Heterotopic Ossification

Nora Cullen, Christina Taggart, and Cassandra Cowie

GENERAL PRINCIPLES

Heterotopic ossification (HO) is a common sequela of traumatic brain injury (TBI) that can lead to pain and restricted joint range of motion (ROM), limiting a patient’s ability to participate in rehabilitation and further adding to disability by reducing mobility and function.

Definition

The abnormal formation of mature lamellar bone within soft tissues such as tendons, ligaments, and muscles [1].

Epidemiology

The incidence of HO following TBI is 11% to 73.3%, reaching clinical significance in 10% to 20% of cases [2].

Classification

After Brooker et al. [3]:

• Class I—Islands of bone in the soft tissue

• Class II—Bone spurs leaving at least 1 cm between opposing surfaces

• Class III—Bone spurs leaving less than 1 cm between opposing surfaces

• Class IV—Ankylosis

Etiology

While HO is seen in rare genetic conditions, it is most prevalent after trauma (TBI, traumatic spinal cord injury, burns) and joint replacement surgery [4].

Pathophysiology

Neurogenic Factors

Osteoblastic cells undergo inappropriate differentiation within soft tissues. They are likely stimulated by an osteogenic factor released by the injured brain [5–8], which affects prostaglandins (PG) and bone-morphogenetic proteins (BMPs), leading to abnormal regulation of bone metabolism [9]. Other contributing factors include hypercalcemia, hypoxia, sympathetic imbalance, and disequilibrium of parathyroid hormone and calcitonin [10].

Enhanced Osteogenesis

Ectopic bone is highly metabolically active, with a rate of formation three times greater and an osteoclastic density twice that of normal age-matched bone [11]. Timeline: The ectopic organic osteoid matrix reaches full calcification within a matter of weeks. Osseous reorganization to mature trabecular bone occurs during subsequent months [5].

DIAGNOSIS

Early detection is imperative in preventing the progression of HO.

Risk Factors

There is an increased risk with skeletal trauma, spasticity, immobilization, postinjury coma greater than 2 weeks, and a longer period of mechanical ventilation or intubation [5,12,13].

Clinical Presentation

Restricted joint ROM, joint swelling and warmth, and joint pain [14]. The presence of a firm palpable mass is a late stage clinical sign [5].

Timing

• HO formation precedes symptom onset; decreased ROM is often the earliest clinical sign.

• Symptoms generally begin 2 months postinjury, but range from 2 weeks to 12 months [1].

• The condition may occur later with other, nontraumatic, precipitating circumstances (e.g., fracture, surgery) [15–17].

Location

HO can occur at any joint following TBI but most often develops at fracture sites or in bruised soft tissue. The most commonly affected joints in the absence of fracture are the hip, shoulder, elbow, and knee [13,14]. A single joint is affected in ~40% of patients; in another third, two joints are affected [2]. Ankylosis is most likely to occur at the elbow.

Physical Examination

Clinical exam often reveals a swollen, warm, and tender joint, with decreased ROM. Other findings may include erythema, para-articular mass, and fever.

Differential Diagnosis

These clinical findings may be mistaken for deep venous thrombosis, infection, local trauma, or fracture [18], all of which should be considered in the differential diagnosis of HO.

Bloodwork

• Elevated serum alkaline phosphatase (SAP) levels can occur from 7 weeks before [6] to 3 weeks after [19] appearance of clinical symptoms.

• Ethrocyte sedimentation rate (ESR) and C-reactive protein (CRP) may also become elevated early in the formation of HO [20].

Radiography

• Triple-phase bone scan with increased uptake during first and second phases is the diagnostic gold standard. HO can be detected as soon as clinical features appear [6].

• Plain radiographs may remain negative until 2 to 6 weeks after clinical symptoms begin [21].

MANAGEMENT

The aim is prevention of progression, pain management, and maximization of joint mobility.

Physical Modalities

• Physiotherapy involving assisted ROM exercises and gentle stretching is of benefit in relieving pain, maintaining mobility, and preventing ankylosis [6,22]. The joint should not be moved beyond its pain-free range of movement [23].

• Manipulation under anaesthesia may help differentiate between spasticity and ankylosis and relax muscles enough to perform forceful manipulation, increasing ROM [24].

• Continuous passive motion can increase and maintain joint ROM both during HO development and after surgical excision [25].

Medical Management

Nonsteroidal Anti-Inflammatory Drugs [26]

Action. Minimize HO formation and patient discomfort in early and intermediate stages.

Mechanism. Most nonsteroidal anti-inflammatory drugs (NSAIDs) act as nonselective inhibitors of cyclooxygenase, thereby blocking the formation of PG.

Optimal Drug. Indomethacin

• Indomethacin is the gold standard in the prevention of HO following total hip arthroplasty (THA). Other NSAIDs, such as naproxen and diclofenac, have been shown to be equally effective and are considered alternative first-line treatments.

• Cyclooxygenase-2 inhibitors, such as rofecoxib and celecoxib, can also be used.

Potential Side Effects of NSAIDS. Gastrointestinal complications, cardiovascular side effects, delayed fracture healing.

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