PATHOLOGY 8.1

• Osteoporosis


  Metabolic bone disorder where bone mineralisation density & microstructure are significantly below normal
• Osteopenia


  A pre-osteoporotic condition where bone mineralisation density is lower than normal, but not low enough to be regarded as osteoporosis
• Osteoblast


  Bone forming cell
• Osteoclast


  Bone resorbing cell
• Periosteum


  The layer that surrounds a bone
• Endosteum


  Incomplete cellular lining on the inner surface of bones
• Diaphysis


  The shaft of a long bone
• Metaphysis


  The region of a long bone between the epiphysis and diaphysis, corresponding to the location of epiphyseal cartilage
• Epiphysis


  The head of a long bone
• Trabecular bone


  Spongy bone, composed of a network of bony struts (porous bone)
• Compact bone


  Dense bone that contains parallel osteons
• Kyphosis


  Excessive outward curvature of the spine
• Bone remodelling process

  1. Osteoclasts undertake bone resorption
  2. Osteoclasts undergo apoptosis
  3. Osteocytes signal osteoblasts
  4. Osteoid formation
  5. Formation of hydroxyapatite
  6. Formation of quiescent bone
• Osteoblasts

  • Bone forming cell
  • Synthesis of organic matter
  • Location: edge of bone
• Osteoclasts

  • Bone resorbing cell
  • Releases lysosomal enzymes/acids that dissolve bone material
  • Location: edge of bone/in resorption pits
• Endocrine regulation of bone remodelling

  • Parathyroid hormone: stimulates bone resorption
  • Androgens: maintain bone density, inhibit bone resorption
  • Vitamin D: facilitates the deposition of calcium into the bone matrix
• RANKL


  Stimulates the production and activation of osteoclasts
• Osteoprotegerin (OPG)


  A decoy receptor that binds to RANKL, preventing it from interacting with RANK and inhibiting osteoclasts activation
• Sclerostin

  • Released by osteocytes
  • Decreases bone formation and increases bone resorption
• The RANKL:OPG Ratio

  • Osteoclast activation = bone resorption (OPG > RANKL)
  • Osteoclast inhibition = no bone resorption (RANKL > OPG)
• Bone strength is determined by bone quality and bone density
• Bone quality is determined by architecture, turnover, mineralisation and damage
• Characteristics of osteoporosis

  • Significant loss of bone mineral density
  • Loss of microstructure
  • Bones become brittle and fragile
  • Increased risk of fractures
• The underlying cause of osteoporosis is change in balance between formation and resorption of bone
• Classification of primary osteoporosis

  • Idiopathic: no known cause
  • Type 1: postmenopausal - oestrogen deficiency
  • Type 2: ageing
• Oestrogen is a promoter of bone growth
• Osteoporosis Pathogenesis

  • Imbalance in bone formation and resorption
  • Diameter increase, thinning of bone, loss of trabeculae
  • Less osteoclasts than osteoblasts
  • Affects diaphysis and metaphasis
• Osteoporosis Morphology

  • Trabecular bone initially affected --> then cortical bone
  • Decreased bone density
• Normal bone

  
• Osteoporosis

  
• Osteoporosis Clinical Manifestations

  • Asymptomatic
  • Fractures commonly in hip, wrist, pelvis, spine and ribs due to high proportion of trabecular bone
• Osteoporosis is diagnoses by measuring bone mineral density. This is achieved by a dual-emission x-ray absorption. A T score of -2.5 or less indicates osteoporosis
• Osteoporosis Management

  • Calcium and vitamin D supplementation
  • Anti-resorptive agents: Bisphosphates --> inhibit osteoclasts, reduce absorption of bone
  • Selective oestrogen receptor modulators (SERMs)
  • Strontium ranelate --> increase osteoblast proliferation and inhibits osteoclasts
• Osteomalacia


  Abnormal mineralisation of the osseous matrix and softening of the bones
• Rickets


  Characterized by the softening and weakening of bones in children and associated with poor mineralisation of the cartilage in the epiphyseal growth plate
• Rickets and osteomalacia are associated with a vitamin D deficiency
• In rickets and osteomalacia there is balance bone formation and reabsorption however the is defective mineralisation
• Changes in bone mineralisation

  Vitamin D deficiency results in reduced absorption of calcium, leading to hypocalcaemia. This condition causes an increase in phosphate excretion. In response, parathyroid hormone stimulates the release of calcium and phosphorus from bone stores to normalize blood calcium levels. However, the continuous release of calcium from bones leads to decreased bone mineralisation, resulting in bone softening, which is characteristic of conditions such as osteomalacia and rickets.
• Zones of the epiphyseal plate

  • Zone of resting cartilage: where chondrocytes differentiate
  • Zone of proliferation: where chondrocytes divide by mitosis
  • Zone of hypertrophy: where chondrocytes mature, enlarge and calcium is deposited into matrix
  • Zone of ossification: chondrocytes degenerate, calcify and bone forms, osteoblasts deposit osseous tissue
• In rickets disruption to calcium and vitamin D cause chondrocytes to fail, irregular and deformed expansion of cartilage tissue within growth plate