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Ossification of Bone

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The process of human formation starts once the sperm fertilizes the ovum. The fertilized ovum usually contains both the female and male nuclei called pronuclei. After fertilization, cleavage occurs to form two cells. A zygote is the fertilized egg before the process of cleavage. Once fertilized, the egg undergoes a period of gestation in the womb that takes about 266 days before delivery (Marseken & Surhone).

Once cleavage begins, it goes on to form many cells. These cells undergo specialization to form various tissues. The tissues in turn form organs. The embryo is the developing baby between the first cleavage and the time when all main organs of the body form. The embryonic period is 56 days or eight weeks. After this period, the embryo becomes a fetus. The remaining 38 weeks, until birth, is the fetal period. Most of the fetal skeleton consists of cartilage. Cartilage has no minerals or salts (Marseken & Surhone).

The skeletal system is one of the vital systems in the human body. It consists of large bones and small bones. Large bone in the body includes the sternum, the cranial sutures, the pelvis, the radius and ulna. These bones take a long time to mature. A mature bone is a hard and compact living tissue. It consists of a dense layer of small structural units made up of both organic components such as fibroblasts, collagen, proteins, extracellular matrix and living cells (Marseken & Surhone). It also consists of mineral constituents mainly calcium carbonate and hydroxyapatite.


The process of bone formation is long and immensely complicated. It is a particularly vital process in development of the human body. Ossification is the process of formation bone through the activities of bone forming cells called osteoblasts. These cells take calcium from blood and deposit the salts into the bone. Most bones ossify partly sometime before the time of birth (Henrikson, Gordon & Mazurkiewicz). In order to understand ossification, it is necessary to understand some of the various terms used in explaining this process.

Osteogenesis is the other name for ossification. Calcification is a related word but it does not mean the same. Calcification is the deposition of calcium salts in to the soft bone tissues in the process of bone formation. This process takes place with the aid of Vitamin D. absence of vitamin D leads to the formation of soft bone and Rickets. Calcification process goes on throughout life until the age of about 40 years when bone development ceases (Henrikson, Gordon & Mazurkiewicz).

The process of ossification or bone formation cuts across the embryonic, fetal period, infancy through to early adulthood. In the third month, bone formation centers start to appear. Long formation of long bones begins during this period. The fetal skeleton forms by the time the fetus is three months old.

Types of Ossification

The bones form from conversion of certain connective tissues. There are various tissues that can develop into bones. These determine the ossification type. Ossification process is of two types: endochondral and intramembraneous ossification. Bone synthesis involves intramembraneous ossification, endochodral ossification or a combination of both.

Intramembraneous ossification also called mesenchymal ossification occurs when embryonic cells of the mesoderm called mesenchyme transforms into bone. In other words, bones form from mesenchymal condensation. Mesoderm is the middle layer of the three layers of cells that form in the embryonic period. Mesenchyme cells are responsible for the formation of most of the connective tissues, skeletal tissues, visceral tissues as well as the blood tissues. Example of the bones derived from this ossification type is the bones of the skull (Henrikson, Gordon & Mazurkiewicz).

On the other hand, endochondral ossification also called intracartilageneous ossification occurs when calcification or deposition of calcium occurs in the preformed cartilage tissues. The bone develops from cartilage and gradually replaces the soft cartilage. Most skeletal bone formations in the body form through this process. It occurs when osteoblasts arise in certain regions of the cartilage. Osteoblasts are actively-dividing cells that form bones. They undergo development to form mature bone cells called osteocytes. Osteocytes embed in the bone matrix.Chondrification is the conversion of mesenchmal condensations in cartilage. This process starts occurring during the second month of gestation (Martini, et al.). Membrane bones start ossification before the second month while cartilaginous bones begin ossifying after the second month (Martini, et al.).

A combination of endochondral and intramembraneous ossification also occurs and is responsible for the formation of most bones. This process starts by the first formation of chondroblast cells from mesenchyme cells. Division of chondroblasts occurs to increase in the number. The resultant cells increase in size and produce extracellular matrix of the cartilage. The matrix eventually hardens leaving small cavities or depressions called lacunae within the matrix. Blood forming cells and osteoblasts fill this lacuna. Osteoblasts are responsible for the formation of bone matrix that makes the bone hard and rigid.

Centers of Ossification

This process does not just start anywhere. There are certain points where ossification starts. The osteoblasts begin the activities of laying down the lamellae (the thin bands of calcium filled matrix usually arranged concentrically around a haversian canal) at these sites. These points are the centers of ossifications. Osteoblasts secrete the principal bone protein constituent called collagen as well as other substances that constitute the bone. There are two centers of ossification: primary and secondary centers. Primary centers appear in the fetal period while secondary centers appear after delivery.

The radius usually has three ossification centers: one on the shaft and others on the heads of the bones. The first center of ossification to appear is the one on the shaft. It begins at around the end of the second month. One year after birth, ossification begins on the lower epiphysis while the upper center of ossification appears at about five years. Lengthening may go on until the age of sixteen years when ossification starts to cease.

The ossification of the ulna is slightly different. Just like the radius it has three centers of ossification: on the olecranon, at the center and the exterior end. Intramembraneous ossification takes place in the center and starts at about eighth week. The olecranon and the inferior extremity are both cartilaginous at birth. Ossification center appears near the styloid process and spreads. The olecranon starts ossifying at ten years while the inferior extremity begins at about sixteen.

The sternum develops through mesenchymal ossification to form two cartilaginous bars. After fusing, the two bars develop eight centers of ossifications. The first appears at six months of pregnancy, second in the seventh month, the last appears at the eighteenth year. Ossification may go on up to 40 years, but usually it is complete by 25 (Henrikson, Gordon & Mazurkiewicz). Some parts remain unossified.

Ossification of the Cranial Sutures

The cranium undergoes ossification along cranial sutures. Both itramembraneous and endochondral ossification takes place distinctively. The neurocranium forms through mesenchymal ossification. The cranial base and the viscerocranium develop through intracartilaginous ossification. The membranous neurocranium has five centers of ossification, two frontal, two parietal and one occipital (Opperman 475).

The increase in brain volume provokes initiation of these centers. The flat bones grow radially against each other. The trabeculae thicken and cancellous bone becomes less porous than before forming compact bones. When there is a further development of compact bone and continues opposing of cranial bones, sutures form. A suture is an immovable joint in the cranium usually with little connective tissue between the frontal and parietal bones found (Opperman 473).

These sutures will provide intramembraneous growth sites. Increase in the cranial pressure due to the growth of brain lead to widening of cartilaginous growth sites and addition of cancellous bones on the edges. The sutures maintain the same distance between the developing bones. The sutures do not undergo ossification during the period of cranial expansion.

Ossification of sutures as well as closure of fontanelle (a cranial opening in a fetus or an infant that occurs due to the incomplete ossification) occurs since the brain is no longer exerting pressure on the cranium (Opperman 478). These occur when the brain ceases to grow and stops exerting pressure on the five centers of ossification. Despite the cessation of brain growth, the cartilaginous bones continue lying down of spongy bones that grow past each and forming a continuous flat bone (Opperman 478). The sutures lose their potency at this point. From this point, it is ineffective to carry out bone remodeling.

Premature ossification results in a permanent deformation of cranium. Rapid, premature fusion of the sutures leads to cranial asymmetry (Opperman 481). On the other hand, late ossification of cranial sutures results in sutural abnormalities and large fontanelle. Bone remodeling is the altering of bone structure of asymmetric or disproportionate skull to achieve symmetry. Orthotic modeling depends on ossification. If cranial sutures close due to early cessation of brain expansion, bone modeling is hard to achieve (Opperman 482).

Structure of a Long Bone

By studying the formation of long bones such as radius, one can understand the process of ossification. There are different classes of shape according to their shapes. These are flat bones, irregular bones, short bones and long bones. A mature long bone consists of a cylindrical shaft or body that has a marrow cavity within the compact bone called diaphysis. The end part called epiphysis has spongy bone covered with a shell of compact bone. These two parts develop separately. Immature long bone has the two parts separated by cartilage. This transitional cartilaginous region is the metaphysis. A thin membrane called periosteum covers and encloses the outer bone. Periosteum membrane supplies the bone with oxygen and nutrients as well as removes waste from the bones (Marseken & Surhone).

Compact bone is a dense, solidly filled (with mineral salts and organic compounds) bone matrix with small lacunae that have osteocytes. Osteocytes are mature osteoblasts are no longer involved in bone formation. Bone matrix consists of collagen fibers and crystalline salts bonded together (Marseken & Surhone). The minerals are calcium and phosphate salts. The matrix form concentric circles called Haversian systems. Haversian systems are also called osteons. Compact bones have small canals that ramify them called Haversian canal. A haversian canal forms a cylindrical surrounded by lamellae and cells-containing lacunae (Marseken & Surhone).

Lamellae is thin bands cancerous matrix usually arranged in concentric around a haversian canal. The lacunae in the compact bones forms links with each other through microscopic channels called canaliculi. Compact bone forms a thin coating around cancellous bone. Volkmann’s canals pass through and cross the Haversian systems allowing for circulation of all bone structures. Cancellous bone is the spongy-like, lattice-like bone usually within medullary cavity with a lot of space within it. It has a lower density than a compact bone.

Ossification Process of Long Bone

The process of ossification of long bones has  two stages: the early steps of ossification and the growth of epiphysis. In the first stage, intramembraneous ossification occurs to form the periosteal collar. A primary ossification center forms by the formation of matrix of diaphysis. The matrix undergoes erosion by blood vessel to form calcified spicules. Then bone forms from osteoblast cells on the calcified spicules. Finally, invasion of blood vessels initiates a secondary center of ossification (Marseken & Surhone).

The second phase of long bone formation involves the growths of the epiphysis. The development of the epiphysis plate takes place through various zones that occur in succession (Marseken & Surhone). First is the zone of reserve cells. These cells form a thin layer of chondrocytes next to the bony trabeculae. The second is the zone of proliferation where chondrocytes form in staked rows with a basophilic cartilage. There is a mitotic division of chondrocytes. The third zone is the zone of maturation that lacks chondrocyte mitosis, but has a gradual cellular enlargement.

Fourth is the zone of hypertrophy where there is an increase in the size of chondrocytes as well as the lacunae. The other one is the zone of calcification. Here, calcium salts deposit in the matrix around the lacunae. The result is the death of cells. The next is the zone of ossification. Osteoblasts secrete bone matrix on the calcified cartilage plates. Last is the zone of re-absorption where osteoclasts actively absorb bone spicules.

The bone increases in size up to the end of adolescence. In addition to increase in length, the body maintains the thickness and strength of the bone. Osteoclasts deposit new bone material while osteoclasts reabsorbs the old bone materials. The rates of deposition and absorption are the same. The net mass of the bone remains the same throughout.

Osteoclasts occur in small amounts but concentrated masses. They erode the bone for a short time and create a tunnel in the bone then cease their activity. They are succeeded by osteoclasts which deposit bone material for about a hundred days replacing the lost bone and filling the tunnel. Blood vessels signal cessation of osteoblasts activities once bone mass reaches it (Marseken & Surhone).

Ossification of different bones completes at different ages. At 25 years, ossification of all bones is complete. However, the alternating activities of osteoblasts and osteoclasts go on until the age of 40-45. A process of bone loss can occur if there is no replacement of calcium. The process of healing of bones at this stage is very slow.

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