Endochondral ossification replaces cartilage with bone, while intramembranous ossification does not require a cartilaginous template.

Because compact bone provides strength and support for the body, it needs to be made of materials that are hard and can withstand large amounts of stress. The bone matrix is made up of organic and inorganic components. The organic components of bone include collagen and an unmineralized structure called osteoid. However, bone also has several inorganic components that help to make it hard. The primary inorganic component of bone, called hydroxyapatite, that makes bone hard is a mineral salt made mostly of calcium phosphate. This salt appears as a very condensed, needlelike crystal found in the matrix of the bone. These crystals do not decay rapidly, which is why bones containing them last for millions of years after death. Scientists have been able to isolate the crystals from fossils to determine how the bones of ancient organisms are organized.

Ossification is the process of bone tissue formation. This involves two different processes. The first, called endochondral ossification, results in the replacement of cartilage with bone. This occurs during development in humans, before birth. In the early stages of development, the skeleton is composed mostly of cartilage. Endochondral ossification needs the cartilage to be present before it can proceed because the cartilage is broken down as the bone forms. At around eight weeks, this cartilage skeleton starts to be replaced with bone through a series of steps.

Step 1, Degenerating cartilage: Chondrocytes, or cartilage-producing cells, enlarge in the central diaphysis shaft. The cartilage matrix starts to deteriorate, and a periosteal bone collar begins to form around the diaphysis. This becomes the primary site of ossification. The cartilage also continues to grow in some areas of the forming bone, which increases its length.

Step 2, Primary ossification center: Nutrient arteries and veins enter the central shaft. Fibroblasts, or connective tissue-forming cells, migrate into the area and develop into osteoblasts, which soon start to deposit calcium phosphate into the degrading cartilage. Bone-covered cartilage trabeculae, a precursor to spongy bone, begin to form. Spongy bone formation continues to spread to both ends of the shaft.

Step 3, Secondary ossification center: Osteoclasts break down the spongy bone, which forms the medullary cavity in the center of the diaphysis. At this time, the epiphyses are made entirely of cartilage that has moved along the shaft of the bone toward the ends. The cartilage moves as the diaphysis cartilage is ossified. A secondary site of ossification forms at one or both epiphyses. This secondary site will aid in the conversion of cartilage to bone in these areas.

Step 4, Bone replaces cartilage: Just like in the diaphysis, cartilage in the epiphyses is replaced with bone minerals. However, during this secondary form of ossification, no medullary cavity is formed, nor is the spongy bone destroyed. Instead, the spongy bone is kept within the epiphysis.

Step 5, Mature bone: Ossification of the epiphyseal plates occurs, forming epiphyseal lines.

The Process of Endochondral Ossification

During endochondral ossification, bone forms through the gradual replacement of cartilage. This is due to the work of osteoblast and osteoclast cells at the primary and secondary ossification sites.

The other form of ossification is called intramembranous ossification. During intramembranous ossification, bones are formed, but without the precursor cartilage being present. The bones of the skull and clavicle are formed in this manner. Similar to endochondral ossification, intramembranous ossification starts with the formation of an ossification center. This initiates the formation of osteoblasts. Osteoid is produced and then hardens around some of the osteoblasts. These trapped osteoblasts become osteocytes. The osteoblasts form simple spongy bone and the periosteum. The final step involves the replacement of spongy bone with compact bone and the formation of red bone marrow.


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