Paget's disease (bone)

From Ganfyd

Sir James Paget first described chronic inflammation of bone as osteitis deformans in 1877, later becoming known as Paget's disease. This is a chronic disorder of the skeleton in which localised areas of bone become hyperactive. Normal matrix is replaced with softened and enlarged bone. After osteoporosis, Paget's disease is the second most common metabolic bone disease and is the commonest cause of bone dysplasia. However, approximately 70-90% of patients appear asymptomatic.

Aetiology

• Unknown but fair genetic component mostly associated with ubiquitin binding in the RANK/NF-κB signalling pathway.
  • Susceptibility is associated with mutations in genes encoding components of the RANK/NF-κB signalling pathway.^[1]
  • Genes definitely implicated in some patients with unknown associations near 5q31 and 10p13
    • Sequestosome 1(p62)^[2]
    • Valosin-containing protein deficits^[3]
• Virus like particles
  • ?paramyxovirus/measles virus/canine distemper virus/respiratory syncytial virus.
• Juvenile Paget's disease is a extremely rare genetic condition with similarities, often due to osteoprotegerin deficiency.^[4]

Incidence & Prevalence

• Middle age
• Males > Females
• Possibly associated with European stock/lifestyle given distribution centered on Western Europe, North America and Australasia.
• About 1% over 40 in U.S.A^[5]

Symptoms

• Usually asymptomatic and discovered incidentally by:
  • Plain radiography of bones
  • Assessment of raised alkaline phosphatase

Signs

• Skeletal expansion or distortion

Consider malignant transformation in Paget's when Constant worsening bone pain New mass Sudden fracture

• Bone pains and aches (often worse at night)
• Raised (bone isoenzyme) alkaline phosphatase
• Deafness and rarely hydrocephalus, nerve or other compression from bone expansion
• Pathological fracture
• Hypervascular bone causing
  • Warmth over bone
  • High output heart failure
• Sarcoma (rare less than 1%), usually osteosarcoma

Possible associations

• Calcification of arteries and heart valves
• Renal tract stones
• Peyronie's disease

Investigations

• Radiology is usually diagnostic (main differential diagnosis in adult men metastatic carcinioma of prostate)
• Bone scan for distributuin

Pathology

Bone:

• Cortical thickening - hyperostosis
• Disorganised coarse trabeculae - osteosclerosis
• Expansion

Treatment

• Bisphosphonates
• Calcitonin
• Orthopaedic appliances

External links

• National Association for the Relief of Paget's Disease (UK)[1].
• eMedicine chapter.

References