Paget’s Disease

Background/Epidemiology

• Common; incidence rises with age; estimated up to 8% of people 85 or over
• Characterised by focal areas of disorganised bone remodelling

Aetiology

• Genetic component- ~15% have a family history; mutations of the sequestosome 1 gene (SQSTM1) have been shown to be important
• Paramyxovirus infections (e.g. measles; RSV) are potentially triggers (although the exact association is debated)

Pathophysiology

• Lytic Phase
  • Rapid increase in bone resorption by osteoclasts, followed by an increase in osteoblastic activity in response
    • The new bone produced by the osteoblasts is poorly organised, structurally weak and highly vascular (osteoblast activity is excessive in an attempt to keep up with osteoclast activity)
      • increased vascularity and formation of arteriovenous shunts can cause an increase in cardiac output to compensate
      • can also cause a degenerative arthritis
• Intermediate phase
  • As osteoclastic activity decreases, there becomes a point where osteoclast and osteoblast activity equalise and bone remains fairly stable
• Sclerotic/Blastic phase
  • Eventually, osteoclastic activity burns out and osteoblastic activity persists, and woven (unorganised) bone is replaced by lamellar bone.  After this, disease becomes quiescent.
• Although it can affect any bone in the body, Paget’s tends to affect the axial skeletal, long bones and the skull

Presentation

• Classically, bone pain, deformity (particularly of the long bones e.g. femur; and the skull), deafness (not due to compression of the auditory nerve but conduction impairment due to otosclerosis), osteo-(degenerative) arthritis and pathological fractures
  • Many patients won’t present with all (or any) features and can be diagnosed by incidental x-ray
  • Other features include other cranial nerve palsies, radiculopathy, spinal cord compression/spinal stenosis
  • Patients have a small risk of developing osteosarcoma

Investigations

• Bone biochemistry
  • Raised Alk Phos
  • May have normal calcium and normal-low phosphate
  • Vitamin D may be normal
• X-ray
  • Bone expansion, with alternating areas of radiolucency and osteosclerosis (woven bone)
• Radionuclide scanning
  • Highlights areas of active disease
  • Identify the extent of disease

Management

• Bisphosphonate treatment (for active disease)
  • Make sure to correct any vit D and calcium deficiency prior to treatment to avoid hypocalcaemia
  • If pain does not improve with bisphosphonates, it is likely that pain is actually due to a complication e.g. osteoarthritis, fracture etc
• Calcitonin can also be used
• NSAIDs may be useful for pain