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
      • Used by surgeons to treat angular limb deformities
• 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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