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Updated: Jun 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 accelerates 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
      • 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
      • cartilage model forms
        • mesenchymal cells differentiate into chondroblasts (cartilage cells) that form the hyaline cartilaginous skeletal precursor of the bones
      • 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. Marrow is simultaneously formed by resorption of central portion of the cartilage anlage by myeloid precursor cells that migrate in through the vascular buds.
      • cartilage model continues to grow
        • Cartilage and chondrocytes continue to grow at ends of the bone while medullary cavity expands and remodels.
      • 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)
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