Paget's disease

Question 1

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

Answer 1

• Monostotic (15%) – Tibia, femur, skull, vertebrae, humerus

- Polyostotic (85%) – spine, pelvis, femur, skull, sacrum, tibia, humerus

Question 2

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

Answer 2

1. Osteolytic phase
   - Normal bone resorbed by abnormal osteoclasts (more numerous, larger and more nuclei than normal)
   - Bone turnover increases up to 20x normal (net bone loss)
   - Results in “flame” lesions on radiograph
2. Mixed osteolytic-osteoblastic
   - Uncoupled and excessive bone destruction (osteoclasts) and woven bone formation (osteoblasts)
   - Woven bone replaces normal bone due to lag in mineralization
   - Bone volume remains approximately normal
   - Bone becomes highly vascularised
   - 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
   - Decrease in osteoclastic activity with continued woven bone formation (osteoblasts) leads to increased density (“sclerosis”)
   - Eventually, osteoblastic activity also decreases and condition becomes quiescent
   - Aka “burn-out” phase – minimal/absent bone resorption and formation
   - 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 and microscopic features of pagetic bone

Answer 3

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

Macroscopic (seen in osteosclerotic 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 clinical manifestations of Paget’s disease

Answer 4

• 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 5

Discuss the radiological and laboratory diagnosis of Paget’s disease

Answer 5

Radiological

• 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 at area under stress (thins elsewhere) 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)

Lab
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 6

List the complications of Paget’s disease

Answer 6

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)