Section through head of a femur, showing outer compact layer and soft trabecular center with red bone marrow and a spot of yellow bone marrow (white bar = 1cm)

Bone is not a uniformly solid material, but rather has some spaces between its hard elements.

Compact bone or (Cortical bone)

The hard outer layer of bones is composed of compact bone tissue, so-called due to its minimal gaps and spaces. This tissue gives bones their smooth, white, and solid appearance, and accounts for 80% of the total bone mass of an adult skeleton. Compact bone may also be referred to as dense bone.

Trabecular bone

Filling the interior of the organ is the trabecular bone tissue (an open cell porous network also called cancellous or spongy bone) which is composed of a network of rod- and plate-like elements that make the overall organ lighter and allowing room for blood vessels and marrow. Trabecular bone accounts for the remaining 20% of total bone mass, but has nearly ten times the surface area of compact bone.

Cellular structure

There are several types of cells constituting the bone;

• Osteoblasts are mononucleate bone-forming cells which descend from osteoprogenitor cells. They are located on the surface of osteoid seams and make a protein mixture known as osteoid, which mineralizes to become bone. Osteoid is primarily composed of Type I collagen. Osteoblasts also manufacture hormones, such as prostaglandins, to act on the bone itself. They robustly produce alkaline phosphatase, an enzyme that has a role in the mineralisation of bone, as well as many matrix proteins. Osteoblasts are the immature bone cells.

• Bone lining cells are essentially inactive osteoblasts. They cover all of the available bone surface and function as a barrier for certain ions.
• Osteocytes originate from osteoblasts which have migrated into and become trapped and surrounded by bone matrix which they themselves produce. The spaces which they occupy are known as lacunae. Osteocytes have many processes which reach out to meet osteoblasts and other osteocytes probably for the purposes of communication. Their functions include to varying degrees: formation of bone, matrix maintenance and calcium homeostasis. They have also been shown to act as mechano-sensory receptors—regulating the bone's response to stress and mechanical load. They are mature bone cells.

• Osteoclasts are the cells responsible for bone resorption (remodeling of bone to reduce its volume). Osteoclasts are large, multinucleated cells located on bone surfaces in what are called Howship's lacunae or resorption pits. These lacunae, or resorption pits, are left behind after the breakdown of the bone surface. Because the osteoclasts are derived from a monocyte stem-cell lineage, they are equipped with phagocytic like mechanisms similar to circulating macrophages. Osteoclasts mature and/or migrate to discrete bone surfaces. Upon arrival, active enzymes, such as tartrate resistant acid phosphatase, are secreted against the mineral substrate.

Molecular structure

Matrix

The matrix is the major constituent of bone, surrounding the cells. It has inorganic and organic parts.

Inorganic

The inorganic is mainly crystalline mineral salts and calcium, which is present in the form of hydroxyapatite. The matrix is initially laid down as unmineralised osteoid (manufactured by osteoblasts). Mineralisation involves osteoblasts secreting vesicles containing alkaline phosphatase. This cleaves the phosphate groups and acts as the foci for calcium and phosphate deposition. The vesicles then rupture and act as a centre for crystals to grow on.

Organic

The organic part of matrix is mainly composed of Type I collagen. This is synthesised intracellularly as tropocollagen and then exported, forming fibrils. The organic part is also composed of various growth factors, the functions of which are not fully known. These factors present include glycosaminoglycans, osteocalcin, osteonectin, bone sialo protein and Cell Attachment Factor. One of the main things that distinguishes the matrix of a bone from that of another cell is that the matrix in bone is hard.

Woven or lamellar

Collagen fibres of woven bone

Bone is first deposited as woven bone, in a disorganized structure with a high proportion of osteocytes in young and in healing injuries. Woven bone is weaker, with a small number of randomly oriented collagen fibers, but forms quickly. It is replaced by lamellar bone, which is highly organized in concentric sheets with a low proportion of osteocytes. Lamellar bone is stronger and filled with many collagen fibers parallel to other fibers in the same layer (these parallel columns are called osteons). The fibers run in opposite directions in alternating layers, much like plywood, assisting in the bone's ability to resist torsion forces. After a break, woven bone quickly forms and is gradually replaced by slow-growing lamellar bone on pre-existing calcified hyaline cartilage through a process known as "bony substitution."

Types

There are five types of bones in the human body: long, short, flat, irregular and sesamoid.

• Long bones are characterized by a shaft, the diaphysis, that is much greater in length than width. They are comprised mostly of compact bone and lesser amounts of marrow, which is located within the medullary cavity, and spongy bone. Most bones of the limbs, including those of the fingers and toes, are long bones. The exceptions are those of the wrist, ankle and kneecap.
• Short bones are roughly cube-shaped, and have only a thin layer of compact bone surrounding a spongy interior. The bones of the wrist and ankle are short bones, as are the sesamoid bones.
• Flat bones are thin and generally curved, with two parallel layers of compact bones sandwiching a layer of spongy bone. Most of the bones of the skull are flat bones, as is the sternum.
• Irregular bones do not fit into the above categories. They consist of thin layers of compact bone surrounding a spongy interior. As implied by the name, their shapes are irregular and complicated. The bones of the spine and hips are irregular bones.
• Sesamoid bones are bones embedded in tendons. Since they act to hold the tendon further away from the joint, the angle of the tendon is increased and thus the force of the muscle is increased. Examples of sesamoid bones are the patella and the pisiform.

Formation

The formation of bone during the fetal stage of development occurs by two processes: intramembranous and endochondral ossification.

Intramembranous ossification mainly occurs during formation of the flat bones of the skull; the bone is formed from mesenchyme tissue. The steps in intramembranous ossification are:

1. Development of ossification center
2. Calcification
3. Formation of trabeculae
4. Development of periosteum

Endochondral ossification

Endochondrial ossification

Endochondral ossification, on the other hand, occurs in long bones, such as limbs; the bone is formed from cartilage. The steps in endochondral ossification are:

1. Development of cartilage model
2. Growth of cartilage model
3. Development of the primary ossification center
4. Development of the secondary ossification center
5. Formation of articular cartilage and epiphyseal plate

Endochondral ossification begins with points in the cartilage called "primary ossification centers." They mostly appear during fetal development, though a few short bones begin their primary ossification after birth. They are responsible for the formation of the diaphyses of long bones, short bones and certain parts of irregular bones. Secondary ossification occurs after birth, and forms the epiphyses of long bones and the extremities of irregular and flat bones. The diaphysis and both epiphyses of a long bone are separated by a growing zone of cartilage (the epiphyseal plate). When the child reaches skeletal maturity (18 to 25 years of age), all of the cartilage is replaced by bone, fusing the diaphysis and both epiphyses together (epiphyseal closure).

Bone marrow

Bone marrow can be found in almost any bone that holds cancellous tissue. In newborns, all such bones are filled exclusively with red marrow , but as the child ages it is mostly replaced by yellow, or fatty marrow. In adults, red marrow is mostly found in the flat bones of the skull, the ribs, the vertebrae and pelvic bones.

Remodeling

Remodeling or bone turnover is the process of resorption followed by replacement of bone with little change in shape and occurs throughout a person's life. Osteoblasts and osteoclasts, coupled together via paracrine cell signalling, are referred to as bone remodeling units.

Purpose

The purpose of remodeling is to regulate calcium homeostasis, repair micro-damaged bones (from everyday stress) but also to shape and sculpture the skeleton during growth.

Calcium balance

The process of bone resorption by the osteoclasts releases stored calcium into the systemic circulation and is an important process in regulating calcium balance. As bone formation actively fixes circulating calcium in its mineral form, removing it from the bloodstream, resorption actively unfixes it thereby increasing circulating calcium levels. These processes occur in tandem at site-specific locations.

Repair

Repeated stress, such as weight-bearing exercise or bone healing, results in the bone thickening at the points of maximum stress (Wolff's law). It has been hypothesized that this is a result of bone's piezoelectric properties, which cause bone to generate small electrical potentials under stress.³

Paracrine cell signalling

The action of osteoblasts and osteoclasts are controlled by a number of chemical factors which either promote or inhibit the activity of the bone remodelling cells, controlling the rate at which bone is made, destroyed or changed in shape. The cells also use paracrine signalling to control the activity of each other.