Heterotopic ossification

Heterotopic ossification may occur following head or spinal cord trauma, burns, or major surgery on the musculoskeletal system.

A heterotrophic bone may cause severe physical impairment by surrounding a joint such as the hip or the elbow and fixing the joint in a nonfunctional position (i.e., contracture).

Heterotopic ossification is also very common following open reduction and internal fixation of acetabular fractures.

Heterotopic ossification Pathophysiology

Heterotopic ossification is the process of bone formation in extraskeletal soft tissue. Roberts in 1968 was first to note the association between head trauma and periarticular ectopic bone formation, and others have since demonstrated a positive correlation between the extent of head trauma and functional heterotopic ossification severity.

The pathogenesis of heterotopic ossification following head injury is uncertain. However, recent theories suggest that head trauma causes an increase in inflammatory mediators and bone morphogenic proteins, which induce soft tissue osteoprogenitor stem cells to differentiate into osteoblasts.

Increased serum levels of prostaglandin E2 after head trauma are also believed to play a role in the proliferation of differentiated osteoblasts.

The osteoblasts secrete osteoid peripherally about the area of trauma within 7 to 10 days. Primitive cartilage appears after 14 days, and trabecular bone forms within 2 to 5 weeks. Mature lamellar bone in the periphery surrounding immature and undifferentiated central tissues is present by the sixth week.

Plain radiographs and computerized tomography scans show a very characteristic zoning pattern of mature bone at the periphery and a lucency in the center. The lucent area represents immature musculoskeletal tissues.

Heterotopic ossification Clinical Features

The hip is the most commonly involved joint, followed by the elbow, shoulder, and knee. The incidence of heterotopic ossification of the hip following head trauma varies from 11% to 76%, with ankylosis of the joint occurring in 11% to 20% of those patients.

Clinical signs that should cause one to suspect heterotopic ossification include pain and decreased range of motion at the joint, as well as inflammatory markers such as fever, erythema, swelling, and warmth at the joint.

Making the diagnosis is also dependent on identifying patients who are more likely than others to develop heterotopic ossification. Risk factors include male gender, underlying systemic disorders such as ankylosing spondylitis and diffuse idiopathic skeletal hyperostosis, previous heterotopic bone formation, and limb spasticity.

The diagnosis of heterotopic ossification is typically made based on clinical suspicion and radiographic findings, which appear within the first 3 to 6 weeks after injury.

Brooker devised the classification system that is most frequently used to radiographically grade the amount of heterotopic ossification at the hip.

Class I includes islands of bone within the soft tissue that is located about the hip. Class II consists of bone spurs from the pelvis or proximal femur leaving at least 1 cm between opposing bone surfaces.

Class III allows for less than 1 cm between opposing bone surfaces, and class IV is apparent ankylosis of the hip in the anterior-posterior view. Triple-phase radionucleotide bone scan is the preferred method for early detection. It will show increased blood flow and increased concentration of the tracer within the soft tissue of the hip before any findings are apparent on radiographs.

Computed tomography is most commonly used to define the areas of involvement. Although serum alkaline phosphatase does not have diagnostic or prognostic value, levels correlate with the degree of ongoing ossification, and thus it used as a marker for active disease.

Heterotopic ossification Treatment

Nonsteroidal anti-inflammatory drugs (NSAIDS), external beam radiation, and disphosphonates have been used with varying success for prophylaxis against heterotopic ossification.

In a randomized, double-blind, prospective study, 400 mg of ibuprofen three times daily administered within 48 hours of the injury and given for 8 days was found to be effective. Indomethacin has also been used for prophylaxis and is dosed at 75 to 100 mg/day for 7 to 14 days.

However, patient compliance with NSAIDs is of concern because of the incidence of gastrointestinal distress. Ionizing radiation has been shown to inhibit osteogenesis. A recent meta-analysis comparing single-dose radiation with NSAIDs found radiotherapy to be more efficacious.

A one-time dose of 700 to 800 cGy is recommended within 24 hours of trauma or 72 hours postoperatively. Although the risk of inducing malignant disease with radiotherapy exists, it is uncommon at such low doses.

Finally, disphosphonates are pyrophosphate analogues that delay mineralization of osteoid by inhibiting the growth of hydroxyapatite crystals. They have not been shown to be effective and carry the risk of osteomalacia with long-term use.

Definitive heterotopic ossification treatment once it has developed and become symptomatic is surgical excision followed by adjuvant therapy to decrease the likelihood of recurrence.

Excision occurs with the intention to improve function because patients can become severely limited in their activities of daily living. However, surgery must wait until the lesion has matured.

Active, ongoing ossification is an absolute contraindication. Thus, excision must await the radiographic appearance of well-defined cortex and normal serum levels of alkaline phosphatase.

This typically occurs around 18 months after the injury. Other indicators for successful excision are good cognitive recovery following head trauma and good motor control of the extremity. Postoperative radiation therapy is recommended to prevent recurrence.

Suggested Readings

Garland DE, Blum CE, Waters RL. Periarticular heterotrophic ossification in head injured adults. Incidence and location. J Bone Joint Surg Am 1980;

Morrey BF, ed. Joint Replacement Arthroplasty. New York: Churchill Livingstone, 1991

Sarafis KA, Karatzas GD, Yotis CL. Ankylosed hips caused by heterotrophic ossification after traumatic brain injury: a difficult problem. J Trauma 1999;

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