2 types of Bone formation

1) Intramembranous Ossification
Development of ossification Center
Mesenchyme cells crowd together they will differentiate into
osteoprogenitor cells
Osteoprogenitor cells will then differentiate into osteoblasts
Osteoblasts will secrete matrix until they are surrounded by it
Calcification
Once osteoblasts are surrounded by extracellular matrix they then become
osteocytes
In a few days Calcium and other inorganic mineral salts will deposit in the
extracellular matrix
This will calcify the matrix
Formation of Trabeculae
As bone extracellular matrix forms it develops into trabeculae
The trabeculae fuse with one another around blood vessels and arteries
Development of Periosteum
Messechymal cells will condense together at the periphery of the bone to
form the periosteum
Eventually the periosteum will deposit compact bone around the outside
the bone
2) Endochondral Ossification
Development of Cartilage Model
Mesenchyme crowd together in general shape of bone they then
differentiate into chondroblasts
Chondroblasts secrete cartilage extracellular matrix, producing cartilage
model
Pericondrium develops around model
Growth of Cartilage Model
Model grows in 2 ways
Appositional Growth: Occurs in the perichondrium, the chondroblast
secrete more matrix and this cartilage model grows in width
Interstitially: chondroblasts experience mitosis in the center of the
cartilage model (this is how the model grows in length)
The cells within the model will then stop dividing and will begin to grow
in size (hypertrophy) due to the lack of nutrients getting to the cells
Some will grow so big that they will burst and spill their intracellular
contents into the matrix, this will change the pH or acidify the matrix
This acidity will draw Calcium to the matrix (which will calcify the
matrix)
Calcium is an inhibitor of diffusion and thus other cells around will go
through the same process of (hypertrophy, burst, die, acidify, calcify)
Development of Primary Ossification Center

The nutrient artery will then penetrate the perichondrium through the
nutrient foramen and will bring osteoprogenitor cells into the diaphysis
region as well it will bring blood
Once the artery has been brought in the osteoprogenitor cells will
differentiate into osteoblasts
The osteoblasts will then lay down bone extracellular matrix over the
remnants of calcified cartilage (forming spongy trabeculae)
Primary ossification spreads from center outwards
Development of Medullary Cavity
The nutrient artery will also bring in osteoclasts into the diaphysis along
with the osteoblasts
When compact bone is thick enough to support the mechanical stress
osteoclasts will absorb the trabecular bone on the inside of the diaphysis to
form the medullary cavity
Development of Secondary Ossification Center
This process is much like primary ossification
Chondrocytes will divide, grow, burst, die, acidify and the matrix will
calcify
The branches of the epiphyseal artery will enter the epiphysis bringing in
osteoprogenitor cells and blood as well as osteoclasts
Osteoblasts will turn cartilage model into bone tissue
In this case osteoclast will not absorb trabeculae (there will be no
medullary cavity
Development of Articular Cartilage
Not the entire epiphysis will be turned to bone
Around the edges will stay cartilage (this forms the articular cartilage)
As well in b/w the epiphysis and the diaphysis will stay cartilage (this is
the growth plate)
Growth in length
Bones grow in width through interstitial growth, this type of growth occurs within
a cartilage model
It happens when the chondrocytes undergo mitosis
In developed bones this type of growth cannot happen in the bone tissue
It occurs in the metaphysis region in the epiphyseal plate (this plate is made up of
hyaline cartilage)
The epiphyseal plate consists of 5 zones which aid to growth in length
The zone of resting cartilage: consists of small chondrocytes, this zone does not
actually aid in the growth process, but it does attach the epiphyseal plate to the
epiphysis
The zone of proliferating cartilage: Chondrocytes in this zone undergo rapid cell
division. This is the zone where interstitial growth occurs. The chondrocytes in
this zone look like stacks of coins.
The zone of hypertrophic cartilage: Chondrocytes in this zone stop dividing and
undergo growth in size. The chondrocytes are still arranged in stacks.

The zone of calcified cartilage: Chondrocytes are mainly dead here because the
extracellular matrix has calcified.
The zone of bone deposition: Osteoclasts dissolve the calcified cartilage, and
osteoblasts and capillaries from the diaphysis region invade the area. The
osteoblasts lay down bone extracellular matrix, replacing the calcified cartilage by
the process of endochondral ossification.

Growth in Width (appositional growth)

At bones surface the periosteal cells differentiate into osteoblasts
Secrete collagen fibers and other organic molecules that form bone extracellular
matrix
Once osteoblasts are surrounded by extracellular matrix they become osteocytes
This process forms bone ridges on either side of the periosteal blood vessel
The ridges slowly enlarge and create a groove for the blood vessel
The ridges will fold together and fuse, the groove becomes a tunnel that encloses
blood vessel
The former periosteum is now the endosteum and it lines the tunnel
Osteoblasts in the endosteum deposit bone extracellular matrix, forming new
concentric lamellae
This formation proceed inward, toward periosteal blood vessel
In this way the tunnel fills in and the new osteon is created
As osteon is forming, osteoblasts under the periostum deposit new circumferential
lamellae, further increasing the thickness of the bone.
As additional periosteal blood vessels become enclosed to form osteons the
growth process continues
**As bone is being deposited on the outside osteoclasts are absorbing bone tissue in the
medullary cavity, making the medullary cavity bigger while increasing the thickness**