Key Facts

Paget disease of bone (osteitis deformans) is a chronic condition of abnormal bone turnover resulting in enlarged, deformed, and weakened bones. It is the second most common metabolic bone disease after osteoporosis.

Epidemiology

• Prevalence: approximately 5% of the UK population aged >55 years
• More common in males (M:F = 3:2)
• Highest prevalence in Lancashire, UK (historically)
• Incidence is declining in the UK and other Western countries
• Rare before age 40

Aetiology

• Exact cause unknown; likely genetic and environmental factors
• SQSTM1/p62 gene mutations found in 40-50% of familial cases and 5-10% of sporadic cases
• Paramyxovirus (measles, canine distemper) inclusion bodies historically found in osteoclasts, though viral theory remains debated
• First-degree relatives have a 7-fold increased risk

Pathophysiology

• Increased osteoclast activity leads to excessive bone resorption
• Compensatory increase in osteoblast activity produces disorganised, woven bone
• Three phases: lytic (osteoclastic resorption) → mixed (resorption and formation) → sclerotic (predominantly osteoblastic)
• Affected bone is highly vascular, structurally weak despite increased size, and prone to deformity and fracture

Asymptomatic Disease

• 70-90% of patients are asymptomatic
• Often discovered incidentally through elevated ALP or characteristic X-ray findings

Bone Pain

• Deep, aching, constant pain worsening at night and with weight-bearing
• Most commonly affects pelvis (70%), femur, tibia, spine, and skull
• Pain may be due to increased vascularity, periosteal stretching, or secondary osteoarthritis

Bone Deformity

• Bowing of long bones (particularly tibia – sabre tibia)
• Skull enlargement – increasing hat size
• Kyphosis from vertebral involvement

Neurological Complications

• Sensorineural hearing loss (most common neurological complication) – due to cochlear involvement or compression of CN VIII
• Cranial nerve palsies
• Spinal stenosis with radiculopathy or cauda equina syndrome

Red Flags

• Sudden increase in pain or swelling → consider osteosarcoma (rare, <1%, but 30-fold increased risk)
• New neurological deficit → urgent imaging for spinal cord compression
• Rapid enlargement of a pagetic bone → exclude malignant transformation

Bedside

• Clinical examination: assess for bony deformity, warmth over affected bones, hearing assessment

Bloods

• Alkaline phosphatase (ALP): markedly elevated (often >1000 IU/L); primary marker of disease activity
• Calcium: usually normal (may be elevated with immobilisation)
• Phosphate: normal
• Bone-specific ALP or P1NP (procollagen type 1 N-terminal propeptide): more specific markers
• FBC, U&Es, LFTs to exclude other causes of raised ALP

Imaging

• X-ray: first-line imaging – shows osteolytic lesions, sclerosis, cortical thickening, bone enlargement, V-shaped advancing front (flame sign)
• Isotope bone scan (Tc-99m): identifies all affected sites; increased uptake in pagetic bone
• MRI: if neurological complications suspected or to assess for malignant transformation
• CT: useful for assessing spinal stenosis or surgical planning

Special Tests

• Urine N-telopeptide (NTx) or deoxypyridinoline: markers of bone resorption (less commonly used)
• Hearing audiometry: if skull involvement
• Bone biopsy: rarely needed; mosaic pattern of lamellar bone is pathognomonic

Non-pharmacological

• Weight management and regular exercise to maintain mobility
• Physiotherapy for gait abnormalities and joint protection
• Walking aids if lower limb deformity affects mobility
• Patient education (Paget's Association UK)

Pharmacological

• Bisphosphonates are first-line treatment:
  • Zoledronic acid 5mg IV single infusion (most effective; may provide remission for years)
  • Risedronate 30mg OD for 2 months (oral alternative)
  • Alendronate 40mg OD for 6 months (if risedronate not tolerated)
• Ensure adequate calcium (1000mg/day) and vitamin D (800 IU/day) supplementation before starting bisphosphonates
• Calcitonin (salmon calcitonin 100 IU SC/IM daily): rarely used, reserved for bisphosphonate intolerance
• Analgesia: paracetamol, NSAIDs for symptomatic pain

Surgical/Interventional

• Joint replacement for secondary osteoarthritis (hip most common)
• Osteotomy for severe bowing deformity
• Spinal decompression for neurological complications
• Pre-operative bisphosphonate treatment recommended to reduce vascularity

Referral Criteria

• Symptomatic disease or complications
• Suspected malignant transformation
• Neurological involvement
• Consideration for orthopaedic surgery

• Majority of patients have a normal life expectancy
• Osteosarcoma develops in <1% of cases but carries a 5-year survival of <20%
• High-output cardiac failure occurs in <5% with extensive disease
• Hearing loss affects approximately 30-50% of patients with skull involvement
• Single-dose zoledronic acid achieves biochemical remission in >95% of patients at 6 months
• Recurrence rate after zoledronic acid: approximately 0.5% per year

Phases of Paget Disease

Complications Summary

PRISM Trial

• Compared intensive vs. symptomatic treatment strategy
• Found no significant difference in fractures, pain, or quality of life at 3 years
• Questioned the benefit of treating asymptomatic patients to normalise ALP