Key Facts

Paget disease of bone (osteitis deformans) is a focal disorder of bone remodelling with excessive osteoclastic resorption followed by disorganised osteoblastic new bone formation, resulting in structurally weak, expanded, and deformed bone.

Epidemiology

• Prevalence: ~1–2% of over-55s in the UK (declining)
• More common in Northern England and Lancashire
• Male:female ratio ~1.5:1
• Rare before 40 years

Aetiology

• Unknown; likely combination of genetic (SQSTM1/p62 mutations) and environmental (paramyxovirus — debated)
• First-degree relatives: 7× increased risk

Pathophysiology

• Three phases:
  1. Osteolytic (early): excessive osteoclast activity → lytic lesions
  2. Mixed: osteoblasts respond but form disorganised woven bone
  3. Sclerotic (late): dense but structurally abnormal bone
• Disorganised collagen pattern (mosaic/jigsaw pattern on histology)
• Increased vascularity in pagetic bone → high-output cardiac failure (if extensive disease)

Most Commonly Asymptomatic (~70%)

• Incidental finding: raised ALP on blood tests, or X-ray abnormality

Symptomatic

• Bone pain: deep, aching, constant; worse at night and at rest
• Deformity: bowing of long bones (tibia — sabre tibia), skull enlargement (increasing hat size)
• Fractures: pathological fractures through pagetic bone
• Neurological compression: deafness (CN VIII compression by skull base expansion), other cranial nerve palsies, spinal cord compression (spinal canal narrowing)
• Increased warmth over affected bone (hypervascularity)

Complications

• Osteosarcoma (~1%): sudden worsening of pain, soft tissue mass, rapid ALP rise
• High-output cardiac failure: extensive polyostotic disease
• Hypercalcaemia: during immobilisation
• Osteoarthritis: joints adjacent to pagetic bone

Red Flags

• Sudden increase in pain or ALP (osteosarcoma)
• Neurological deficit (cord/nerve compression)
• Heart failure symptoms (high-output)

Bloods

• ALP: markedly elevated (often >1000 IU/L in extensive disease) — most useful marker
• Calcium and phosphate: NORMAL (helps distinguish from metastases, hyperparathyroidism)
• Bone-specific ALP, P1NP: more specific bone formation markers
• U&Es, LFTs: to confirm ALP is of bone origin

Imaging

• X-ray: characteristic features depending on phase
  • Lytic: V-shaped/flame-shaped advancing front
  • Mixed/sclerotic: expanded bone, thickened cortex, coarsened trabecular pattern
  • Skull: cotton wool appearance
  • Tibia: sabre tibia (anterior bowing)
• Isotope bone scan: shows extent of disease (identifies all affected sites)
• CT/MRI: if neurological compression or suspected sarcomatous change

Special Tests

• Biopsy: only if diagnostic uncertainty or suspected malignant transformation
• Audiometry: if skull involvement

Non-pharmacological

• Education and reassurance (many asymptomatic — observe)
• Physiotherapy and exercise
• Walking aids if deformity/pain
• Hearing aids if deafness

Pharmacological

Indications for treatment: bone pain, neurological complications, preparation for surgery on pagetic bone, active disease at high-risk sites (skull, weight-bearing bones)

• Zoledronic acid 5mg IV single dose: most effective; induces remission in ~90%; often sustained for years
• Risedronate 30mg OD for 2 months: oral alternative
• Pamidronate IV: alternative if zoledronic acid contraindicated
• Calcium and vitamin D supplementation during bisphosphonate treatment
• Calcitonin: historical; rarely used now (replaced by bisphosphonates)

Surgical/Interventional

• Joint replacement: secondary OA
• Fracture fixation: pathological fractures
• Neurosurgical decompression: cord/nerve compression

Referral Criteria

• Rheumatology/metabolic bone: symptomatic Paget, treatment decisions
• ENT/audiology: hearing loss
• Neurosurgery: spinal cord compression
• Oncology: suspected sarcomatous transformation

• Most patients have good prognosis with mild disease
• Zoledronic acid: induces biochemical remission in ~90% for several years
• Osteosarcoma: ~1% risk; very poor prognosis (5-year survival <20%)
• High-output heart failure: rare, only with extensive disease
• Deafness: often progressive; may partially respond to bisphosphonates if treated early
• Quality of life: good for most patients; bone pain is main source of morbidity

Paget Disease Biochemistry vs Differentials