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

• Cells
  • Osteoblasts
    • Mesenchymal cells
    • Arise from bone marrow stroma
    • Produce bone matrix = osteoid
    • Cell membranes are rich in alkaline phosphatase (ALP)
  • Osteocytes
    • Osteoblasts that have become surrounded by mineralised bone matrix
    • Occupy cavities called lacunae
  • Osteoclasts
    • Multinucleated cells
    • Derived from haematopoietic stem cells
    • Responsible for bone resorption (have a brush border for this)
• Matrix
  • Type I collagen forms the backbone of the matrix
  • Mineral – accounts for 65% of bone and includes Ca, P, Mg, Mn, Zn, Cu, Na

Bone organisation

• Patterns of collagen deposition:
  • Woven bone:
    • "Random weave" which is only a normal feature in the foetus
    • 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
    • Two main types:
      • Compact bone (cortical)
        • Forms 80% of total bone mass
        • Forms the shell of long bone shafts - contain Haversian systems
      • Cancellous bone (spongy or trabecular)
        • In vertebrae, flat bones and epiphyses of long bones
        • Contains no Haversian systems

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
• Damage to the periosteum invokes a hyperplastic reaction of the inner layer
• The blood supply to the mature bone enters via the periosteum

Bone development

• Two main types of bone development:
  • Endochondral ossification (cartilage model)
    • Long bones mainly
    • Vascularised
    • Developed centres of ossification
      • Primary (diaphyseal)
      • Secondary (epiphyseal)
  • Intramembranous ossification
    • Flat bones mainly (e.g. skull)
    • 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
  • Calcitonin
    • Produced by C-cells in the thyroid glands in response to increased serum calcium

    PTH

↓ Osteoclasts increase in number ↓ Osteoclasts attach to bone and resorb mineralised matrix

Osteoclasts do not have receptors for PTH so how do they do this? Answer:

LOW CALCIUM → INDUCES PTH SECRETION → BONE RESORPTION → CALCIUM 

CALCITONIN HAS THE OPPOSITE EFFECT - IT INHIBITS OSTEOCLASTS

Bone dynamics

Bone growth and maintenance of normal structure are directly related to mechanical forces which generate bioelectrical potentials (piezoelectricity). These potentials strengthen bone and inactivity reduces them, thereby leading to bone loss. In neonates, bone growth predominates and modelling is important. In adults, formation of bone is balanced by resorption; this is known as remodelling. It continues in a subtle but active way 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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