Pagets disease

• chronic, progressive disturbance in bone metabolism that primarily affects older persons 
• Excessive reportion by osteoclasts, and compensatory but disorganized increase in bone formation by osteoblasts
• Progresses and deforms bones – local effects on bones, joints, nearby nerves

Epidemiology

• Onset over age 50 years
• Prevalence (United States)
  • Overall: 3%
  • Age over 80 years: 10%
• Ethnicity
  • Rare in Asia
  • Common in United States, Australia, and New Zealand

• Risks – increasing age, family history, caucasian
  • Consider family history screening ALP > 40 years

Differential Diagnosis

• Osteomalacia
• Osteoporosis
• Bone malignancies (primary or metastatic)
• Renal osteodystrophy
• Osteoarthritis
• Osteopenia
• Fibrous dysplasia

Pathophysiology

Causes:

• Genetic Factors: Strong genetic predisposition with associations to HLA markers. Siblings are at high risk.
• Environmental Factors: Possible viral involvement (paramyxoviruses like measles, canine distemper virus).
• Cytokine Involvement: Increased levels of IL-6 in bone marrow of patients.

• Phases
  • Phase 1: Intense Osteoclastic “hot” activity
    • Bone resorption predominates
    • Bone turnover is 20 times normal rate
  • Phase 2: Osteolytic-Osteoblastic activity
    • Woven bone formation
    • Ineffective mineralization
  • Phase 3: Dense bone deposition
    • Bone is disorganized and sclerotic
    • Weaker than normal bone

• Distribution
  • Pelvis (72%) 
  • Spine
    • Lumbar (58%)
    • Thoracic (45%)
    • Cervical (14%)
  • Skull (42%)
  • Long bones
    • Femur (55%)
    • Tibia (35%)
    • Humerus (31%)

Symptoms

(Asymptomatic in 70% of cases)

• Bone Pain: Commonly in spine, pelvis, femur.
• Joint Stiffness.
• Bone Deformities: Enlarged skull, bowing of long bones.
• Hearing Loss: Due to skull involvement.
• Fractures: Incomplete fractures in tibia and femur, often with minimal trauma.
• Neurological Complications: Cranial nerve neuropathies, spinal cord compression.
• Cardiac Complications: High-output heart failure, calcified aortic stenosis.

Signs

• Kyphosis
• Limb shortening or bowing
• Frontal forehead bossing
• Skull enlargement
• Loose teeth

Labs

• Alkaline Phosphatase
  • Total serum Alkaline Phosphatase
    • if raised without other cause e.g. Liver disease, vitamin D deficiency, hyperPTH 
    • is the most clinically useful indicator of disease activity in PDB. 
    • It is elevated in most untreated patients
    •  may be within the reference range in patients with monostotic or limited disease. 
  • Bone specific ALP if unsure 
• 25-hydroxyvitamin
  • osteomalacia may also present with bone pain and a raised alkaline phosphatase level
  • vitamin D deficiency should be corrected before bisphosphonate therapy to avoid the risk of hypocalcaemia

Radiology: XRay

• General changes
  • Trabeculation – sclerotic lines on Xray
  • Lytic changes
  • Commonly mixed lytic/sclerotic changes
• Skull changes
  • Osteoporosis circumscripta
• Long bone changes
  • Flame-shaped changes
  • Limb bowing
  • Fractures (banana-shaped transverse Fractures)

• Radiology: Nuclear bone scans to determine extent of disease 

Monitoring

• Screening if first degree relative has Paget’s Disease
  • Alkaline Phosphatase every 3 years (over age 50)
• Monitoring of diagnosed Paget’s Disease
• Alkaline Phosphatase every 3 to 12 months

Associated conditions

• Malignant degeneration (up to 10% of Paget’s Disease)
  • Osteosarcoma
  • Fibrosarcoma
  • Spindle cell Sarcoma
• Pseudomalignancy (Pseudosarcoma or pseudo giant cell)
• Osteoarthritis (Paget’s Disease involving joint)
• Nephrolithiasis
• Nerve compression syndromes from direct pressure
  • Hearing Loss
  • Spinal stenosis
  • Neuropathic pain, weakness or Paresthesias

Management

• Adequate pain control
• Calcium Supplementation 1500 mg qd
• Vitamin D 400 IU per day
• Low impact Exercise
• Avoid straining affected bone
• Suppress bone resorption (Osteoclasts)
  • bisphosphonates won’t prevent bony deformities, but may reduce complications 
  • Indications
    • Symptomatic patients
      • Pain in pagetic bones
      • Young < 50
      • Lesion at critical site – e.g. Skull, vertebrae
      • Active disease with high ALP
      • Neurological symptoms
      • Neurological complications
      • Significant osteolytic lesions
      • Involvement of long bones, vertebrae or base of skull
      • Before surgery involving pagetic bones
      • Significant joint involvement (eg. hip joint)
    • Alkaline Phosphatase >125 to 150% of normal
  • First line agents:
    • Bisphosphonates if symptomatic
      • Inhibit bone resorption
      • Single dose of zoledronic acid or short course of oral bisphosphonate can induce longer term remission
      • zoledronic acid – 1st line
        • Need to check vitamin D and calcium, GFR, ensure well hydrated
      • Risedronate 30mg for 2 months
      • Pamidronate 60mg infusion
  • Alternative agents (not as potent as Bisphosphonates)
• Calcitonin 100 U SC or IM qd for 6 to 18 months

• surgery
  • Secondary OA
  • Neurological secondary to spinal compression Cosmetic

Non-Pharm management

• Diet and Nutrition:
  • Adequate calcium and vitamin D intake: Ensure you are getting enough calcium and vitamin D in your diet, as these are essential for bone health. Dairy products, green leafy vegetables, fortified foods, and supplements can help meet your needs.
• Weight Management:
  • Maintaining a healthy weight: Achieving and maintaining a healthy weight can reduce the stress on your bones and joints, which is important when dealing with Paget’s disease.
• Physical Activity:
  • Weight-bearing exercises: Engaging in weight-bearing exercises like walking, hiking, dancing, and strength training can help improve bone density and strength. However, it’s essential to consult your healthcare provider before starting any new exercise regimen, as they can provide guidance on what activities are safe for your specific condition.
• Assistive Devices:
  • Use of assistive devices: If Paget’s disease has affected your mobility or caused joint pain, using assistive devices like canes, walkers, or orthopedic supports may help improve your quality of life.
• Pain Management:
  • Heat and cold therapy: Applying heat or cold packs to areas of pain or inflammation can provide temporary relief from discomfort.
  • Physical therapy: Physical therapy sessions may help improve joint mobility, reduce pain, and enhance muscle strength.
• Lifestyle Modifications:
  • Avoiding excessive alcohol: Excessive alcohol consumption can negatively affect bone health, so it’s advisable to limit alcohol intake.
  • Smoking cessation: Smoking can also have adverse effects on bone health, so quitting smoking is beneficial.
• Fall Prevention:
  • Home safety measures: Make your home safer by removing tripping hazards, installing handrails, and improving lighting to reduce the risk of falls.
• Regular Monitoring:
  • Follow-up appointments: Regularly visit your healthcare provider for check-ups and monitoring of your Paget’s disease to ensure it is well-managed and complications are detected early.
• Education and Support:
  • Education: Learn about Paget’s disease, its symptoms, and management strategies. Understanding your condition can empower you to make informed decisions and manage your health effectively.
  • Support groups: Consider joining support groups or seeking counseling to connect with others who have Paget’s disease. Sharing experiences and information with others can provide emotional support and practical insights.