Endochondral Ossification

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Endochondral Ossification

Endochondral ossification is a complex process compared to intramembranous ossification.  Endochondral ossification introduces us to a lot of new vocabulary.  Similar to intramembranous ossification, we have to start out with a model of the bone.  instead of starting with a sheet of dense connective tissue, the model is a hyaline cartilage model. It is made by chondrocytes, rather than the mesenchymal cells that create the model in intramembranous ossification.  Because cartilage is not a vascularized tissue, oxygen and glucose cannot reach the chondrocytes at the center of the model. These chondrocytes are cut off.   They begin to die, leaving their lacunae empty.  This results in a multitude of tiny holes in the cartilage model.  Osteoblasts at the outer edges of the hyaline cartilage model begin to secrete bone. 

This forms the bone collar. It is a layer of compact bone. This layer is along the outer edges of almost all bones in your body.  This collar provides support to the elongating bone. It functions much like a collar of a shirt, which can be starched to support a specific shape.  The osteoblasts at the outer edges begin the formation of the inner cellular layer of the periosteum. This separates the hyaline cartilage model from the surrounding tissues.  As all this happens, blood vessels are coming close periosteum and even perforating it in certain places.  When the blood vessels finally vascularize the center of the diaphysis, they form our first ossification center. It is called the primary ossification center.  At the ossification center, osteoblasts are secreting osteoid and the matrix of the bone is mineralized with calcium. 

Slowly, the osteoblasts in the primary ossification center replace the cartilage of the diaphysis with bone.  This primary ossification center will ultimately turn into the medullary cavity. This cavity contains the adipose connective tissue of the bone marrow.


Endochondral Ossification

As osteoclasts begin forming the medullary cavity, the bone becomes more vascularized. Perforating canals run transverse, and the central canals of each osteon contribute to this vascularization.  An area referred to as the metaphysis forms.  This is the area where chondrocytes still remain and are creating cartilage via appositional growth, or growth at the edge.  As they create more cartilage on the border of the diaphysis, the developing epiphysis moves away from the diaphysis. This movement elongates the bone.  Spicules, something like the stalactites and stalagmites of caverns and caves, stick out into the medullary cavity of the diaphysis.  Here, osteoblasts are turning that newly formed cartilage into bone tissue. 

As the chondrocytes move away from the diaphysis, the osteoblasts actively chase them. They lay down bone to replace the hyaline cartilage.  The final steps of ossification occur with even more vascularization of the bone.  This time, these are called secondary ossification centers and are located in both the proximal and distal epiphyses. I feel like these last two diagram skip a bunch of steps between them.  To form these centers, chondrocytes have to die. Osteoblasts have to replace the cartilage with bone. Finally, osteoclasts will create the spongy bone and ossification centers. 


The Epiphyseal Plate

Activity at the metaphysis continues after birth.  This ever-expanding region is called the epiphyseal plate or growth plates.  While the chondrocytes are still active, they push themselves away from the diaphysis to elongate the bone. During this time, these plates are referred to as “open” or “active.”  This means that the bones are still growing, or elongating. 

This histological inset here is of the epiphyseal plate.  At the top of the slide, we can see the hyaline cartilage. It has its characteristic look of chondrocytes in lacunae. The matrix has a glassy background.  That blue swath there is a bunch of chondrocytes doing mitosis and replicating themselves.  Mitosis is happening to the chondrocytes in the lacunae and new cartilage is being built in this zone.  But, the blue swath never really gets bigger.  It’s because the chondrocytes at the bottom of the blue swath are dying.  This white area here is the dying chondrocytes being calcified.

As this happens, osteoblasts are moving upward and replacing the newly formed and newly dead cartilage with bone.  I once heard someone say, “The osteoblasts chase the chondrocytes.” This pushes the epiphysis away from the diaphysis.  I like that because those chondrocytes are doing appositional growth only on this inferior edge.  Every time they replicate themselves, they push themselves more and more superior.  Then, the osteoblasts ossify the dead remains of the cartilage and follow the chondrocytes that are moving superiorly.


Closing the Epiphyseal Plate

The activity of the chondrocytes has ceased. The osteoblasts are no longer replacing the newly formed cartilage with bone tissue. As a result, the epiphyseal plate becomes an epiphyseal line.  This means that growth has ceased and there is no longer any activity to elongate the bone. 

Closing of the plate to a line is influenced by estrogen and testosterone in puberty, among other things.

You can see epiphyseal plates of long bones in x-rays.  When we talk about long bones, we tend to think of the femur and the humerus. However, the metacarpals, metatarsals, and all the phalanges are long bones too.  The open epiphyseal plate almost looks like an open space on an x-ray. It seems as though the epiphyses of the bone are not connected.  Once the plate closes, the epiphyseal line is made of all bone and there is no open space.  Thus, why we call them “open” plates to denote growth.


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