Bone

Bone is one of the hardest tissues of the human body and is second only to cartilage in its ability to withstand stress. As the main constituent of the skeleton, it supports fleshy structures, protects vital organs (such as those in the cranial and thoracic cavities) and also contains marrow, where the blood cells are formed.

Besides these three functions, bones form a system of levers which multiply the forces generated during muscle contraction, transforming them into body movements.

Bone is composed of intercellular calcified material, the bone matrix and different cell types.

 1) Osteocytes which are found in cavities (lacuna) within the matrix

 2) Osteoblasts which synthesize the organic components of the matrix

 3) Osteoclasts which are multinucleated giant cells involved in the resorption of bone tissue,  thus participating in the bone remodeling process

Internal and external surfaces of bones are covered by layers of connective tissue named endosteum and periosteum. Bone surfaces not covered by connective tissue or by osteoblasts are subject to resorption through the activity of osteoclasts which appear in the region. For this reason, special attention is given to the periosteum and endosteum during surgery.

The periosteum is a layer of dense connective tissue that is very fibrous externally but more cellular and vascular near the bone tissue.

Periosteal collagenous fibers are called Sharpey's fibers. They bind the periosteum to the underlying bone tissue.

Periosteal cells with morphologic characteristics of fibroblasts are easily transformed into osteoblasts and then, through mitosis, into other osteoblasts. These periosteal cells play a prominent role in bone growth and repair.

The endosteum has the same components as the periosteum and nearly the same structure, but it is considerably thinner, and does not have two layers as the periosteum does.
 

Long bones - form the extremities

Have a shaft known as the diaphysis. It is almost totally composed of compact bone with a small component of spongy bone in an inner position around the marrow cavity. On the ends of the shaft we find the epiphyses, which are spongy bone covered with a thin layer of compact bone.

Flat bones

form the calvarium (or skull), there are two layers of compact bone called plates, with a layer of spongy bone (called diploe) in between.

Histologically there are two types of bone tissue.
 1) primary (immature or woven bone)
 2) secondary (mature or lamellar bone)

Primary bone

is the first bone tissue to appear both in formation and repair. It is temporary and is replaced in adults by secondary bone, except near the sutures of the flat bones of the skull, in tooth sockets, and in the insertions of some tendons.

Secondary (in adults)

has collagenous fibers arranged in concentric lamella organized around a vascular canal.

The whole complex of concentric lamellae surrounding a canal containing blood vessels, nerves, and loose connective tissue is called the Haversian system.

Each Haversian system is a long, often bifurcated cylinder parallel to the diaphyses. It consists of a central canal (of Havers) surrounded by 4 - 20 concentric lamellae. These Haversian canals communicate with the marrow cavity, with the periosteum, and with each other through transverse or oblique canals called Volkmann's canals

The osteocytes found within lacuna communicate with each other via canaliculi.

Formation of bone

Bone tissue is formed by either intermembranous ossification or by endochondral ossification. In either case the bone tissue which appears first is primary or immature bone.

 Intramembranous Ossification

is so named because it takes place within membranes of connective tissue.

the frontal, parietal, parts of the occipital and temporal bones of the skull and the mandible and maxilla are formed by intramembranous ossification.

In the connective tissue the starting point is called the primary ossification center. The process begins when cells resembling young fibroblasts differentiate into osteoblasts. Osteo synthesis and calcification follow, surrounding some osteoblasts which then become osteocytes. This happens in several groups so that the fusion of the matrix spicules gives a spongy structure.

Endochondral Ossification

Takes place over a piece of hyaline cartilage (hence the name) whose shape resembles a small model of the bone to be formed.

principally forms the long bones and short bones

Basically endochondral ossification consists of 2 processes. The first process is hypertrophy and destruction of the chondrocytes of the model of the bone, leaving cavities separated by the septa of a calcified cartilage matrix. In the second process, undifferentiated mesenchymal cells and blood capillaries penetrate into the spaces left by the destroyed chondrocytes. The undifferentiated cells give rise to osteoblasts which form an osseous matrix on the remnants of the calcified cartilage matrix. In this way, bone tissue appears at the site where there was cartilage, but there is no transformation of cartilage into bone tissue.

1° Ossification Center

In the diaphyses of a long bone the first bone tissue to form appears by intramembranous ossification at the
perichondrium surrounding the diaphyses. This produces a bone collar about the diaphyses. The cartilage cells of this cartilage model below the bony collar increase their size and degenerate, leaving large cavities. The cartilage matrix becomes reduced to slender calcified partitions. Osteoclasts in the bone collar make holes through which blood vessels from the periosteum can enter the matrix. Along with these vessels undifferentiated mesenchymal cells also invade the area, these proliferate and give rise to osteoblasts and bone marrow stem cells. These form a continuous layer over the calcified cartilaginous matrix and start to synthesize bone matrix.
 
A secondary ossification center arises at each epiphyses. The function of these centers is similar to the 1° centers but the growth is radial rather than longitudinal. (no bone collar formed since articular cartilage does not have a perichondrium)

Epiphyseal plate

is a cartilaginous disk that is replaced continuously by expanding bone mainly from the diaphyseal center. It connects the epiphyses to the diaphyses. No further longitudinal growth can take place after epiphyseal cartilage is replaced by bone tissue.

Epiphyseal cartilage is divided into 5 zones

 1) resting zone - hyaline cartilage

 2) Proliferative zone - chondrocytes divide rapidly and form parallel rows of stacked cells along  the long axis of the bone

 3) Zone of Hypertrophy - large chondrocytes whose cytoplasm has accumulated glycogen. The  matrix is reduced to thin septa between the chondrocytes

 4) Zone of Calcification - death of chondrocytes, thin septa of cartilage become calcified by  deposition of hydroxyappatite

 5) Zone of Ossification - bone tissue appears

Fracture repair

When a bone is fractured, the damage suffered by the blood vessels produces a localized hemorrhage with the formation of a blood clot. Destruction of bone matrix and death of bone cells adjoining the fracture also occur.

During repair, the blood clot, the remaining cells, and the damaged bone matrix are removed. The periosteum and endosteum around the fracture respond with intense proliferation of their fibroblasts and other undifferentiated cells which form a cellular tissue surrounding the fracture, and penetrate between the extremities of the fractured bone. Some of these cells differentiate into macrophages which engulf the remains of the damaged tissue and the blood clot.
 
Immature bone is then formed by endochondal ossification of small fragments of cartilage appearing in the connective tissue that develops first in the fracture. It is also formed by means of intramembranous ossification. Therefore, areas of cartilage, areas of intramembranous ossification, and areas of endochondral ossification are encountered simultaneously when repair is taking place. Repair progresses in such a way that, after a period of time, irregularly formed trabeculae of immature bone temporarily unite the extremities of the fractured bone forming a bone callus.

Normal stress imposed on the bone during repair and during the patients gradual return to activity serves to remodel the bone callus. the remodeling of the bone callus reconstitutes the bone as it was prior to fracture. The primary bone tissue of the callus is gradually resorbed and replaced by lamellar bone, resulting in restoration of the original bone structure.

Plasticity of bone

Bone is capable of remodeling its internal structure according to the different stresses to which it is subjected. This is how orthodontic appliances (braces) work. Bone formation takes place on the side where traction is applied and is resorbed on the side when pressure is exerted (the opposite side).

Calcium reserve

The skeleton contains 99% of the bodies calcium and acts as a calcium reservoir. The concentration of calcium in the blood and tissue is held quite stable, this means that calcium taken in through the diet usually goes into storage in the bones or is excreted in the feces and urine.

Calcium can be mobilized from the bone in 2 ways

 1) a simple transfer of ions from hydroxyapatite crystals to interstitial fluid, where calcium can  pass quickly into the blood.

 2) Requires parathyroid hormone - this hormone activates and increases the number of cells  promoting resorption (osteoclasts) of the bone matrix, with the consequent liberation of calcium.

Calcitonin (produced in the thyroid) inhibits matrix resorption and calcium mobilization. Thus its action is the opposite of parathyroid hormone.
 
Nutrition

Calcium deficiency may be due to lack of calcium in the diet or the lack of vitamin D which is important for the absorption of calcium by the small intestine.

Calcium deficiency in children results in rickets

Calcium deficiency in adults results in osteomalacia This condition may be evident during pregnancy since the developing fetus requires a great deal of calcium.

Vitamin A also plays a role in balancing the production and resorption of bone. Deficiency of vitamin a results in osteoblasts not synthesizing the bone matrix normally, thus the individual may not reach their normal stature.

Vitamin C is essential for the production of collagen by cells including osteoblasts. Deficiency interferes with bone growth and hinders repair of fractures.

Hormones

Growth hormone from the anterior lobe of the pituitary stimulates overall growth. Lack of growth hormone during the growing years results in pituitary dwarfism. Excess growth hormone during the growing years causes gigantism due to excess growth in the long bones. In adults, since long bones can no longer increase in length (no epiphyseal cartilage) they increase in width by periosteal growth. This causes acromegaly.

Sex hormones both male and female have very complex effects on bone growth, but are, in general, stimulators of bone growth.