Week 3. Paget's Disease

Question 1

List the two forms of Paget’s disease and briefly compare the incidence and sites affected by the two forms.

Answer 1

• Monostotic (15%) – Tibia, femur, skull, vertebrae, humerus
• Polyostotic (85%) – Tibia, femur, skull, vertebrae (70%), humerus, pelvis (65%), sacrum (same as monostotic plus pelvis and sacrum)

Question 2

Briefly describe the events occurring in each of the three stages of Paget’s disease of bone

Answer 2

1. Osteolytic phase
   a. Normal bone resorbed by uncoupled activity from abnormal osteoclasts (more numerous, larger and more nuclei than normal)
   b. Bone turnover increases up to 20x normal (net bone loss)
   c. Results in “flame” lesions on radiograph
2. Mixed osteolytic-osteoblastic
   a. Uncoupled and excessive bone destruction (osteoclasts) and woven bone formation (osteoblasts)
   b. Woven bone replaces normal bone due to lag in mineralization
   c. Bone volume remains approximately normal
   d. Bone becomes highly vascularised
   e. Bone laid down in haphazard manner and persistence in osteoid seams results in “mosaic pattern” in bone (pathognomonic of Paget’s disease)
3. Osteosclerotic phase
   a. Decrease in osteoclastic activity with continued woven bone formation (osteoblasts) leads to increased density (“sclerosis”)
   b. Eventually, osteoblastic activity also decreases and condition becomes quiescent
   c. Aka “burn-out” phase – minimal/absent bone resorption and formation
   d. Radiologically see macroscopic features – Anterior bowing, sagging of femoral neck, enlarged and deformed skull, coarsened facial bones, vertebral weakening and collapse (increased kyphosis)

Question 3

Discuss the typical macroscopic features of pagetic bone

Answer 3

Macroscopic – seen in osteoscleotic phase

• Anterior bowing (femur, tibia)
• Sagging on femoral neck
• Enlarged, deformed skull
• Coarsened facial bones
• Vertebral weakening and collapse (increased kyphosis)

Question 4

Discuss the typical microscopic features of pagetic bone

Answer 4

Microscopic

• Howship lacuma indicates active bone resorption
• Large, multinucleated osteoclasts
• Fibrovascularisation
• “Cement lines” (mosaic pattern) – New bone laid down in haphazard manner
• Absence of regular lamellae

Question 5

Discuss the clinical manifestations of Paget’s disease

Answer 5

• Asymptomatic – Usually monostotic form
• Bone pain – Most common Sx, commonly polyostotic form
• Warmth over affected bones – Due to increased vascularity
• Sponginess of bone on palpation – Due to bone being soft and porous
• Deformity – Anterior bowing (femur, tibia), enlarged/thickened skull, kyphosis (collapse of vertebrae), leontiasis ossea of facial bones
• Neuro Ssx – Expanding bones place pressure on nerves, brain or spinal cord  HA, hearing loss and tinnitus, visual disturbance, various neuropathies
• Ischaemia – Pressure from expanding bone on blood vessels

Question 6

Discuss the radiological diagnosis of Paget’s disease

Answer 6

Radiographic findings

• Patchy radiolucent lesions (osteolytic phase) – Due to abnormal/excessive osteoclastic activity
• “Flame lesions” (osteolytic phase)
• Irregular sclerosis (sclerotic phase) – Due to increased osteoblastic activity
• Cortical thickening and bowing (sclerotic phase) – Increased woven (weak) bone production, inability to handle load
• “Cotton wool” appearance of cranial bones – Due to patchy sclerosis (sclerotic phase)

Question 7

6. Discuss the laboratory diagnosis of Paget’s disease

Answer 7

Lab investigations
Biochemical findings
-	Indices of bone resorption
o	Urinary hydroxyproline
o	Urinary collagen crosslinks
o	Urinary calcium/creatinine (fasting)
-	Indices of bone formation
o	Serum total or bone-specific alkaline phosphatase (present in cells that line biliary pathways, also in osteoblasts)
o	Serum calcium – normal
o	Serum PTH - Normal

Question 8

7. List the complications of Paget’s disease

Answer 8

Musculoskeletal

• Skeletal pain
• Bone deformity
• Pathological fractures
• Secondary OA (common)

Neural

• Nerve compression (eg CTS, sensorineural deafness)
• Radiculopathy
• Spinal stenosis and myelopathy

Cardiovascular

• Increased cardiac output
• Congestive heart failure
• Generalised atherosclerosis
• Aortic valve calcification
• Endocardial calcification

Neoplastic
- Osteosarcoma (10-30x more common than normal)