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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