What is heterotopic ossification (heterotopic calcifications)?

Heterotopic Ossification

Heterotopic ossification (HO) is the formation of lamellar bone in soft tissues where bone normally does not exist, occurring due to impaired cellular mechanisms that lead to abnormal bone formation outside the skeletal system. 1

Types and Causes

Heterotopic ossification can be classified into two main categories:

1. Acquired Heterotopic Ossification

• Common causes:
  • Musculoskeletal trauma
  • Central nervous system disorders (brain injuries, tumors, encephalitis)
  • Spinal cord injuries
  • Following orthopedic surgeries (particularly hip arthroplasty)
  • Burns
  • Explosion injuries 1, 2, 3

2. Hereditary Forms

• Fibrodysplasia Ossificans Progressiva (FOP)

  • Characterized by congenital malformations of the great toes and progressive heterotopic endochondral ossification
  • Caused by mutations in ACVR1 gene (activating mutation c.617G>A; p.R206H)
  • Follows specific anatomic patterns (axial > appendicular; dorsal > ventral; proximal > distal)
  • No documented cases of malignancy in FOP patients 4

• Other hereditary forms:

  • Progressive osseous heteroplasia
  • Albright's hereditary osteodystrophy 1

Clinical Manifestations

• Joint swelling, pain, and movement disorders
• Heat, edema, and local flushing
• Reduced range of motion
• In early stages: fever, erythema, and joint tenderness (can mimic cellulitis, osteomyelitis, or thrombophlebitis)
• In advanced stages: severe spasticity and potential ankylosis
• Most commonly affects hips, knees, and elbows 2, 5, 6

Imaging Characteristics

Radiography

• Initial imaging modality of choice for chronic pain potentially related to HO
• Can detect heterotopic ossification, osteochondral lesions, and soft tissue calcification 4

CT Scan

• Useful for assessment of heterotopic ossification, loose bodies, and osteophytosis
• High sensitivity (93%) for detection of loose bodies 4

MRI

• Less sensitive than radiographs in detecting heterotopic ossification/calcification
• Useful for evaluating associated soft tissue injuries 4

Bone Scan

• Extremely sensitive for detection of HO
• Early phase can identify inflammatory component
• Delayed images demonstrate increased tracer uptake due to bone formation
• Serial quantitative bone scans help time surgical intervention 4, 2

Pathogenesis

The exact pathogenesis remains unclear, but involves:

• Inflammatory processes
• Mesenchymal stem cells (MSCs) following an osteogenic program
• Abnormal cellular signaling pathways 3

Prevention and Treatment

Prevention

• Non-steroidal anti-inflammatory drugs (NSAIDs, such as indomethacin)
• Bisphosphonates (such as ethane-1-hydroxy-1-diphosphate)
• Local radiation therapy
• Molecular biological interventions (experimental stage) 2, 5

Treatment

1. Surgical Resection

   • Most effective treatment for established HO
   • Should be timed appropriately (after maturation) to avoid recurrence
   • Serial bone scans help determine optimal timing 2, 5

2. Conservative Management

   • Physical therapy
   • Anti-inflammatory medications
   • In some cases, casting or immobilization 6

3. Adjuvant Therapies

   • NSAIDs
   • Bisphosphonates
   • Radiation therapy 5, 6

Clinical Considerations and Pitfalls

1. Differential Diagnosis:

   • Must be distinguished from metastatic calcifications (seen in hypercalcemia)
   • Differentiate from dystrophic calcifications in tumors 1
   • Early HO can mimic infection or thrombophlebitis 2

2. Timing of Intervention:

   • Premature surgical resection before lesion maturation increases risk of recurrence
   • Serial imaging helps determine optimal timing 2

3. Impact on Rehabilitation:

   • HO can severely compromise rehabilitation in already incapacitated patients
   • May lead to increased contractures, spasticity, pressure ulcers, and pain 1

4. Special Populations:

   • In patients with FOP, avoid unnecessary trauma as it can trigger flare-ups
   • Patients with brain or spinal cord injuries require close monitoring for HO development 4, 2

Heterotopic ossification represents a significant complication that can substantially impact quality of life, particularly in patients already dealing with serious primary conditions. Early recognition and appropriate management are essential to minimize long-term functional impairment.