There are two processes of bone formation: intramembranous ossification and endochondral ossification. Intramembranous ossification occurs directly in mesenchymal tissue through osteoblast secretion and mineralization of bone matrix in flat bones and thickened portions of long bones. Endochondral ossification involves the development of long bones from a cartilage mold during embryogenesis, with primary ossification centers forming in the diaphysis and secondary centers later forming in the epiphyses, separated by the growth plate where chondrocytes proliferate and mature. Bone development is controlled systemically by hormones like growth hormone and thyroid hormone as well as locally by factors such as Indian hedgehog, PTHrP

1. BONE
DEVELOPMENT
S T U D E N T, D R . R K G M C H A M I R P U R

2. BONE FORMATION OCCURS IN TWO WAYS –
1. INTRAMEMBRANOUS OSSIFICATION
2. ENDOCHONDRAL OSSIFICATION
Intramembranous ossification –
occurs in membrane of mesenchyme
There is direct mineralization of matrix secreted by osteoblasts.
Occurs in –
1. Flat bones
2. Thickening of long bones
In mesenchymal membrane ,
group of mesenchymal cells
differentiate into osteoblasts
(primary center of ossification)
Osteoblasts form bone matrix
and calcification follows
Bone enlargement is achieved by
deposition of new bone on the
preexisting surface (appositional
growth)

3. ENDOCHONDRAL OSSIFICATION
Development of long bones from a cartilage mold during embryogenesis.
In secondary ossification centers , cartilage remains in two regions –
1. Articular cartilage
2. Epiphyseal plate of cartilage
Cartilage mold
(analgen)
• Formed from mesenchymal
precursor cells
• Central portion of analgen
is resorbed to form
medullary canal (8 weeks)
Ossification
centers
• Primary – at midshaft
(diaphysis) , formed from
osteoblasts adherence to calcified
matrix. Radial growth
• Secondary- at ends (epiphysis)
Centrifugal growth
Growth plate
formation
• Plate of cartilage Formed
between 2 expanding
centers of growth
• There is proliferation,
hypertrophy and apoptosis
of chondrocytes
Synthesis
capillaries of
osteoid
• In region of apoptosis, the
matrix mineralizes and is
invaded by capillaries
• capillaries nourishes
osteoblasts to form osteoid

4. .

5. FACTORS CONTROLLING BONE DEVELOPMENT
Systemic
Growth hormone
Thyroid hormone (T3)
PTH
Calcitonin
Local
• Indian hedgehog (Ihh) – coordinates chondrocyte proliferation and differentiation andosteoblasts
proliferation.
• Parathyroid hormone related protein (PTHrP) - activates the PTH
• receptor and maintains proliferation of chondrocytes.
Fibroblast growth factors (FGFs)
Bone morphogenic proteins (BMPs)
Proliferation and hypertrophy of chondrocytes