Definition

Heterotopic ossification is the formation of mature, lamellar bone in nonskeletal tissue, usually in soft tissue surrounding joints [1,2]. Its exact etiology is unknown. Heterotopic ossification is commonly seen in patients with traumatic brain injury, spinal cord injury, cerebrovascular accident, burns, fractures, trauma, or muscle injuries and after total joint arthroplasty. Heterotopic ossification has also been described in medically complex patients after prolonged sedation, ventilation, critical illness, and immobilization [3,4]. In addition, heterotopic ossification has been found to be a complication after both cervical and lumbar disc replacement [5,6]. Riedel first described heterotopic ossification after trauma to the spinal cord in 1883 [7]. The term neurogenic heterotopic ossification has been commonly used for heterotopic ossification in patients with traumatic brain injury, spinal cord injury, and cerebrovascular accident [2,8]. The bone formation in heterotopic ossification differs from that in other disorders of calcium deposition in that heterotopic ossification results in encapsulated bone between muscle planes, which is not intra-articular or connected to periosteum [9].

The incidence rate reported in the literature varies from 11% to 75% in patients with severe traumatic brain injury and spinal cord injury [10,11]. Approximately 33% of patients with traumatic brain injury and spinal cord injury diagnosed with heterotopic ossification show a loss of joint range of motion; 10% to 16% progress to complete joint ankylosis [2,10]. The incidence of heterotopic bone formation after total hip arthroplasty and acetabular fracture is estimated at 16% to 53% and 18% to 90%, respectively [12].

Heterotopic ossification is both more common and more extensive in patients with severe spasticity. Increased spasticity and lower level of limb function increase the risk for development of heterotopic ossification and the rate of recurrence after surgical resection [8]. In addition, when other factors are controlled for, the incidence of heterotopic ossification increases with body mass index in patients with acetabular fracture [13]. In patients with spinal cord injury, the number of pressure ulcers and duration of time since injury are also associated with the development of heterotopic ossification [14]. When ectopic bone is discovered in patients with paraplegia, it is never found above the level of injury. Heterotopic ossification is rarely seen in flaccid limbs [8]. Interestingly, heterotopic ossification is infrequently reported in cerebral palsy or in children with anoxic brain injury [2].

The pathogenic mechanisms of heterotopic ossification are still being investigated. Whether genetic factors or local phenomena (trauma, tissue hypoxia, venous insufficiency, edema) are triggering factors, the final common pathway is inflammation and increased blood flow in the tissues [1,8,15]. Undifferentiated mesenchymal cells in connective tissue surrounding muscle or vasculature are transformed by bone morphogenetic proteins into osteoblasts, which lay down new bone matrix [4,12,13,15–17]. The scientific literature suggests that overactive bone morphogenetic protein signaling is involved in the development of both acquired heterotopic ossification and congenital heterotopic ossification, which is seen in fibrodysplasia ossificans progressiva.

The temporal relationship between injury and initiation of ossification is not clear. However, clinical signs, symptoms, and positive diagnostic test results may appear as early as 2 weeks after injury [12]. Mineralization and true bone formation are usually completed by 6 to 18 months [8]. The extent of bone formation has been described in the Brooker classification [2,11,17–19] for heterotopic ossification of the hip (Fig. 130.1). Only class III and class IV are clinically significant. Although modifications to the Brooker classification have been suggested, many clinicians continue to use this system to describe the extent of heterotopic bone formation (Table 130.1).

Symptoms

Individuals demonstrate great variability in the initial symptoms and degree of heterotopic bone involvement. Patients are often asymptomatic [1,20]. In neurogenic heterotopic ossification, the most common symptom is pain (although this is often absent in spinal cord injury because of sensory deficits). Limitation to joint range of motion is commonly reported [8,12]. Symptoms range in onset from 2 weeks to 12 months after the inciting event, and patients may report warmth, swelling, and tenderness [2,11,21,22]. Heterotopic ossification may trigger autonomic dysreflexia in patients with spinal cord injury at or above the T6 level [23].

Physical Examination

Time at onset, location, and degree of heterotopic bone formation vary between individuals. Therefore, joints should be examined frequently in those at risk to assess range of motion and to assist in early diagnosis. The clinician should also inspect each joint for erythema and palpate for point tenderness or masses. The most common physical finding is decreased range of motion of the joint.

Distal joints of the hands and feet are almost never involved. Heterotopic ossification is typically limited to hips, knees, shoulders, and elbows [8]. In neurogenic heterotopic ossification secondary to traumatic brain injury or spinal cord injury, the hip is the most common joint affected [15]. Ossification is usually found inferomedial to the joint and is typically associated with adductor spasticity [2].

Functional Limitations

The loss of range of motion secondary to heterotopic ossification interferes with hygiene, transfers, and daily activities [22]. Pain from heterotopic ossification can be a significant cause of functional limitation.

Diagnostic Studies

The three-phase bone scan is the current “gold standard” for early detection of heterotopic ossification. It is possible to discover increased metabolic activity as early as 2 to 4 weeks after injury. This procedure involves intravenous injection of technetium Tc 99 m–labeled polyphosphate, which is known to accumulate in areas of active bone growth. The three phases are as follows [8,22] (Fig. 130.2):

Phase 1: Dynamic blood flow occurs immediately after injection.

Phase 2: Immediate static scan detects areas of blood flow after injection.

Phase 3: Static phase involves a repeated bone scan after several hours.

A disadvantage of the three-phase bone scan is its lack of specificity. It therefore may be difficult to differentiate bone tumor, metastasis, or osteomyelitis from heterotopic ossification [8]. In addition, false-negative bone scans have been described after spinal cord injury [24].