Paget’s disease (Osteitis deformans)

Definition:

• Is a disorder of bone remodelling
• There is excessive resorption with a subsequent compensatory increase in new bone formation
• The new bone is structurally abnormal and therefore weak, with secondary phenomenon like:
• Increased local bone blood flow
• Fibrous tissue in adjacent bone marrow

Epidemiology:

• Most often seen in Europe (and particularly northern England)
• Affects both men and women over age 40 years
• Up to 10% of adults are radiologically affected by the age of 90

Aetiology and pathogenesis:

• Some evidence suggests a viral aetiology, for which canine distemper virus, measles and respiratory syncitial virus have been proposed
• The osteoclasts are more numerous than normal and contain an increased number of nuclei
• Bone resorption is chaotic and the is a haphazard (rather than linear) deposition of collagen fibres, leading to ‘woven’ bone formation
• Bone mineralization is normal
• The structure of unaffected bone is normal and continues to remain so. Thus, Paget’s disease doesn’t spread

Clinical features:

• 60-80% of patients with radiological evidence of Paget’s are asymptomatic
• The disease may be monostotic or polyostotic
• Most common sites of involvement are:
• Femur
• Pelvis
• Tibia
• Skull
• Lumbosacral spine

When symptomatic, features can include:

• Bone pain (most often in the spine or pelvis)
• Apparent joint pain (when an affected bone is close to a joint, leading to cartilage damage and osteoarthritis)
• Deformities (especially, bowed tibia and skull changes)
• Complications from:
• Nerve compression (most commonly CN VIII)
• Increased bone blood flow (cardiac hypertrophy, high-output cardiac failure)
• Weakness of the abnormal bone

• Osteogenic sarcoma (rare, <1%)

Investigations:

X-rays:

• Bone enlargement/expansion
• Osteolytic lesions
• Sclerosis and thickening of bone trabeculae in long bones and vertebrae

Bone scans

Biochemistry:

• Increased serum ALP (a marker of bone formation)
• NORMAL serum Ca²⁺ and PO₄^3-

Measurements of bone resorption:

• Increased 24-hour urinary hydroxyproline excretion

Treatment:

Oral bisphosphonates:

• E.g. Alendronate 10-40mg daily for 6 months
• Responses to bisphosphonates are long-lasting, with 50-70% reduction in serum ALP. The new bone formed is lamellar, not woven

Other bisphosphonates:

• IV pamidronate has been used widely as a single or multiple infusion

Calcitonin:

• Inhibit bone resorption and turnover but are extremely expensive
• Side-effects include:
• Flushing
• Nausea

• Nasally administered calcitonin has fewer side-effects

Surgery:

• Joint replacement or osteotomy are sometimes necessary
• Neurosurgery where there is spinal disease