Bone Response to Damage

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Introduction

  • Bone is a hard, highly specialised connective tissue
  • Consists of interconnected cells embedded in a calcified, collagenous matrix
  • Living, dynamic, responsive tissue, growing and remodelling throughout life
  • Pathogenesis of many bone diseases is complex
    • May involve genetic defects, diet or infection or a combination of these
  • Function:
    • Support/protection
    • Movement
    • Stem cell storage
    • Mineral storage


Normal structure

Osteoclast - large cell in bottom right quadrant (Courtesy of RVC Histology images)
  • Cells
    • Osteoblasts
      • Mesenchymal cells
      • Arise from bone marrow stroma
      • Produce bone matrix = osteoid - uncalcified
      • Cell membranes are rich in alkaline phosphatase (ALP)
      • Promoted by growth factors
      • Plump, cuboidal basophilic cells
    • Osteocytes
      • Osteoblasts that have become surrounded by mineralised bone matrix
      • Occupy cavities called lacunae
    • Osteoclasts
      • Large, often multinucleated cells
      • Acidophilic cytoplasm
      • Derived from haematopoietic stem cells
      • Responsible for bone resorption (have a brush border for this)
      • Sit in bone surface depression - Howship's lacuna
  • Matrix:
    • Osteoid
      • Type I collagen forms the backbone of the matrix (90%)
      • Non-collagenous protein forming amorphous ground substance (10%)
    • Mineral
      • Crystalline lattice of calcium phosphate and calcium carbonate
      • Also contains Mg, Mn, Zn, Cu, Na, F
      • Accounts for 65% of bone


Bone organisation

  • Patterns of collagen deposition:
    • Woven bone:
      • "Random weave" which is only a normal feature in the foetus
      • Coarse collagen fibres
      • Later removed by osteoclasts and replaced by lamellar bone
      • In adults it is a sign of a pathological condition (e.g. fracture, inflammation, neoplasia)
    • Lamellar bone:
      • Orderly layers which are much stronger than woven bone
      • Fine collagen fibres in concentric or parallel laminae
      • Two main types:
        • Compact bone (cortical)
          • Forms 80% of total bone mass
          • Consists of cells and interstitial substance - 30% ossein (type of collagen) and 70% minerals, especially calcium phosphate
          • Forms the shell of long bone shafts - contain Haversian systems
        • Cancellous bone (spongy or trabecular)
          • Made up of plates, tubes or bars arranged in lines of stress
          • In vertebrae, flat bones and epiphyses of long bones
          • Contains no Haversian systems
    • Laminar bone
      • Formed on periosteal surface of diaphysis
      • Accomodates rapid growth of large dogs and farm animals
      • Plates of woven bone from within the periosteum
      • Concentric plates
      • As it forms, it fuses with the bone surface


Periosteum and blood supply

  • Specialised sheath of connective tissue covering bone except at the articular surfaces
  • Inner layer
    • Merges with the outer layer of bone
    • Contains osteoblasts and osteoprogenitor stem cells in young animals and in adults with fractures or disease
  • Damage to the periosteum invokes a hyperplastic reaction of the inner layer
  • The blood supply to the mature bone enters via the periosteum
  • Endosteum lines the marrow cavity


Bone development

  • Two main types of bone development:
    • Endochondral ossification (cartilage model)
      • Long bones mainly - physis and metaphysis
      • Mesenchymal cells differentiate into chondroblasts
        • Produce scaffold of mineralised cartilage on which osteoblasts deposit bone
      • Vascularised
      • Developed centres of ossification
        • Primary (diaphyseal)
        • Secondary (epiphyseal)
    • Intramembranous ossification
      • Flat bones mainly (e.g. skull), shaft of long bones
      • Mesenchymal cells differentiate into osteoblasts
      • No cartilage precursor template


Physis (Growth plate)

  • Originates from the cartilage model that remains only at the junction of the diaphyseal and epiphyseal centres
  • Site of many congenital or nutritional bone diseases in the growing animal
  • Open in neonates and growing animals
    • Chondrocyte proliferation balances cell maturation and death
  • Closes and ossifies at maturity


Bone resorption

  • Mediated by two hormones:
    • Parathyroid hormone (PTH)
      • Produced by chief cells in the parathyroid glands in response to decreased serum calcium
      • In response, osteoclasts increase in number and resorb mineralised matrix - increase Ca in blood
    • Calcitonin
      • Produced by C-cells in the thyroid glands in response to increased serum calcium
      • Inhibits osteoclasts


Bone dynamics

  • Bone growth and maintenance of normal structure are directly related to mechanical forces
  • Mechanical forces generate bioelectrical potentials (piezoelectricity)
    • These potentials strengthen bone
    • Inactivity reduces the potentials -> bone loss
  • In neonates:
    • Bone growth predominates
    • Modelling is important
  • In adults:
    • Formation of bone is balanced by resorption - remodelling
    • Continues throughout life under the influence of hormones and mechanical pressure
    • Bone resorption may exceed formation in pathological states (hormonal, trauma, nutritional) or in old age and disuse


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