Bone formation occurs through two main processes: endochondral ossification and intramembranous ossification. Endochondral ossification involves the formation of long bones from cartilage templates. It is a multi-step process where cartilage is replaced by bone. First, primary ossification centers form in the diaphyses as bone collars prevent nutrient diffusion into cartilage, causing cartilage cell death. Blood vessels then invade and deposit osteoblasts that form trabecular bone. Secondary ossification centers later develop in the epiphyses through the same process. The epiphyseal plate contains proliferating and hypertrophying cartilage cells that drive bone growth until skeletal maturity is reached.

1. Bone Formation 101 Primary ossification centre
(bone formation inside area
So I noticed a bunch of you guys had some questions about bone formation – hope this answers most of your questions! enclosed by bone collar or
 NOTE: this is endochondral ossification we’re talking about  formation of bone from cartilage (hence “chondral” ending) region known as shaft
o This process is for the formation of long bones (diaphysis) of the bone.
 Flat bones are formed by intramembranous ossification.
PRIMARY OSSIFICATION CENTRE
1. Starting with piece of hyaline cartilage in shape of future bone, in the region of the
diaphysis (middle narrow part), perichondrium is transformed into periosteum
(black border)
a. Note: the whole piece of hyaline cartilage is surrounded by a perichondrium
except at the two ends that will become the articular surfaces
2. Periosteum deposits bone inside the cartilage forming bone collar
3. Bone collar prevents diffusion of nutrients, cartilage dies (hypertrophy & cell death),
EMC becomes calcified
4. Blood vessels from perichondrium/periosteum invades empty space left by
degenerating chondrocytes, carrying with them anything on bone surface inside.
 Stuff dragged in include: osteoprogenitor cells, osteoblasts
5. Osteoprogenitor cells differentiate into osteoblasts divide & secretes ECM Epiphyseal
 Completes formation of primary ossification centre plate is “fused”
– see how
there’s no
SECONDARY OSSIFICATION CENTRE
more cartilage!
1. Takes place at level of epiphysis of future bone
This bone can’t
2. Cartilage degenerates since it also gets choked off from nutrients by the bone collar get any longer.
(happens later than primary ossification centre – hence “secondary”)
3. Blood vessels again from the outside (perichondrium) also invade the space as the
cartilage deteriorates
4. The only cartilage left is at the articular surface and epiphyseal plate (all other
cartilage degenerates – remember it start off as a piece of hyaline cartilage!)
 Epiphyseal plate: layer of cartilage in between primary + secondary ossification
centre (cartilage persists until 20 years of age)
 Cartilage at the surface is classified as “articular” cartilage even though it began as
hyaline cartilage!
 Epiphyseal plate is still “hyaline” cartilage since the perichondrium is intact
 Metaphysis: area between epiphysis & diaphysis
Secondary ossification centre –
bone formation at the two ends
of the bone (epiphysis)

2. After that… (we’re at the stage of second last diagram above)
1. After the primary and secondary ossification centers have done their job – you end up a piece of bone formed from the chunk of hyaline cartilage
you started off with.
2. The long bone then lengthens via the action of the epiphyseal plate
3. As the chrondrogenic layer forms more hyaline cartilage, the epiphseal plate “grows” outwards (see [1] below)
4. However, the overall width of the plate does NOT increase because the other end is being chew up by osteoclasts (see [2]) – (so this is after the
chondrocytes go through the layers of hypertrophy, cell death, etc.)
Putting it in Perspective – what it really looks like Shaft (diaphysis)
becomes compact
[2] Big fat osteoCLASTS bone
[1] Direction of growth
chewing everything up
(due to cartilage
at this end
proliferation)
Mixed spicules (mixture
of cartilage & bone) –
osteoclasts chewing
away in this region.
Zoom in on the black box – epiphyseal plate
Skeletal muscle!
Cartilage at the head of
the bone remains – this is
the articular cartilage (no Head of bone (epiphysis) plate!)
perichondrium!) becomes filled with
spongy bone.

3. The Epiphyseal Plate
Zones in Epiphyseal Plate
1. Zone of resting cartilage
 Light pink, with chondrocytes trapped in lacuna, normal cartilage
2. Zone of proliferation
 Chondrocytes trapped in lacuna are proliferating  looks like stack of coins, very adidophillic
 Pushes resting layer up
3. Zone of hypertrophy
 Lacunas start to fill up with fluid  more space seen around chondrocytes, paler
4. Zone of cell death
 Chondrocytes start dying after death occurs in primary centre
 Nuclei disappears, cell ruptures
 Cells die due to hypertrophy above it  NOT because of bone collar (which doesn’t cover epiphysis)
5. Zone of mixed spicules (indistinct)
 Osteoblasts: got in via blood vesselsaround periphery of cartilage, lays down bone matrix (darker) over
calcified cartilage matrix (lighter)
 Osteoclasts: at the same time chew up newly synthesize bone + calcified cartilage
o Large, acidophilic, many nuclei
 Calcified cartilage: appears purple
 Zone of mixed spicules: mixed bone + calcified cartilage
o Pieces of bone formed when ECM engulfs osteocyte, consists of woven bone (immature), NOT
lamellar bone (compact bone of diaphysis)
NOTE: while bone is forming from cartilage and lengthening – the shape undergoes remodeling at the
same time  there’s a slide in your lectures that explain this pretty well. =)
Hope this clarifies things! You guys better get 100% on the short answer if bone formation appears. =)
Email me if you find anything ambiguous or discrepancies – this stuff is based on last year’s lectures so I don’t know if he introduced anything new.
heidi.wat@mail.mcgill.ca