Heterotopic ossification 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 heterotopic ossification came in 1918 because 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These older terms for heterotopic ossification have been superseded, but the terms ectopic ossification and myositis ossificans are used interchangeably with the term heterotopic ossification.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 heterotopic ossification have been described, as follows:
Myositis ossificans progressiva (a rare pediatric metabolic disease whereby skeletal muscle ossifies)
Neurogenic heterotopic ossification (this occurs as a result of burns or neurologic injury)
Traumatic heterotopic ossification (this follows injury to tissue surrounding the bones and joints)
Traumatic heterotopic ossification is the focus of this article.
Alternatively, pathologic bone formation surrounding the bones and joints can be defined histologically. Heterotopic ossification is the formation of mature lamellar bone in nonosseous tissue, whereas myositis ossificans is a specific type of heterotopic ossification that occurs in inflammatory muscle. Both of these processes are examples of ectopic ossification, and they may coexist, although they are distinct from periarticular calcification, which is the deposition of pyrophosphates within the soft tissues surrounding the joints.
Further animal model studies will be performed that will provide greater understanding of the condition and its management. These studies may involve research with the use of transgenic mice and bone morphogenic protein as reliable genetic animal models. Gene and protein expression studies are likely to be required to investigate heterotopic ossification on a cellular level.
In the future, reducing the incidence of symptomatic heterotopic ossification 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 heterotopic ossification.
The usage of selective cyclooxygenase-2 inhibitors, with improved side-effect profiles, is likely to replace the use of nonselective agents. [1, 2] In turn, selective prostaglandin inhibitors may replace these agents, as it seems plausible that prostaglandin E2 is important in the pathogenesis of heterotopic ossification. Further research will need to be carried out to ascertain the role of radiation therapy in the prophylaxis of heterotopic ossification.
Operative treatment of heterotopic ossification is difficult and thus seldom performed, because pain relief is poor and improvements in the range of movement 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 heterotopic ossification to excise it, an extensile surgical exposure is required.
The heterotopic ossification 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 how to safely enlarge and extend the wounds.
Like the etiology (see below), the pathophysiology of heterotopic ossification is not completely understood. Once the osteogenic cells are stimulated, they begin to form osteoid, which in turn develops into mature heterotopic ossification. The underlying process is thought to be an inflammatory process in response to local tissue trauma.
Bone morphogenic protein is believed to be important in regulating the development of heterotopic ossification. The heterotopic bone is known to be 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 heterotopic ossification surrounding the bones and joints may affect the function of the normal soft tissues around them. Cases of heterotopic ossification causing ankylosis have been reported.
The etiology of heterotopic ossification 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 heterotopic ossification 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 heterotopic ossification, the main topic of this article, can be caused by trauma (iatrogenic or other) to bones and joints.
The etiology of traumatic heterotopic ossification remains uncertain. During the past 50 years, a number of theories have been developed. 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 heterotopic ossification to develop:
Osteogenic precursor cells must be present
An inductive stimulus should exist
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
Traumatic heterotopic ossification occurs in 10-20% of predisposed patients. Following total hip arthroplasty and acetabular fracture surgery, the incidence can be 2-63%. Heterotopic ossification does not seem to readily complicate nonoperative treatment of acetabular fractures; case series only report this complication in surgically treated cases. Implant-related series have shown an incidence of 8-90% following cementless total hip arthroplasty, 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, the incidence of heterotopic ossification can be as high as 32%. In revision total knee arthroplasty, the incidence can be as high as 56%.
Bal et al examined the incidence of heterotopic ossification in 121 patients who underwent total hip arthroplasties performed with a minimally invasive two-incision technique. Of the 121 patients, 32 (26.5%) developed heterotopic ossification, 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 heterotopic ossification that occurs as a complication of total hip arthroplasty tends to affect men more often than women (perhaps as much as a 3:1 male-to-female ratio), 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 heterotopic ossification experience more pronounced symptoms.
If heterotopic ossification is excised, improvements in functional range of movement can be expected, though they may not last, and those patients who have pain from the heterotopic ossification may not have complete resolution of these symptoms. Alkaline phosphatase levels may be used to indicate osteoblastic activity and can be used to assess the development of heterotopic ossification in the postoperative phase.
The results of one study concluded that regardless of etiology, significant gains in range of motion 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.