Abstract
Heterotopic ossification is a pathologic condition resulting in the formation of bone in soft tissue, typically surrounding the joints. Heterotopic ossification may be genetic, neurogenic, or traumatic. It is most commonly seen in patients with spinal cord injury, traumatic brain injury, severe burn patients, or following total hip arthroplasty. Three factors required for heterotopic ossification include a progenitor stem cell, a stimulating event, and a supportive environment. Heterotopic ossification is often asymptomatic but may present as decreased range of motion at the involved joint, local pain, localized warmth, edema, erythema, or fever. Heterotopic ossification typically involves hips, knees, shoulders, or elbows and almost never involves distal joints of the hands or feet. Loss of range of motion due to heterotopic ossification can result in impaired hygiene, transfers, and daily activities. The three-phase bone scan is the gold standard for early diagnosis. Treatment options include physical therapy, nonsteroidal anti-inflammatory medications, bisphosphonates, radiation therapy, and surgical excision. The timing for surgical resection is often delayed due to concern of recurrence. Excessive heterotopic ossification may cause a number of complications including fusion of joints and compression of peripheral nerves.
Keywords
Bisphosphonates, brooker classification, heterotopic ossification, myositis ossificans
| Synonyms | |
| |
| ICD-10 Codes | |
| M61.9 | Calcification and ossification of muscle, unspecified |
| M61.20 | Paralytic calcification and ossification of muscle, unspecified site |
| M61.10 | Myositis ossificans progressiva, unspecified site |
| M61.00 | Myositis ossificans traumatica, unspecified site |
| M61.40 | Other calcification of muscle, unspecified site |
| M89.30 | Hypertrophy of bone, unspecified site |
Definition
Heterotopic ossification (HO) is a pathologic condition resulting in the formation of lamellar bone in soft tissue, typically surrounding joints. HO may be genetic, neurogenic, or traumatic. Genetic forms of HO, which include fibrodysplasia ossificans progressiva and progressive osseous heteroplasia, are rare but potentially life-threatening disorders. Neurogenic forms of HO occur commonly as complications of traumatic brain injury, spinal cord injury, or cerebrovascular accident. Traumatic forms occur after burns, fractures, muscle injuries, or following total joint arthroplasty. HO has also been reported following cervical and lumbar disc replacement and in medically complex patients who require prolonged mechanical ventilation and immobilization. Pathologic soft tissue calcifications can be classified as dystrophic or metastatic. Metastatic calcifications represent diffuse calcifications resulting from elevated calcium phosphate product such as may occur in renal failure or hyperparathyroidism. HO is a type of dystrophic soft tissue calcification. The presence of trabecular pattern of bone differentiates HO from other forms of dystrophic calcification.
HO was first described by German physician Riedel in 1883 and later by French physicians Dejerne and Ceillier, utilizing the term “paraosteoarthropathy” in observations of patients with traumatic paraplegia during World War I. HO has many different names in the medical literature, including paraosteoarthropathy, myositis ossificans, periarticular ectopic ossification, neurogenic osteoma, neurogenic ossifying fibromyopathy, and heterotopic calcification. The bone formation in HO differs from that in other disorders of calcium deposition in that HO results in encapsulated bone between muscle planes, which is not intra-articular or connected to periosteum.
The incidence rate for HO varies significantly in the medical literature, depending upon the etiology and the means of detection. The incidence for HO following total hip arthroplasty without prophylaxis is 25% to 40%. The incidence in spinal cord injury ranges from 10% to 53%. Clinically significant HO in traumatic brain injury is reported at 10% to 20%. Incidence in severe burns ranges from 0.1% to 6%. Stroke patients develop HO in 0.5% to 1.2% of cases.
The most common location for neurogenic HO is the hip, followed by shoulder and elbow. In spinal cord injury patients, HO occurs only caudal to the level of injury. In stroke patients with HO the paretic side is affected in 70% of cases. Severe burns can precipitate development of HO in any major joint. The elbow is the most frequently involved joint, independent of the proximity of the burn. Risk factors for developing HO following total hip arthroplasty include previous HO or osteoarthritis with extensive osteophytes. Male gender is also a risk factor for developing HO after total hip arthroplasty. It is unclear if the increased risk is due to the observation that male patients are more likely than female patients to have hypertrophic osteoarthritis or if there is another explanation. There is no evidence that use of cemented prosthesis and total hip arthroplasty increase the risk of HO. For patients with acetabular fractures, increased risk for clinically significant HO include use of iliofemoral surgical approach, T-type fractures, associated abdominal and/or chest injuries, presence of operative findings suggestive of severe local injury (e.g., femoral head damage, sciatic nerve damage, intra-articular bone fragments), and the need for prolonged mechanical ventilation. Mourad’s retrospective study of 395 patients who underwent surgical repair for displaced acetabular fractures shows significant increased incidence of HO in patients with increasing body mass index (31% for BMI greater than 30) despite prophylactic measures (radiation therapy with or without indomethacin). The risk of male spinal cord injured patients for developing HO is five times higher than for females. The presence of spasticity, the completeness of injury, the presence of pressure ulcers, and the co-occurrence of traumatic brain injury are all identified as risk factors for development of HO in spinal cord injury patients. Larson showed an increased prevalence of histocompatibility antigen HLA–B27 in spinal cord injured patients with HO. Prolonged levels of unconsciousness, spasticity, decerebrate posturing, and diffuse axonal injury are well identified risk factors for developing HO in the traumatic brain injury patient. Interestingly, HO is infrequently reported in cerebral palsy or in children with anoxic brain injury.
Pathogenic mechanisms of HO are not clearly defined. Three factors are felt to be necessary for HO to occur. These factors include a progenitor stem cell that can differentiate into an osteo-chondrogenic cell, a stimulating event, and a supportive tissue environment that allows osteogenesis. The specific cellular origin of HO remains unknown. Although there have been some observations that suggested cells of ectodermal or endodermal origin can contribute to HO, the preponderance of evidence supports mesenchymal progenitor cells as the population of cells most likely to contribute directly to HO. Mesenchymal stem cells alone however cannot produce HO. Bone morphogenic proteins, growth hormone, prolactin, insulin-like growth factor type I, substance P, and basic fibroblast growth factor have all been implicated as stimulating factors. Various factors and local tissue environment are thought to support the development of HO. These factors include disturbance of the microvasculature, changes in oxygen tension, and changes in local pH (from acid to alkaline enhancing precipitation of bone salts). Genet’s model of spinal cord injury induced HO in mice strongly supports the role of inflammation and phagocytic macrophage recruitment as a dominant supporting factor in development of HO. The temporal relationship between injury and initiation of ossification remains unclear. Clinical signs, symptoms, and positive diagnostic tests may appear as early as 3 weeks after injury. HO following traumatic brain injury usually manifests 4 to 12 weeks after injury. HO in spinal cord injury is usually diagnosed between 1 and 6 months post injury with a peak at 2 months. Mineralization and true bone formation are usually completed by 6 to 18 months. The extent of bone formation has been described in the Brooker classification for HO of the hip ( Fig. 131.1 ). Only class III and class IV are clinically significant ( Table 131.1 ).
| Class | Description |
|---|---|
| I | Islands of bone within soft tissue |
| II | Bone spurs from pelvis or proximal femur, at least 1 cm between bone surfaces |
| III | Bone spurs from pelvis or proximal femur with space between bone surfaces of less than 1 cm |
| IV | Apparent bone ankylosis of the hip ( Fig. 131.1 ) |
Symptoms
HO is often asymptomatic and is discovered as an incidental finding on a radiograph. When HO is symptomatic, it commonly causes decreased range of motion at the involved joint, local pain, and if located superficially, the patient may report localized warmth, mild edema, and erythema. Fever may also be associated with HO. HO growth may cause blood vessel compression and present as a swollen extremity. Advanced HO may also entrap a peripheral nerve and present with symptoms of neuropathy.
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. HO is typically limited to hips, knees, shoulders, and elbows. Less frequently reported sites include the ankle and temporomandibular joints. In neurogenic HO secondary to traumatic brain injury or spinal cord injury, the hip is the most common joint affected. Ossification is usually found inferomedial to the joint and is typically associated with adductor spasticity. The elbow is the most frequently affected joint in either thermal or electrical burn patients. Although HO is predominantly found in articular locations, it has been reported in soft tissue not surrounding joints in the setting of muscle contusions from trauma and abdominal wounds after surgery.
Diagnostic Studies
The three-phase bone scan is the current “gold standard” for early detection of HO. 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 ( Fig. 131.2 ) :
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.
