Paget's Disease of Bone
Summary
Paget's disease of bone is a chronic disorder of bone remodelling characterised by excessive osteoclastic bone resorption followed by disorganised osteoblastic bone formation. This results in enlarged, deformed, and weakened bones. It is usually asymptomatic and discovered incidentally on X-ray or from an isolated raised alkaline phosphatase (ALP). When symptomatic, it causes bone pain, deformity, fractures, and complications related to bone enlargement (e.g., deafness from skull involvement). Treatment is with bisphosphonates, which reduce bone turnover and pain. The most serious complication is malignant transformation to osteosarcoma (rare, <1%).
Key Facts
- Pathology: Excessive bone resorption then chaotic formation
- Typical Patient: >55 years; often asymptomatic
- Key Bloods: Isolated raised ALP (Calcium and Phosphate usually normal)
- X-Ray: Lytic and sclerotic changes, cortical thickening, "cotton wool" skull
- Treatment: Bisphosphonates (Zoledronate IV or Risedronate oral)
- Complication: Osteosarcoma (<1%)
Clinical Pearls
"Raised ALP, Normal Calcium": The classic blood picture. Raised ALP reflects increased osteoblastic activity. Calcium and phosphate are usually normal unless immobilised.
"Cotton Wool Skull": The classic X-ray appearance of skull Paget's - patchy sclerotic lesions.
"Sabre Tibia": Anterior bowing of the tibia is characteristic of Paget's.
"Increased Hat Size": Skull involvement causes skull thickening - patients notice they need a larger hat.
Prevalence
- 2-3% of >55 years (UK)
- More common in Northern Europe
Demographics
- M:F = 1.8:1
- Age: >55 years (rare before 40)
- Often familial (15-30%)
Declining Incidence
- Incidence declining in many countries (reason unclear)
Phases of Paget's Disease
| Phase | Features |
|---|---|
| Lytic (Osteoclastic) | Excessive bone resorption |
| Mixed | Resorption and formation |
| Sclerotic (Osteoblastic) | Disorganised bone formation |
Result
- "Woven bone" — Structurally weak, disorganised
- Increased vascularity
- Enlarged, deformed bones
Aetiology
- Unknown
- Possible viral trigger (measles? paramyxovirus?)
- Genetic: SQSTM1 mutations in familial cases
Asymptomatic (70-80%)
Symptoms
| Feature | Notes |
|---|---|
| Bone pain | Deep, aching; worse at night; at affected site |
| Deformity | Bowing of long bones (tibia, femur) |
| Fractures | Pathological; "chalk-stick" transverse fractures |
| Increased head size | Skull involvement |
| Deafness | Ossicle involvement or cranial nerve compression |
| Warmth over bone | Increased vascularity |
Sites Affected (in order)
- Pelvis (most common)
- Spine
- Femur
- Skull
- Tibia
Inspection
- Bowing deformity (tibia, femur)
- Skull enlargement
- Kyphosis
Palpation
- Warmth over affected bones
- Tenderness
- Bony enlargement
Complications to Assess
- Hearing (whispered voice, tuning fork)
- Vision (compression)
- Neurological deficit (spinal stenosis)
Bloods
| Test | Finding |
|---|---|
| ALP | Raised (often markedly) |
| Calcium | Usually normal |
| Phosphate | Usually normal |
| Bone markers (P1NP, CTx) | Elevated (not routine) |
Imaging
| Modality | Findings |
|---|---|
| X-ray | Mixed lytic/sclerotic; Cortical thickening; "Cotton wool" skull; "V-shaped" advancing lytic wedge in long bones |
| Bone scan (Isotope) | Increased uptake at affected sites; Shows extent of disease |
| CT/MRI | If spinal compression, sarcoma suspected |
Management Approach
┌──────────────────────────────────────────────────────────┐
│ PAGET'S DISEASE MANAGEMENT │
├──────────────────────────────────────────────────────────┤
│ │
│ ASYMPTOMATIC (No treatment usually): │
│ • Monitor ALP periodically │
│ • Consider treatment if affecting weight-bearing bone │
│ or high risk of complications │
│ │
│ SYMPTOMATIC: │
│ • Bisphosphonates (reduce bone turnover and pain) │
│ • First-line: Zoledronic acid 5mg IV (single infusion) │
│ • Alternative: Risedronate 30mg daily for 2 months │
│ • Simple analgesia for pain │
│ │
│ MONITORING: │
│ • ALP normalisation (aim for 50% reduction) │
│ • Symptom improvement │
│ • Repeat treatment if relapse (usually years later) │
│ │
│ COMPLICATIONS: │
│ • Hearing loss: Audiology referral │
│ • Fractures: Orthopaedic management │
│ • Spinal stenosis: Surgery if necessary │
│ • Osteosarcoma: Urgent oncology referral │
│ │
└──────────────────────────────────────────────────────────┘
Of Paget's Disease
- Fractures (chalk-stick, transverse)
- Osteoarthritis (secondary to deformity)
- Deafness (skull involvement)
- Spinal stenosis (nerve compression)
- High-output cardiac failure (rare; increased bone vascularity)
- Osteosarcoma (<1%; but high mortality)
- Hypercalcaemia (if immobilised)
Warning Signs for Osteosarcoma
- Sudden increase in pain
- Rapid swelling
- Rising ALP after previously stable
With Treatment
- Bisphosphonates highly effective
- ALP normalises in most
- Pain improves
- May prevent complications
Long-Term
- Usually well-controlled
- Relapse possible (years later)
- Osteosarcoma rare but serious
Key Guidelines
- Paget's Association UK: Management Guidelines
- NICE CKS: Paget's Disease of Bone
Key Evidence
Bisphosphonates
- Zoledronic acid highly effective; single infusion duration
What is Paget's Disease?
Paget's disease is a condition where the normal cycle of bone breakdown and rebuilding becomes disrupted. The bone is replaced too quickly and the new bone is weaker and larger than normal.
Who Gets It?
It mainly affects older adults (over 55) and is more common in the UK and Northern Europe. It often runs in families.
What Are the Symptoms?
Many people have no symptoms. When symptoms occur, they include:
- Bone pain (often worse at night)
- Bones becoming bent or enlarged (especially the legs or skull)
- Hearing loss (if the skull is affected)
- Fractures
How is It Diagnosed?
- Blood test showing raised alkaline phosphatase (ALP)
- X-rays showing typical bone changes
- Bone scan to see which bones are affected
How is It Treated?
- Bisphosphonates: Medication to slow down bone turnover (often a single injection of zoledronic acid)
- Pain relief: Paracetamol or anti-inflammatories
- Most people only need one treatment and symptoms improve
Primary Guidelines
- Paget's Association. Clinical Guidelines for the Diagnosis and Management of Paget's Disease of Bone.
Key Studies
- Reid IR, et al. Comparison of single infusion of zoledronic acid with risedronate for Paget's disease (Horizon-PFT). N Engl J Med. 2005;353(9):898-908. PMID: 16135834