Ossification or osteogenesis is the process of laying down new bone material by osteoblasts. It results in formation of bone tissue.
Normal bone ossification is of two tyoes –
- Endochondral ossification – A cartilage is formed as precursor on which new bone is laid down whereas
- Intramembranous ossification is the direct laying down of bone into the primitive connective tissue (mesenchyme). There is no intermediate cartilage involved.
[Mesenchymal cells are cells that have not been differentiated yet]
Fractures treated by plaster applications heal by endochondral ossification whereas fractures treated by open reduction and internal fixation heal by intramembranous ossification.
Bone ossification is not same as calcification. Calcification is the laying of calcium-based salts and crystals within cells and tissue. Calcification is a normal part of ossification but it also occurs in many pathologies.
Endochondral ossification is essential for the formation of long bones [bones like femur which are longer than wide] and the ends of flat and irregular bones[like ribs,vertebrae).
Endochondral ossification involved in natural growth and lengthening of bone. It is also involved in natural healing of bone fractures.
The primary endochondral ossification is distinguished from intramembranous ossification is the fact that cartilage is present during endochondral ossification.
Endochondral ossification is the formation of long bones and other bones which include a hyaline cartilage precursor.
Formation of long bones has two centers of ossification.
The first site of ossification occurs in the primary center of ossification, which is in the middle of diaphysis [shaft] and secondary center of ossification which appear around birth at both ends of long bones [epiphysis].
Endochondral Ossification at Primary Ossification Center
- In long bones, bone tissue first appears in the diaphysis
- Cartilage produced by chondrocytes is absorbed by osteoclasts and osteoblasts lay down the bone on cartilaginous framework [bone replaces cartilage, cartilage is not converted to bone] leading to formation of primary trabecular bone.
- Cartilage is progressively eroded and replaced by hardened bone, extending towards the epiphysis.
- Perichondrium layer surrounding the cartilage forms the periosteum which lays down bone to make a collar that encircles the outside of the bone.
- Osteoclasts, formed from macrophages, break down spongy bone to form the medullary (bone marrow) cavity.The osteoblasts are also responsible for appositional growth which increases girth of the bone.
Endochondral Ossification in Secondary center of ossification: The Process of Bone Growth
The process is similar to primary ossification center. After secondary ossification center appears in the physis, the unossified cartilage left between the primary and secondary ossification centers is called the epiphyseal plate. This cartilage plate is the key to form new cartilage, which is replaced by bone, a process that results in an increase in length of the bone. Growth continues until the cartilage in the plate is replaced by bone. The point of union of the primary and secondary ossification centers is called the epiphyseal line.
A section of the end of growing bone reveals following histology –
- Zone of resting cartilage – contains normal, resting hyaline cartilage.
- Zone of proliferation / cell columns – chondrocytes undergo rapid mitosis, leading to proliferation and form distinctive looking stacks.
- Zone of maturation / hypertrophy – Chondrocytes enlarge and begin to secrete alkaline phosphatase which triggers calcification
- Zone of calcification – Chondrocytes die as they do not receive nutrition leaving cavities that will later become invaded by bone-forming cells.
- Zone of ossification Osteoprogenitor cells invade the area and differentiate into osteoblasts, which elaborate matrix that becomes calcified on the surface of calcified cartilage.
Sox-9 and PTHrP are the transcritption factors involved in bone growth
Addition of more extracellular matrix on the peripheral cartilage surface, which is accompanied by new chondroblasts that develop from the perichondrium results in increase in thickness.
Endochondral Ossification in Fracture Healing
This is seen in casting, bracing and intramedullary nailing. These treatments allow for some motion at the fracture site.
Intramembranous ossification is type of bone ossification where the bone tissue is created directly over the mesenchymal tissue [and not on cartilage as in endochondral ossification]. It occurs in healing of bone fractures and the initial formation of the flat bones of our skull. This process is also responsible for forming our jaw and clavicles, or collar bones
Creation of bone tissue
- Mesenchymal stem cells within mesenchyme or the medullary cavity of a bone fracture initiate the process of intramembranous ossification.
- A small group of mesenchymal stem cells begin to replicate and form a cluster of cells, a nidus.
- Once a nidus has been formed the mesenchymal stem cells within it stop replicating.
- Morphological changes in the mesenchymal stem cells begin to occur and they turn intoosteoprogenitor cell. These changes are
- the cell body becomes larger and rounder
- the long, thin cell processes vanish
- Golgi apparatus and rough endoplasmic reticulum increase
- Osteoprogenitor cells also undergo morphological process to turn intoosteoblasts
- Shape becomes more columnar
- Amount of Golgi apparatus and rough endoplasmic reticulum increases.
- Osteoblasts create an extracellular matrix containing Type-I collagen [ osteoid.]. Some of the osteoblasts become incorporated within the osteoid to become osteocytes.
- Mineralization occurs resulting in bone tissue and bone spicules
- Further secretion of osteoid increases the size of spicules which fuse with each other and become trabeculae.
- With continuous growth, trabeculae become interconnected and woven bone is formed. The term primary spongiosa is also used to refer to the initial trabecular network.
- The periosteum is formed around the trabeculae
- Osteogenic cells that originate from the periosteum increase appositional growth and a bone collar is formed.
Eventually, woven bone is replaced by lamellar bone.
Following is a very good visual explanation of endochondral ossification.
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