Updated: 6/18/2021

Endochondral Bone Formation

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  • Introduction
    • Endochondral bone formation occurs in
      • longitudinal physeal growth
      • embryonic long bone formation
      • non-rigid fracture healing (secondary healing)
    • Cell biology
      • endochondral 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 endochondral 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
    • Longitudinal physeal growth
      Reserve zone (B) 
      • Cells store lipids, glycogen, and proteoglycan aggregates for later growth and matrix production
      • Low oxygen tension
      • Gaucher's
      • Diastrophic dysplasia
      • Kneist
      • Pseudoachondroplasia
      Proliferative zone (C)
      • 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 (D)
      • 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 zonefurther 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, expression regulated by Indian hedgehog gene)
      • Type X collagen produced by hypertrophic chondrocytes important for mineralization
      • SCFE (not renal)
      • Rickets (provisional calcification zone)
      • Enchondromas
      • Mucopolysacharide disease
      • Schmids
      • Fractures most commonly occur through zone of provisional calcification
      Primary spongiosa (E)
      (metaphysis)
       
      • Vascular invasion and resorption 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 the 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
      Perichondrial artery
      • Major source of nutrition to physis
  • 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 endochondral 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)
      • 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)
    • 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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(OBQ12.123) Which of the following would lead to accelerated maturation in the zone of hypertrophy at the physis?

QID: 4483
1

An activating mutation in TGF-ß

25%

(1006/4024)

2

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

32%

(1276/4024)

3

A deactivating mutation in prostaglandin E2

5%

(207/4024)

4

An activating mutation in the SMAD-3 protein

15%

(594/4024)

5

An activating mutation in the Indian Hedgehog (Ihh) protein

22%

(867/4024)

L 5 B

Select Answer to see Preferred Response

(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?

QID: 3234
FIGURES:
1

Longitudinal bone growth

15%

(429/2895)

2

Appositional bone growth

61%

(1753/2895)

3

Supplying cartilage cells to the articular surface

7%

(200/2895)

4

Calcification of the matrix within the growth plate

7%

(207/2895)

5

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

10%

(289/2895)

L 3 B

Select Answer to see Preferred Response

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

QID: 3028
1

No effect

1%

(24/1604)

2

Accelerated longitudinal growth

8%

(122/1604)

3

Decelerated longitudinal growth

88%

(1407/1604)

4

Decelerated apposition growth

2%

(37/1604)

5

Decreased bending strength of the bone

0%

(7/1604)

L 1 C

Select Answer to see Preferred Response

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

QID: 852
FIGURES:
1

A

2%

(19/1201)

2

B

13%

(162/1201)

3

C

53%

(631/1201)

4

D

28%

(339/1201)

5

E

4%

(46/1201)

L 3 B

Select Answer to see Preferred Response

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

QID: 862
1

resting zone

9%

(83/888)

2

proliferative zone

24%

(211/888)

3

zone of hypertrophy

62%

(548/888)

4

metaphysis

4%

(34/888)

5

diaphysis

1%

(7/888)

L 3 B

Select Answer to see Preferred Response

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

QID: 774
FIGURES:
1

Resting zone

1%

(11/1935)

2

Proliferative zone

32%

(625/1935)

3

Zone of maturation

8%

(164/1935)

4

Zone of degeneration

3%

(62/1935)

5

Zone of provisional calcification

55%

(1065/1935)

L 3 B

Select Answer to see Preferred Response

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

QID: 145
1

Resting zone

3%

(28/1006)

2

Proliferative zone

36%

(360/1006)

3

Zone of maturation

10%

(99/1006)

4

Zone of degeneration

2%

(17/1006)

5

Zone of provisional calcification

49%

(497/1006)

L 3 B

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