Updated: 9/30/2020

Bone Formation

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Introduction
  • Bone formation (osteogenesis) can occur via two distinct processes that convert mesenchymal tissue to bone
    • endochondral ossification
      • mesenchymal tissue  cartilage intermediate  bone
    • intramembranous ossification
      • mesenchymal tissue  bone
  • Bone remodeling requires a  dynamic balance of formation and resorption that depends on multiple cell types
    • osteoblasts
    • osteocytes
    • osteoclasts
Endochondral Ossification
  • Overview
    • converts mesenchymal tissue to a cartilage intermediate and eventually to bone
    • occurs in several different osteogenic processes
      • embryonic long bone formation
      • longitudinal physis (growth plate) growth
      • non-rigid fracture healing
  • Steps
    • mesenchymal precursor cells commit to becoming cartilage cells (chondrocytes)
      • occurs via paracrine signaling
    • committed mesenchymal cells differentiate into chondrocytes
    • chondrocytes rapidly proliferate and secrete cartilage-specific extracellular matrix to form a cartilage model
    • chondrocytes die via apoptosis as the matrix calcifies
    • surrounding cells differentiate into osteoblasts to begin replacing degraded cartilage with bone matrix (osteoid)
    • blood vessels penetrate the diaphyseal cartilage core and osteoblasts form a primary ossification center
    • diaphyseal bone thickens and epiphyseal cartilage becomes calcified
    • blood vessels penetrate the epiphyseal cartilage core and osteoblasts form secondary ossification centers
      • initial bone is immature woven bone with irregular random collagen fibers
      • bone remodeling eventually converts immature woven bone to mature lamellar bone with parallel arranged collagen fibers
Intramembranous Ossification
  • Overview
    • converts mesenchymal tissue directly to bone
      • no cartilage intermediate
      • also known as Haversian remodeling
    • occurs in several different osteogenic processes
      • embryonic flat bone formation
        • skull
        • facial bones
        • clavicle
      • rigid fracture healing
  • Steps
    • mesenchymal cells proliferate and differentiate directly into osteoblasts
    • osteoblasts produce bone matrix (osteoid)
      • initial bone is immature woven bone with irregular random collagen fibers
      • bone remodeling eventually converts immature woven bone to mature lamellar bone with parallel arranged collagen fibers
Bone Remodeling
  • Multiple cell types are required for healthy bone remodeling
    • osteoblasts
      • function
        • bone-forming cells
          • produce a collagen-proteoglycan matrix that can bind calcium salts for osteoid calcification
      • origin
        • derived from fibroblasts
    • osteocytes 
      • function
        • bone cells
          • transmit signals through bone
          • secrete growth factors to regulate activity of osteoblasts and osteoclasts 
      • origin
        • derived from osteoblasts that become embedded in bone matrix
    • osteoclasts 
      • function
        • bone-resorbing cells
          • mobilize matrix minerals via acidification, then degrade matrix material via proteases
      • origin
        • derived from monocytes
  • clinical relevance
    • involved in correction of displacement and angulation in pediatric fractures 
      • requires the coordinated activity of
        • osteoclasts in reabsorbing the convex side of the deformity
        • osteoblasts in filling the concave side of the deformity
    • inadequate osteoblastic activity will lead to impaired bone mineralization
      • rickets/osteomalacia
    • excess osteoclastic activity will lead to increased bone resorption
      • osteoporosis
      • Paget disease of bone
      • osteitis fibrosa cystica
    • inadequate osteoclastic activity will lead to insufficient bone resorption
      • osteopetrosis
 

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