Bone Formation & Development

Bone Formation is a normal process that leads to longitudinal and breadth growing of the bone. It’s called bone ossification or osteogenesis.

Anatomy of Physeal Growth Plate

There are two growth plates in immature long bones: horizontal (the physis) and spherical (growth of the epiphysis), the spherical plate is less organized than the horizontal plate.

The perichondrial artery is the major source of nutrition of growth plate.

See Also: Bone Cells

Physeal Cartilage Zones

There are 3 main physeal cartilage zones in the growth plate:

Reserve zone

Cells of Reserve zone store lipids, glycogen, and proteoglycan aggregates. The oxygen tension is decreased in this zone.

Pathologies occur in reserve zone are:

1. Gaucher’s disease.
2. diastrophic dysplasia.
3. Kneist.
4. Pseudoachondroplasia.

Proliferative zone

Longitudinal growth occurs in this zone with stacking of chondrocytes (the top cell is the dividing “mother” cell). Growth hormone exerts its effect in the proliferative zone. Cellular proliferation, and matrix production also occurs here.

The increased oxygen tension and proteoglycans inhibit calcification in this zone.

Pathologies occur in proliferative zone are:

1. Achondroplasia
2. Gigantism
3. Multiple hereditary exostosis (MHE).

Hypertrophic zone

The chondrocyte maturation, hypertrophy and calcification occurs in this zone. It’s characteristics by low oxygen tension and decreased proteoglycan aggregates.

Hypertrophic zone divided into three zones:

1. Maturation Zone: preparation of matrix for calcification, chondrocyte growth
2. Degeneration Zone: further preparation of matrix for calcification, further chondrocyte growth in size (5x)
3. Provisional calcification Zone: chondrocyte death allows calcium release, allowing calcification of matrix.

Pathologies occur in hypertrophic zone are:

1. Slipped capital femoral epiphysis SCFE.
2. Rickets (provisional calcification zone).
3. Enchondromas.
4. Mucopolysarcharide disease.
5. Acromegaly.
6. Multiple epiphyseal dysplasia (MED)
7. Schmids disease.
8. Kneist disease.
9. Pseudoachondroplasia.
10. Fractures most commonly occur through the zone of provisional calcification, specifically Salter-Harris I fractures.

See Also: Bone Types

Metaphysis

Metaphysis is adjacent to the physis and expands with skeletal growth.

Metaphysis has two regions:

• Primary spongiosa:
  • Its main functions are vascular invasion and resorption of transverse septa and bone formation.
  • Osteoblasts align on cartilage bars produced by physeal expansion.
  • It mineralized to form woven bone and then remodels to become secondary spongiosa.
  • The disease in this zone include: Metaphyseal chondrodysplasia (Jansen and Schmid types) and acute hematogenous. osteomyelitis
• Secondary spongiosa:
  • Its main functions are internal remodeling (removal of cartilage bars, replacement of fiber bone with lamellar bone) and external remodeling (funnelization).
  • The disease in this zone include: Osteopetrosis, Osteogenesis imperfecta, Scurvy and Metaphyseal dysplasia (Pyle disease).

Periphery of the physis

• Groove of Ranvier: supplies chondrocytes to the periphery for lateral growth (width).
• Perichondrial ring of La Croix: dense fibrous tissue, primary membrane anchoring the periphery of the physis.

Types of bone formation

The types of bone formation are Enchondral, Intramembranous Bone Formation and Appositional ossification.

Enchondral Bone Formation

Undifferentiated cells secrete cartilaginous matrix and differentiate into chondrocytes. The matrix mineralizes and is invaded by vascular buds that bring osteoprogenitor cells. The osteoclasts resorb calcified cartilage and osteoblasts form bone. Bone replaces the cartilage model, the cartilage is not converted to bone.

Enchondral bone formation occurs in:

1. Embryonic formation of long bones.
2. Longitudinal growth (physis).
3. Fracture callus (Non-rigid fracture healing (secondary healing).
4. Bone formed with demineralized bone matrix.

See Also: Factors affecting Fracture Healing

Embryonic formation of long bones

• Vascular buds invade the mesenchymal model, bringing osteoprogenitor cells that differentiate into osteoblasts and form the primary ossification centers at 8 weeks.
• Differentiation of osteoprogenitor cells is stimulated by binding of WNT protein to the LRP5 or LRP6 receptor.
• Cartilage model increases in size through appositional (width) and interstitial (length) growth.
• Marrow forms by resorption of the central cartilage anlage by invasion of myeloid precursor cells that are brought in by capillary buds.
• Secondary ossification centers develop at bone ends, forming the epiphyseal centers (growth plates) responsible for longitudinal growth.
• Arterial supply is rich during development, with an epiphyseal artery (terminates in the proliferative zone), metaphyseal arteries, nutrient arteries, and perichondrial arteries.

Intramembranous Bone Formation

Intramembranous Bone Formation Occurs without a cartilage model. Undifferentiated mesenchymal cells aggregate into layers (or membranes), differentiate into osteoblasts, and deposit an organic matrix that mineralizes.

Intramembranous Bone Formation occurs in:

1. Embryonic flat bone formation.
2. Bone formation during distraction osteogenesis.
3. Blastema bone (in young children with amputations).

Appositional ossification

• Osteoblasts align on the existing bone surface and lay down new bone
• Examples of appositional ossification include:
  1. Periosteal bone enlargement (width).
  2. The phase of bone remodeling.

References & More

1. Millers Review of Orthopaedics -7th Edition Book.
2. Campbel’s Operative Orthopaedics 12th edition Book.
3. El Sayed SA, Nezwek TA, Varacallo M. Physiology, Bone. [Updated 2022 Oct 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441968/