Bone Formation

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