Practice Essentials
Heterotopic ossification (HO) was originally described in 1692 by Guy Patin, the Doyen of the Faculté de Médecine de Paris. Patin described a condition he observed in children and called myositis ossificans progressiva. The next major development in the history of HO came in 1918 as a consequence of military injuries sustained during World War I. Dejerine and Ceillier described a condition they referred to as paraosteoarthropathy, which they observed in patients with paraplegia caused by gunshot wounds to the spinal cord.
These older terms for HO have been superseded, but the terms ectopic ossification and myositis ossificans are used interchangeably with the term heterotopic ossification. The condition may affect the bones or the joints. Three types of HO have been described, as follows:
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Myositis ossificans progressiva (a rare pediatric metabolic disease whereby skeletal muscle ossifies)
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Neurogenic HO (this occurs as a result of burns or neurologic injury)
Traumatic HO is the focus of this article.
Alternatively, pathologic bone formation surrounding the bones and joints can be defined histologically. HO is the formation of mature lamellar bone in nonosseous tissue, whereas myositis ossificans is a specific type of HO that occurs in inflammatory muscle. Both of these processes are examples of ectopic ossification, and they may coexist, though they are distinct from periarticular calcification, which is the deposition of pyrophosphates within the soft tissues surrounding the joints.
After arthroplasty, HO can be noted in one of two ways. The condition can be a cause of physical symptoms, notably pain and stiffness, or it may be entirely asymptomatic and may be detected radiologically on follow-up films.
HO is seldom excised, because pain relief is often inadequate and improvement in range of motion (ROM) may not last. In established cases of HO following total hip arthroplasty (THA), excision may be performed. Patients may find that their ROM improves, but pain relief is likely to be limited. Pharmacologic agents and irradiation have been used for prophylactic purposes.
Further animal model studies are likely to provide greater understanding of HO and its management. These studies may involve research with the use of transgenic mice and bone morphogenic protein (BMP) as reliable genetic animal models. [3] Gene and protein expression studies are likely to be required to investigate HO on a cellular level.
In the future, reducing the incidence of symptomatic HO may be possible and may be achieved with improved surgical techniques whereby tissue trauma is reduced and the local operative environment is less favorable to the production of HO.
The use of selective cyclooxygenase (COX)-2 inhibitors, with improved side-effect profiles, is likely to replace the use of nonselective agents. [4, 5, 6] In turn, selective prostaglandin inhibitors may replace these agents, as it seems plausible that prostaglandin E2 is important in the pathogenesis of HO. Some evidence suggests that radiation therapy (RT) is safe and effective in the prophylaxis of HO [7] ; further research is required to define its role more precisely.
Anatomy
Operative treatment of HO is difficult and thus seldom performed, because pain relief is poor and improvements in ROM may not be sustained. Removal of heterotopic bone is technically difficult because the abnormal bone does not confine itself to the normal tissue planes. Furthermore, normal anatomic landmarks may be obscured. Consequently, to visualize the HO so that it can be excised, an extensile surgical exposure is required.
The HO itself is typically fragile and friable and not readily removed from the soft tissues; it is embedded and blended into the soft tissues. Surgical removal may involve substantial blood loss and incomplete excision, and the risks of recurrence are high. Surgeons attempting the procedure need to be familiar with the relevant surgical approaches to the affected region and to understand how to safely enlarge and extend the wounds.
Pathophysiology
Like the etiology (see below), the pathophysiology of HO is not completely understood. Once the osteogenic cells are stimulated, they begin to form osteoid, which in turn develops into mature HO. The underlying process is thought to be an inflammatory process in response to local tissue trauma. [8]
BMP is believed to be important in regulating the development of HO. The heterotopic bone is metabolically very active and contains more osteoblasts than ordinary bone. In addition, the tissue does not follow anatomic tissue planes and is generally more diffuse in nature than normal bone. The presence of the HO surrounding the bones and joints may affect the function of the normal soft tissues around them. Cases of HO causing ankylosis have been reported.
Etiology
The etiology of HO is, to some extent, determined by the type. The rare autosomal dominant condition myositis ossificans progressiva accounts for the inherited metabolic disease in children. Neurogenic HO may occur after head injury, spinal cord injury, infections of the central nervous system (CNS) such as tetanus and polio, CNS tumors, multiple sclerosis, and cerebrovascular accidents. Traumatic HO, the main topic of this article, can be caused by trauma (iatrogenic or other) to bones and joints.
The etiology of traumatic HO remains to be fully defined. Several theories have been advanced. Migrated bone marrow cells have been suggested as a potential cause of osteogenesis in connective tissue. Alternatively, muscle lesions or interstitial hemorrhagic foci have been suggested as a potential cause of muscle degeneration, perivascular connective tissue proliferation, and subsequent bone metaplasia.
A further theory has considered that periosteal damage could induce a differentiation of periarticular osteogenic cells. However, various models exist, and it is thought that the following three conditions must be met for HO to develop:
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Osteogenic precursor cells must be present
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An inductive stimulus should exist
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The local tissue environment should be favorable; the osteogenic precursor cells are thought to be pluripotential mesenchymal cells that are stimulated to differentiate into osteoblasts
A systematic review that included 25 studies and one conference abstract (N = 3940) identified the following patient-related risk factors for HO developing after acetabular fracture [9] :
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Increased body mass index (BMI)
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Male sex
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Greater age
Injury-related factors included the following [9] :
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Intensive care unit (ICU) admission and length of stay
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Non-ICU hospitalization for longer than 10 days
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Mechanical ventilation required for 2 days or longer
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Abdominal or thoracic injuries
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Number and type of associated fractures
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Traumatic brain injuries
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T-type acetabular fractures
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Pelvic ring injuries
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Hip dislocation
Care-related factors included the following [9] :
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Delay to surgery
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Extensile and posterior surgical approaches to the hip
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Trochanteric osteotomy
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Postoperative step-off greater than 3 mm
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Delay to prophylaxis after injury or surgery
Epidemiology
Traumatic HO occurs in 10-20% of predisposed patients. After THA and acetabular fracture surgery, the incidence can be 2-63%. HO apparently does not readily complicate nonoperative treatment of acetabular fractures; case series report this complication only in surgically treated cases. Implant-related series have shown an incidence of 8-90% following cementless THA, though many of the cases are asymptomatic. For distal humeral fractures and proximal humeral arthroplasty, the incidence can be 10-90%.
The incidence is the same in case series from the United States and Europe. Following total knee arthroplasty (TKA), the incidence of HO can be as high as 32%. In revision TKA, the incidence can be as high as 56%.
Bal et al examined the incidence of HO in 121 patients who underwent THA performed with a minimally invasive two-incision technique. [10] Of the 121 patients, 32 (26.5%) developed HO, as follows: Brooker grade I, 16 patients; Brooker grade II, 9 patients; Brooker grade III, 6 patients; and Brooker grade IV, 1 patient.
Some case series have suggested that HO occurring as a complication of THA tends to affect men more often than women (with a 3:1 male-to-female ratio possibly as high as 3:1), and it is more likely to occur if osteophytosis was a feature of the underlying degenerative joint disease. Other case series have shown that although men tend to be affected more often than women, women with HO experience more pronounced symptoms.
Prognosis
If HO is excised, improvements in functional ROM can be expected, though they may not last, and those patients who have pain from the HO may not have complete resolution of these symptoms. Alkaline phosphatase (ALP) levels may be used to indicate osteoblastic activity and can be used to assess the development of HO in the postoperative phase.
The results of one study concluded that regardless of etiology, significant gains in ROM are achieved with surgical excision of heterotopic bone around the elbow. A higher recurrence rate was observed in patients with CNS injuries as compared with patients with localized trauma. [11]
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Brooker I heterotopic ossification associated with an uncemented total hip arthroplasty.
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Brooker I heterotopic ossification associated with a cemented total hip replacement that has undergone acetabular component augmentation and fixation of the greater trochanter.
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Brooker II heterotopic ossification associated with a right cemented total hip replacement. On the left side, an uncemented total hip arthroplasty is present with no heterotopic ossification.
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Brooker III heterotopic ossification associated with a left uncemented total hip arthroplasty.
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Brooker I heterotopic ossification associated with a revision hip arthroplasty.
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Brooker II heterotopic ossification associated with a right revision hip arthroplasty.
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Brooker I heterotopic ossification associated with bilateral revision hip arthroplasties.
