Osteopetrosis and Pagets

Osteopetrosis (Marble Bone Disease)


Osteopetrosis is characterized by increased bone sclerosis due to deficient osteoclast activity, leading to brittle yet sclerotic bones.

Types of Osteopetrosis

  1. Autosomal Recessive (Infantile Malignant)
    • Severe form, often leading to death in infancy.
  2. Autosomal Dominant (Benign)
    • Also known as Albers-Schonberg disease.
    • Typically diagnosed incidentally after a fracture or X-ray.

Diagnosis

  • Diagnosis of the benign type is usually incidental, especially after fractures or cranial X-rays.
  • Additional findings may include:
    • Anemia
    • Cranial nerve palsies, such as hearing loss.

Histology

  • Osteoclasts lack the typical ruffled border.
  • Presence of calcified bars within mature trabeculae.

X-ray Features

  • Loss of medullary cavities due to sclerosis.
  • Bone within a bone appearance.
  • Symmetric, uniform sclerosis.

Treatment

  • Interferon
  • Bone marrow transplant for the malignant infantile type.

Paget’s Disease of Bone


Paget’s disease is a metabolic disorder involving overactivity of osteoclasts and osteoblasts, leading to abnormal bone formation.

Epidemiology

  • Men are slightly more affected.
  • Common in regions such as the USA and UK.
  • Increases with age: affects 3% of people over 40 years and 10% over 80 years.

Types

  1. Monostotic: Affects one bone (20% of cases).
  2. Polystotic: Affects multiple bones (80% of cases).

Causes

  • Viral-induced: Linked to paramyxovirus, respiratory syncytial virus, and canine distemper virus.
  • Genetic: Some hereditary predisposition.

Pathophysiology

  • Initial problem lies in osteoclasts, which increase in size and number, becoming overactive.
  • Osteoblasts respond by increasing activity, leading to accelerated but disorganized bone formation.

Phases of Paget’s Disease

  1. Lytic Phase: Dominated by osteoclast activity, causing bone lysis.
  2. Active Phase: Osteoblast activity increases, resulting in mixed sclerotic and lytic areas.
  3. Burnt-out Phase: Residual effects of the active stage; the bone appears coarse with a mosaic-like trabeculae.

Clinical Presentation

  • Asymptomatic in 95% of cases, with many diagnoses being incidental.
  • Fractures: Slower healing fractures, requiring fixation.
  • Arthritis: Commonly affects the hip and knee, leading to protrusio acetabuli.
  • Bone Pain: Uncommon but can indicate high turnover or malignancy (e.g., osteosarcoma).
  • Nerve Compression: Spinal stenosis or hearing loss.
  • Deformities: Bowing of long bones (e.g., Sabre tibia).
  • Cardiac Failure: Due to high vascularity of the bone.
  • Gout: Due to increased protein metabolism.
  • Malignant Transformation: Increased risk of osteosarcoma.

X-ray Features

  • Widened bones: A compensatory response.
  • Pathologic/stress fractures.
  • Blade/flame sign: Seen in the lytic stage.
  • Mosaic-like pattern: Mixed sclerotic and lytic areas.
  • Deformities and secondary osteoarthritis.
  • Hip protrusio: Protrusion of the acetabulum into the pelvic cavity.

Laboratory Findings

  • Normal calcium levels.
  • Elevated alkaline phosphatase: Reflects increased osteoblast activity.
  • Elevated acid phosphatase: Reflects increased osteoclast activity.
  • Urinary collagen peptides and hydroxyproline: Indicate high collagen turnover.

Histology

  • Mosaic-like bone marrow.
  • Scanty cells.

Bone Scan

  • Shows high uptake in areas of active disease.

Treatment Options

Treatment is indicated for: - Pathologic fractures - Bone pain - Nerve/spinal compression - Osteoarthritis - Cardiac failure due to high output - Gout - Pre-surgery to reduce bleeding risk.

Medical Treatment

  1. Bisphosphonates: Inhibits osteoclast overactivity.
  2. Calcitonin: Less commonly used due to side effects.

Surgical Treatment

  • Fracture fixation is preferred due to long healing times.
  • Arthroplasty: For joint involvement.
  • Nerve decompression: In cases of nerve compression.
  • Malignant transformation treatment: For osteosarcoma or other sarcomas.

Malignant Transformation

  • 30x increased risk of osteosarcoma, especially in long-standing polystotic disease.
  • May also develop fibrosarcoma or chondrosarcoma.
  • Prognosis: 50% survival rate for osteosarcoma.
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