone resorption. Their characteristic feature is a ruffled edge where active resorption takes place with the secretion of bone-resorbing enzymes, which digest bone matrix.

Bone Matrix
Osteoid is comprised of type I collagen (~94%) and noncollagenous proteins. The hardness and rigidity of bone is due to the presence of mineral salt in the osteoid matrix, which is a crystalline complex of calcium and phosphate (hydroxyapatite). Calcified bone contains about 25% organic matrix (2-5% of which are cells), 5% water and 70% inorganic mineral (hydroxyapatite).

Structure
Most bones have a basic structure composed of:

an outer cortical or compact zone an inner trabecular or spongy zone a periosteum

an endosteum Cortical bone forms a rigid outer shell, which resists deformation, while the inner trabecular network provides strength by acting as a complex system of internal supports. Compact bone contains very few spaces and the layers of bone matrix are packed tightly together forming osteons (Haversian systems). The spaces between the trabecular meshwork are occupied by bone marrow. In bones with a substantial weight-bearing function, the trabecular pattern is arranged to provide maximum resistance to the physical stress to which that bone is normally subjected. Bones are covered by two membranes: (i) the periosteum consists of a dense fibrous membrane covering the surface of bones (except at their extremities), serves as an attachment for tendons and muscles, and contains nerves and blood vessels that nourish the enclosed bone; and (ii) the endosteum consists of a thin layer of vascular connective tissue lining the marrow cavity.

Types of Bone
Two types of bone can be identified according to the pattern of collagen forming the osteoid:

Woven bone is characterized by a haphazard organization of collagen fibers and is mechanically weak. Lamellar bone is characterized by a regular parallel alignment of collagen into sheets (lamellae) and is

mechanically strong. Woven bone is produced when osteoblasts produce osteoid rapidly. This occurs initially in all fetal bones, but the resulting woven bone is replaced by remodeling and the deposition of more resilient lamellar bone. In adults, woven bone is formed when there is very rapid new bone formation, as occurs in the repair of a fracture. Following a fracture, woven bone is remodeled and lamellar bone is deposited. Virtually all bone in the healthy mature adult is lamellar bone.

Bone Development and Growth

Osteogenesis occurs by two processes:

Intramembranous ossification involves the replacement of connective tissue membrane sheets with bone tissue and results in the formation of flat bones (e.g., skull, clavicle, mandible). Endochondral ossification involves the replacement of a hyaline cartilage model with bone tissue (e.g., femur, tibia, humerus, radius).

Long bones continue to grow in length and width throughout childhood and adolescence. Increase in length is due to continued endochondral bone formation at each end of the long bones. Increase in circumference of the bone shaft is achieved by formation of new bone on the outer surface of the cortical bone.

Bone Modeling
Modeling is when bone resorption and bone formation occur on separate surfaces (i.e., formation and resorption are not coupled). An example of this process is during long bone increases in length and diameter. Bone modeling occurs during birth to adulthood and is responsible for gain in skeletal mass and changes in skeletal form.

Bone Remodeling
Remodeling is the replacement of old bone tissue by new bone tissue which mainly occurs in the adult skeleton to maintain bone mass. This process involves the coupling of bone formation and bone resorption and consists of five phases: 1. 2. 3. 4. 5. activation: preosteoclasts are stimulated and differentiate under the influence of cytokines and growth factors into mature active osteoclasts resorption: osteoclasts digest mineral matrix (old bone) reversal: end of resorption formation: osteoblasts synthesize new bone matrix quiescence: osteoblasts become resting bone lining cells on the newly formed bone surface