M08.026.003 Paget disease (Osteitis deformans)

Paget disease, also known as osteitis deformans, is a chronic bone disorder affecting the normal remodeling process. It leads to excessive bone resorption followed by disorganized bone formation, resulting in weak and deformed bones. This section delves into the causes, clinical features, diagnosis, and complications of Paget disease, providing crucial information for medical students.

Description

Paget disease is a localized disorder affecting specific bone areas. It disrupts the natural cycle of bone breakdown and replacement, leading to:

• Excessive bone resorption by osteoclasts (cells responsible for breaking down bone).
• Disorganized bone formation by osteoblasts (cells responsible for building new bone).

This unbalanced process creates thickened but weak bones prone to fractures and deformity.

Possible Causes:

• Association with paramyxovirus (a type of virus) has been suggested.
• Mutations in the SQSTM1 gene may play a role.

Epidemiology:

• Typically affects individuals over 40 years old.
• More common in people of European ancestry.
• Most commonly involves the skull, pelvis, femur (thigh bone), and vertebrae (spinal bones).
• Usually affects multiple bones (polyostotic) and presents with mild symptoms.

Stages of Paget Disease:

The disease progresses through three stages:

1. Osteolytic Stage: Dominated by increased osteoclast activity, leading to bone breakdown.
2. Mixed Osteolytic-Osteoblastic Stage: Both bone resorption and formation occur.
3. Osteosclerotic Stage (Burnout Stage): Predominated by osteoblast activity, resulting in thickened but weak bone.

Clinical Features

Paget disease can present with various symptoms, including:

• Bone pain and deformity
• Fractures, especially in weight-bearing bones
• Warmth of the skin overlying affected bone due to increased blood flow (hypervascularity)

Diagnosis:

• X-rays typically show enlarged bones with areas of bone breakdown (lytic) and bone formation (sclerotic).
• Lab tests may reveal:
  • Highly elevated serum alkaline phosphatase (enzyme marker of bone activity)
  • Increased levels of urinary hydroxyproline (breakdown product of collagen)
• Bone scans can show increased uptake of radioactive material in affected areas.

Complications

Paget disease can lead to several complications, including:

• Arteriovenous shunts: Abnormal connections between arteries and veins within the affected bone marrow.
  • May cause high-output cardiac failure (heart struggles to pump blood efficiently).
• Increased risk of bone cancer: Paget disease is associated with a higher risk of osteosarcoma (bone cancer) and other sarcomas.

Microscopic Findings

Examination under a microscope reveals:

• A haphazard arrangement of cement lines (boundaries between old and new bone).
• This creates a “mosaic pattern” of lamellar bone (mature bone).
• Affected bones appear thickened but are structurally weak and fracture easily.

Skull Involvement:

• Paget disease involving the skull can lead to:
  • Increased head size (macrocephaly).
  • Narrowing of foramina (openings in the skull) compressing cranial nerves.
    • This can cause deafness and facial nerve palsy.
• Facial bone involvement may produce a characteristic “lion-like facies” due to bone enlargement.

Bibliography

• [Insert relevant medical textbook chapter on Paget disease]
• [Insert peer-reviewed journal article on recent advancements in Paget disease research]

Points to Remember:

• Paget disease is a chronic bone disorder causing bone resorption and disorganized bone formation.
• It primarily affects individuals over 40 and is more common in people of European descent.
• Common symptoms include bone pain, deformity, and fractures.
• Diagnosis involves X-rays, lab tests, and bone scans.
• Potential complications include high-output cardiac failure and increased risk of bone cancer.
• Early diagnosis and management are crucial to prevent complications.