4/17 Paget Disease of Bone - Corbett

Question 1

Paget disease of bone

Answer 1

focal disorder of bone metabolism (occurs w aging)

• primary cellular disorder: incr osteoclastic bone resorption
  
  • incr bone turnover → accelerated remodeling → bone overgrowth
    
    • osteoarthritis
    • nerve impingement
    • incr risk of osteosarcoma
• impaired bone integrity

sites: skull, pelvis, spine, long bones

Question 2

pathophysiology: Pagets disease

Answer 2

osteoclast physio is altered:

• hypersensitive to vit D (1,25 OH2 D3) and RANK-L

osteoclast phenotype altered:

• too many nucleoli (normal: 3-20. Paget: 100)
• intranuclear inclusion bodies present

if you suppress osteoclast activity…bone remodeling is restored to normal levels

• tx: bisphosphonates

Question 3

risk

genetic, environmental

Answer 3

genetic:

• family hx
• Western European
• SQSTM1 truncation mutations → incr risk (not disease causing)
  
  • adaptor protein that facilitates protein transport to proteosome
  • modulates NFkappaB signalling

environment:

• paramyxovirus? maybe…see Paget-like changes, but no direct evidence

Question 4

Pagetic bone

Answer 4

• large osteoclasts
• thickened trabeculae : bone rimmed with osteoblasts, marrow replaced by stromal cells
• extremely vascular

Question 5

stages of Paget disease

Answer 5

1. osteolytic stage
   * clast activity predominates
2. mixed stage

• blast activity
• lots of “woven bone” with high volume and lousy structural integrity

3. osteosclerotic state
   * “burned out’

Question 6

histology comparison

xray of bone

Answer 6

Question 7

physical findings

Answer 7

• skeletal expansion → “frontal bossing”
• distortion → bowing of femur/tibia
• hypervascularity → palpably warm bone

Question 8

how discover?

(“accidental discovery”)

Answer 8

• elevated serum alk phos
  
  • reflects number of osteoblasts in sclerotic lesions, rate of bone formation
    
    • level of activity correlates directly with extent of skeletal involvement and how “active”
• sometimes discovered on radiographic imaging
• bone scintigraphy
  
  • technetium-99-DP uptake depends on blood flow and rate of new bone formation

Question 9

treatment

Answer 9

• aminobisphosphonate (ex. risedronate): aims to normalize alk phos