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

Microscopic bone (Courtesy of RVC Histology images)

Cells

  • Osteoblasts, osteocytes, chondroblasts and chondrocytes are derived from stromal fibroblastic system (osteoprogenitor cells); osteoclasts from haematopoietic system
  • Ischaemia and hypoxia favour development of cartilage
  • High oxygen tension and good blood supply favour bone development
  • Osteoblasts
    • Mesenchymal cells
    • Arise from bone marrow stroma
    • Histologically:
      • Plump and cuboidal when active
      • Basophilic cytoplasm
      • When inactive - less cytoplasm -> flattened
    • Produce bone matrix = osteoid - uncalcified
      • Homogeneous substance
      • Stains light pink with H&E
    • Cell membranes are rich in alkaline phosphatase (ALP)
      • Possibly involved in pumping calcium across membranes
    • Promoted by growth factors
    • Have receptors for PTH
      • They contract in response -> space for osteoclasts to attach
  • Osteocytes
    • Osteoblasts that have become surrounded by mineralised bone matrix
    • Occupy cavities called lacunae
    • Contact osteoblasts and each other with cytoplasmic processes
      • Reach through canaliculi in mineralised bone matrix
    • Regulate composition of bone fluid
  • Osteoclasts
    • Histologically:
      • Large, often multinucleated cells
      • Acidophilic cytoplasm
    • Derived from haematopoietic stem cells
    • Responsible for bone resorption
      • Firstly dissolve mineral followed by collagen
      • Use brush border for this
    • Sit in bone surface depression - Howship's lacuna
    • Do not have receptors for PTH
    • Have receptors for calcitonin
      • Involute their brush border in response
      • Detach from bone surface
    • Respond to vitamin D by increasing their numbers and activity (parathyroid independent)


Matrix

  • Osteoid
    • Type I collagen forms the backbone of the matrix (90%)
      • Molecules in staggered rows
    • Non-collagenous protein forming amorphous ground substance (10%)
      • Mainly glycoproteins and proteoglycans
  • 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

  • Periosteum
    • Specialised sheath of connective tissue covering bone except at the articular surfaces
    • Loosely attached except at tendon insertions and boney prominences (associated with major blood vessels penetrating bone)
    • Histologically:
      • Outer layer - fibrous for support
      • Inner layer - osteogenic
        • Contains osteoblasts and osteoprogenitor stem cells in young animals and in adults with fractures or disease
    • Rich supply of nerves and lymph vessels
    • Damage to periosteum:
      • Invokes a hyperplastic reaction of the inner layer
      • Is painful
      • Exostoses can remodel or remain
    • Lifting of periosteum:
      • Causes new bone formation below
    • Circumferential incision (e.g. during fracture)
      • Longitudinal bone growth results
      • May be only on one side where periosteum is damaged
  • Blood vessels
    • Nutrient, metaphyseal, periosteal arteries
    • Normal flow of blood from medulla to periosteum due to higher pressures in medulla
    • Young animals have greater blood supply
  • 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)

Growth plate (Image sourced from Bristol Biomed Image Archive with permission)
Growth plate magnified(Image sourced from Bristol Biomed Image Archive with permission)


  • Originates from the cartilage model that remains only at the junction of the diaphyseal and epiphyseal centres


  • Cartilage of metaphyseal growth plate is divided into: (from right to left on the magnified image)
    • - Resting (reserve) zone
    • - Proliferative zone
    • - Hypertrophic zone



  • 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
    • Regulated by androgens
  • If growth teporarily stops -> layer of bone seals the growth plate -> moves into metaphysis when growth resumes -> forms Harris lines



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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