What is Paget's Disease of Bone?

Paget's Disease of Bone (PDB) is a chronic disorder of abnormal bone remodeling. In affected bones, there is excessive breakdown (resorption) and disorganized rebuilding, resulting in bones that are enlarged, weak, deformed, and prone to fractures.

How Common is it?

• Affects 1-3% of adults over age 50
• More common in older adults (peak age 70-80)
• More common in people of European descent (especially Northern Europe)
• Slightly more common in men

Cause:

• Unknown, but likely multifactorial
• Genetic: ~15-30% have a family history; mutations in SQSTM1 gene
• Environmental: Some theories involve slow viral infection (measles, respiratory syncytial virus)—unproven

What Happens in Paget's Disease?

1. Excessive Bone Resorption: Overactive osteoclasts break down bone rapidly
2. Chaotic Bone Formation: Osteoblasts try to rebuild bone but do so in a disorganized, "mosaic" pattern
3. Result: Bones become enlarged, structurally abnormal, weak, and prone to fractures and deformities

Which Bones Are Affected?

Can affect one bone (monostotic) or multiple bones (polyostotic). Most commonly:

• Pelvis (70%)
• Spine (50%)
• Skull (40%)
• Femur, Tibia (Long bones of legs - 30%)

Symptoms:

Many patients are ASYMPTOMATIC (diagnosed incidentally on X-ray or lab tests)

Symptomatic Patients May Have:

• Bone Pain: Deep, aching; worse at night
• Bone Deformities:
  • Bowing of legs (tibia, femur)
  • Enlarged skull, prominent forehead
  • Curved spine (kyphosis)
• Fractures: Bones are weak despite being enlarged
• Arthritis: Adjacent joints (hip, knee) develop osteoarthritis from abnormal mechanics
• Neurological Complications:
  • Hearing Loss: Skull involvement compresses auditory nerves
  • Nerve Compression: Spine involvement can cause spinal stenosis, radiculopathy
• Warmth Over Affected Bone: Increased blood flow

Complications:

• Fractures
• Osteoarthritis
• Hearing Loss (if skull involved)
• Heart Failure: Rare; increased blood flow through pagetic bone can strain the heart (high-output heart failure)
• Osteosarcoma: Rare but serious; bone cancer in pagetic bone (<1%)< /li>
• Hypercalcemia: Rare; if immobilized or with extensive disease

Diagnosis:

Labs:

• Alkaline Phosphatase (ALP): MARKEDLY ELEVATED (best screening test; reflects bone turnover)
• Bone-Specific ALP: More specific if total ALP elevated
• Calcium and Phosphorus: Usually normal
• Bone Turnover Markers: Elevated (CTX, NTX, P1NP)—research/monitoring

Imaging:

• X-rays (Diagnostic):
  • Enlarged, thickened bones
  • Coarsened trabecular pattern ("cotton wool" appearance in skull)
  • Bone expansion, deformities
  • Lytic (lucent) or sclerotic (dense) areas
• Bone Scan (Nuclear Medicine):
  • Identifies ALL affected bones (useful in polyostotic disease)
  • Shows increased uptake in pagetic bones
• MRI or CT: To assess complications (fractures, nerve compression, sarcoma)

Treatment:

Indications for Treatment:

• Symptomatic disease (bone pain)
• Involvement of weight-bearing bones (to prevent fractures/deformities)
• Involvement of skull (to prevent neurologic complications)
• Elevated ALP >2x upper limit of normal
• Planned orthopedic surgery on affected bone (to reduce bleeding)

Asymptomatic patients with mild disease may not need treatment—just monitoring

Bisphosphonates (First-Line):

• Zoledronic Acid (Reclast®): 5 mg IV once (single dose); most effective
  • Normalizes ALP in 90% of patients
  • Effects last years
• Alendronate (Fosamax®): 40 mg daily for 6 months (oral)
• Risedronate (Actonel®): 30 mg daily for 2 months (oral)

Calcitonin (Second-Line):

• Less effective than bisphosphonates
• Used if bisphosphonates not tolerated
• Nasal spray or injection

Supportive Care:

• Pain Management: Acetaminophen, NSAIDs
• Physical Therapy: Maintain mobility, strengthen muscles
• Assistive Devices: Cane, walker if needed
• Surgery: For fractures, severe arthritis (joint replacement), nerve decompression

Monitoring:

• Alkaline Phosphatase: Every 3-6 months after treatment (goal: normalize or reduce by ≥75%)
• X-rays: Baseline and periodically to assess disease progression or complications
• Bone Scan: If extent of disease unclear
• Audiometry: If skull involvement (hearing loss screening)

Prognosis:

• Most patients respond well to bisphosphonates
• Disease is chronic but manageable
• Complications (fractures, deformities, hearing loss) can significantly impact quality of life
• Osteosarcoma is rare but has poor prognosis