Updated: 5/13/2019

Endochondral Bone Formation

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Introduction
  • Enchondral bone formation occurs in
    • longitudinal physeal growth
    • embryonic long bone formation
    • non-rigid fracture healing (secondary healing)
  • Cell biology
    • enchondral bone formation occurs with a cartilage model
      • chondrocytes produce cartilage which is absorbed by osteoclasts
      • osteoblasts lay down bone on cartilaginous framework (bone replaces cartilage, cartilage is not converted to bone)
      • forms primary trabecular bone
      • bone deposition occurs on metaphyseal side 
      • type X collagen associated with enchondral ossification
  • Molecular biology
    • chondrocytes play a critical role in endochondral bone formation throughout the formation of the cartilage intermediate
    • transcription factors involved in regulation of chondrocytes include 
      • Sox-9 
        • considered a major regulator of chondrogenesis, regulates several cartilage-specific genes during endochondral ossification, including collagen types II, IV, and XI and aggrecan
      • PTHrP
        • delays differentiation of chondrocytes in the zone of hypertrophy
  • Biomechanics
    • variables that affect growth across the physis
      • Hueter-Volkmann Law
        • compression across the growth plate slows longitudinal growth 
        • tension accerelates longitudinal growth
Anatomy
  • Blood supply
    • perichondrial artery  
      • You have not been heard from for a while.
         major source of nutrition to physis
Longitudinal Physeal Growth
 
Physeal Growth Plate
(letters on left correspond to histology in top right)
Reserve Zone  
  • Cells store lipids, glycogen, and proteoglycan aggregates for later growth and matrix production
  • Low oxygen tension


  • Gaucher's
  • diastrophic dysplasia
  • Kneist*
  • Pseudoachondroplasia*
Proliferative Zone  
  • Proliferation of chondrocytes with longitudinal growth and stacking of chondrocytes.
  • Highest rate of extracellular matrix production
  • Increased oxygen tension in surroundings inhibits calcification


  • Achondroplasia
  • Gigantism
  • MHE
Hypertrophic Zone  
  • Zone of chondrocyte maturation, chondrocyte hypertrophy, and chondrocyte calcification.
  • Three phases occur in the hypertrophic zone
    • Maturation zone: preparation of matrix for calcification, chondrocyte growth
    • Degenerative zone: further preparation of matrix for calcification, further chondrocyte growth in size (5x)
    • Provisional calcification zone: chondrocyte death allows calcium release, allowing calcification of matrix
  • Chondrocyte maturation regulated by local growth factors (parathyroid related peptides, expession regulated by Indian hedgehog gene)
  • Type X collagen produced by hypertrophic chondrocytes important for mineralization
  • SCFE (not renal)
  • Rickets (provisional calcification zone)
  • Enchondromas
  • Mucopolysarcharide disease
  • acromegaly
  • SED
  • MED
  • Schmids
  • Kneist*
  • Pseudoachondroplasia*
  • Fractures most commonly occur through the zone of provisional calcification, specifically Salter-Harris I fractures
Primary Spongiosa
(metaphysis) 
 
  • Vascular invasion and resportion of transverse septa.
  • Osteoblasts align on cartilage bars produced by physeal expansion.
  • Primary spongiosa mineralized to form woven bone and then remodels to become secondary spongiosa (below)
  • Metaphyseal "corner fracture" in child abuse
  • Scurvy
Secondary spongiosa
(metaphysis)
  • Internal remodeling (removal of cartilage bars, replacement of fiber bone with lamellar bone)
  • External remodeling (funnelization)
  • Renal SCFE
Physis Periphery
Groove of Ranvier
  • During the first year of life, the zone spreads over the adjacent metaphysis to form a fibrous circumferential ring bridging from the epiphysis to the diaphysis.
  • This ring increases the mechanical strength of the physis and is responsible for appositional bone growths
    • supplies chondrocytes to periphery

 

  • Osteochondroma

Perichondrial fibrous ring of La Croix

  • Dense fibrous tissue that is the primary limiting membrane that anchors and supports the physis through peripheral stability

 
Embryonic Long Bone Formation
  • Overview
    • allows growth in width and length
    • formed from mesenchymal anlage around 6th week in utero.
  • Steps of formation include
    • vascularization
      • vascular buds invade the mesenchymal model
    • primary ossification centers form
      • (at ~ 8 weeks) osteoprogenitor cells migrate through vascular buds and differentiate into osteoblasts forming the primary ossification centers
    • cartilage model forms
      • grows through appositional (width) and interstitial (length) growth
    • marrow forms
      • marrow is formed by resorption of central portion of the cartilage anlage by myeloid precursor cells that migrate in through the vascular buds
    • secondary ossification centers form
      • develop at bone ends and lead to epiphyseal ossification center (growth plate)
Non-Rigid Fracture Healing
  • Overview
    • mechanism of bone formation is similar to physeal enchondral ossification
  • Cell biology
    • soft callus is the cartilage intermediate
    • bone replaces callus via same chondrocyte proliferation, chondrocyte hypertrophy, and finally chondrocyte calcification
  • Examples include
    • casting and bracing
    • intramedullary nailing
      • allows for motion at the fracture site, which promotes bone formation both directly (intramembranous ossification) and through a cartilage intermediate (endochondral ossification)
 

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Questions (8)
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(OBQ12.123) Which of the following would lead to accelerated maturation in the zone of hypertrophy at the physis? Review Topic

QID: 4483
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1

An activating mutation in TGF-ß

25%

(915/3696)

2

A deactivating mutation in the parathyroid hormone-related peptide (PTHrP) receptor

32%

(1183/3696)

3

A deactivating mutation in prostaglandin E2

5%

(197/3696)

4

An activating mutation in the SMAD-3 protein

15%

(544/3696)

5

An activating mutation in the Indian Hedgehog (Ihh) protein

21%

(784/3696)

L 5

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(OBQ10.146) A 10-year-old male presents to the emergency department after his left ankle came into contact with the rotating blades of a lawn mower. He has a deep open laceration over his medial malleolus, and a radiograph is shown in Figure A. There is concern for a peripheral growth plate injury in the region of the groove of Ranvier. What is this region of the growth plate responsible for? Review Topic

QID: 3234
FIGURES:
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1

Longitudinal bone growth

15%

(375/2558)

2

Appositional bone growth

61%

(1552/2558)

3

Supplying cartilage cells to the articular surface

7%

(169/2558)

4

Calcification of the matrix within the growth plate

7%

(190/2558)

5

Organization of the growth plate into distinct zones of proliferation and hypertrophy.

10%

(256/2558)

L 3

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(OBQ09.215) Sustained compression applied to a growth plate under experimental conditions has what effect? Review Topic

QID: 3028
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1

No effect

1%

(15/1240)

2

Accelerated longitudinal growth

8%

(95/1240)

3

Decelerated longitudinal growth

88%

(1091/1240)

4

Decelerated apposition growth

2%

(28/1240)

5

Decreased bending strength of the bone

0%

(5/1240)

L 1

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(OBQ07.191) Gigantism affects which region of the growth plate labeled in Figure A? Review Topic

QID: 852
FIGURES:
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1

A

1%

(10/816)

2

B

12%

(101/816)

3

C

53%

(434/816)

4

D

29%

(238/816)

5

E

4%

(30/816)

L 3

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(OBQ07.201) What region of the physis does collagen type X play a prominent role? Review Topic

QID: 862
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1

resting zone

10%

(54/551)

2

proliferative zone

25%

(138/551)

3

zone of hypertrophy

61%

(335/551)

4

metaphysis

3%

(17/551)

5

diaphysis

1%

(3/551)

L 3

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(OBQ07.113) The fracture seen in Figures A and B is most likely to occur in which of the following growth plate zones? Review Topic

QID: 774
FIGURES:
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1

Resting zone

1%

(9/1718)

2

Proliferative zone

32%

(554/1718)

3

Zone of maturation

8%

(146/1718)

4

Zone of degeneration

3%

(50/1718)

5

Zone of provisional calcification

55%

(951/1718)

L 3

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(OBQ06.34) Salter-Harris type I fractures typically occur through which zone of the physis? Review Topic

QID: 145
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1

Resting zone

3%

(24/737)

2

Proliferative zone

40%

(294/737)

3

Zone of maturation

12%

(86/737)

4

Zone of degeneration

2%

(15/737)

5

Zone of provisional calcification

42%

(313/737)

L 3

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