You are in: eMedicine Specialties > Orthopedic Surgery > NEOPLASMS Traumatic Heterotopic OssificationArticle Last Updated: Nov 17, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 12
  Author: Chris McLean, MBBS, MRCS(Glasg), AFRCS(Ire), Specialist Registrar, Departments of Orthopedic and Trauma Surgery, Frimley Park Hospital, UK Chris McLean is a member of the following medical societies: British Medical Association Coauthor(s): Richard Hargrove, MBBS, FRCS(Ire), Orthopedic Specialist Registrar, Department of Trauma, St Georges University Teaching Hospital, London, UK; John B Wood, MBBS, FRCS(Ed), FRCS(Tr & Orth), Consulting Surgeon, Departments of Trauma and Orthopedic Surgery, University Hospital, Lewisham, UK Editors: Miguel A Schmitz, MD, Consulting Surgeon, Department of Orthopedics, Klamath Orthopedic and Sports Medicine Clinic; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Ian D Dickey, MD, FRCSC, Adjunct Professor, Department of Chemical and Biological Engineering, University of Maine; Consulting Staff, Adult Reconstruction, Orthopedic Oncology, Department of Orthopedics, Eastern Maine Medical Center; Dinesh Patel, MD, FACS, Associate Clinical Professor of Orthopedic Surgery, Harvard Medical School; Chief of Arthroscopic Surgery, Department of Orthopedic Surgery, Massachusetts General Hospital; Harris Gellman, MD, Consulting Surgeon, Broward Hand Center, Voluntary Clinical Professor of Orthopedic Surgery and Plastic Surgery, Departments of Orthopedic Surgery and Surgery, University of Miami School of Medicine Author and Editor Disclosure Synonyms and related keywords: heterotopic ossification, ectopic ossification, myositis ossificans, myositis ossificans progressiva, neurogenic heterotopic ossification, traumatic heterotopic ossification, paraosteoarthropathy, joint pain, periarticular calcification, ankylosis INTRODUCTIONSection 2 of 12
  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. The historical terms for heterotopic ossification have been superseded, but ectopic ossification and myositis ossificans are used interchangeably with the term heterotopic ossification.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: 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), and 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. FrequencyTraumatic 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, as 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, although 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%. 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. EtiologyThe etiology is, to some extent, determined by the type of heterotopic ossification. 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 such as tetanus and polio, central nervous system tumors, multiple sclerosis, and cerebrovascular accidents. Traumatic heterotopic ossification, the main topic of this article, can be caused by trauma, iatrogenic or otherwise, 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 3 conditions must be met in order for heterotopic ossification to develop:
PathophysiologyBecause the etiology is not entirely understood, it is not surprising that the pathophysiology is also 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. ClinicalFollowing arthroplasty, heterotopic ossification can be noted in 1 of 2 ways: the condition can be a cause of physical symptoms, notably pain and stiffness, or it may be entirely asymptomatic and detected radiologically on follow-up films. If a person has symptomatic heterotopic ossification, he or she may present with a loss in the range of movement in the affected joint. This may coexist with pain and soft-tissue swelling. As such, differential diagnoses of this clinical picture would include the following:
INDICATIONSSection 3 of 12
Heterotopic ossification is seldom excised, because pain relief is often inadequate and improvement in range of motion may not last. In established cases of heterotopic ossification following total hip arthroplasty, excision may be performed. The results of this procedure are varied. Patients may find that their range of movement improves, but pain relief is likely to be limited. Following trauma to the elbow, surgical excision may be indicated based on pain, nerve entrapment, and stiffness. In such procedures, the surgery may be beneficial as associated contractures are released, and their release can be as important as removal of the heterotopic ossification. The timing of surgery is controversial. Heterotopic ossification is often thought to take approximately 12 months to mature; however, surgery on posttraumatic heterotopic ossification at the elbow has been performed effectively at 3 and 6 months posttrauma. The pearls for surgery are the following:
RELEVANT ANATOMYSection 4 of 12
Operating on heterotopic ossification is difficult and thus seldom performed, because pain relief is poor and improvements in the range of movement may not be sustained. The 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. CONTRAINDICATIONSSection 5 of 12
As heterotopic ossification is seldom excised, a definitive list of surgical contraindications has not been established. However, excision should not be performed before the heterotopic ossification has matured, because incomplete and inadequate excision may result. Surgery on a joint that has wound sepsis or deep sepsis is contraindicated because the outcome is likely to be suboptimal under these circumstances. Because the outcome of surgery is unpredictable, the indications need to be carefully considered. Pain relief cannot be predicted reliably following excision of heterotopic ossification as a complication of total hip arthroplasty, whereas better results for improved range-of-movement arcs are more likely to occur. WORKUPSection 6 of 12
Lab Studies
Imaging Studies
Histologic FindingsWithin 1 week of the index trauma, heterotopic ossification commences with a spindle cell proliferation. Within a few days of the spindle cell proliferation, peripheral primitive osteoid develops. Two weeks after index trauma, primitive cartilage and woven bone develops. Trabecular bone begins to appear 2-5 weeks after the index trauma. If a biopsy is performed on heterotopic ossification at 6 weeks following the index trauma, specimens reveal immature undifferentiated tissues centrally with mature lamellar bone peripherally, known as the zonal phenomenon. TREATMENTSection 7 of 12
Medical therapyTraumatic heterotopic ossification can be treated in a number of ways. In the case of iatrogenic surgical trauma, prevention of the formation of heterotopic ossification should be considered the index treatment. A number of risk factors can be considered important in the pathogenesis of types of acquired heterotopic ossification:
Furthermore, patients who have conditions such as diffuse idiopathic skeletal hyperostosis, Paget disease, a preexisting hip fusion, posttraumatic arthrosis, hypertrophic osteoarthritis, or ankylosing spondylitis may be more likely to develop heterotopic ossification as a complication of total hip arthroplasty. Children with cerebral palsy who undergo hip soft-tissue releases or spinal surgery are thought to have an increased risk of developing heterotopic ossification. Risk factors that are related to surgical technique and are, therefore, potentially modifiable are as follows:
Some case series have shown that factors such as the lateral approach to the hip, the use of cementless components, and the use of a trochanteric osteotomy may increase the risk of heterotopic ossification in total hip arthroplasty, but these factors for increased risk are by no means certain. A patient with heterotopic ossification following total hip arthroplasty is thought to have a 90-100% chance of developing it on the contralateral hip if this hip also undergoes total arthroplasty. Consequently, certain patients with preexisting risk factors could conceivably be regarded as high risk and be treated with a more intensive prophylaxis regimen than standard, although this may not be practical. Nevertheless, it would be prudent to minimize the risk of heterotopic ossification developing after arthroplasty by performing surgery whereby the exposure is meticulous, retraction is performed carefully and soft tissue is handled carefully, irrigation is adequate, devitalized tissue is excised, hemostasis isadequate, postoperative drains (when used) are not retained for longer than necessary, perioperative antibiotic prophylaxis is used, and postoperative anticoagulation (when used for deep vein thrombosis prophylaxis) is carefully controlled. Surgical therapyBecause removal of heterotopic ossification may involve substantial blood loss and excision may be incomplete and because the risks of recurrence are high, surgeons attempting surgical removal of heterotopic ossification need to be familiar with the relevant surgical approaches to the affected region and how to safely enlarge and extend the wounds. Follow-upFollowing procedures that may be complicated by heterotopic ossification, recommendations indicate that prophylaxis should be given in the form of nonsteroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, or aspirinlike drugs that act as nonspecific cyclooxygenase inhibitors. The duration of treatment is controversial. Some studies have shown that treatment should continue for 6 weeks after the procedure; others have suggested that it need only be continued for 20, 14, or 7 days after the procedure. Bisphosphonates are ineffective in the prophylaxis of heterotopic ossification. An alternative or possible adjunct to cyclooxygenase inhibition is the use of localized irradiation. However, clinical evidence suggests that localized irradiation is not better than indomethacin alone for heterotopic ossification prophylaxis following surgery of acetabular fractures. Some clinicians would advocate the use of adjuvant radiation therapy in the prophylaxis of heterotopic ossification in individuals considered to be at high risk (defined as a >50% chance) of developing this condition. The irradiation protocol is controversial. Radiation therapy may be effective if given up to 24 hours preoperatively or within 72 hours postoperatively. However, it is unclear whether an optimal time to apply the treatment dose exists within these differing schedules. Randomized trials have shown that single fractions are as effective as multifraction schedules. Debate exists regarding the irradiation dosage. Some studies indicate that 7 Gy may be more effective than 5.5 Gy as a single dose, but other studies recommend 8 Gy or 12 Gy doses as single fractions or multifraction regimens. The role of radiation therapy in heterotopic ossification prophylaxis is not fully defined, and because its logistic availability is limited, its usage will continue to be selective rather than widespread. Depending on where the range of movement in the joints is impaired following arthroplasty as a result of heterotopic ossification, outpatient rehabilitation physiotherapy and hydrotherapy may be useful. The nature of the physiotherapy used for treatment is controversial. Forceful manipulation can be detrimental because the trauma involved can increase the heterotopic ossification development. Physiotherapy that involves passive and active elements to maintain and increase the range of movement in the affected joints can be beneficial. COMPLICATIONSSection 8 of 12
Heterotopic ossification may cause pain and stiffness. In turn, joint stiffness may cause further contractures. In severe cases, joint ankylosis may result. Nerve entrapment across joints also may be a complication of heterotopic ossification. Rare cases of heterotopic ossification undergoing malignant sarcomatous change have been reported. Prophylaxis using NSAIDs may be complicated by the adverse effects of these drugs. Radiation therapy complications may also occur if this approach is used for prophylaxis. However, the exact incidence of these complications is not known. Researchers have not performed long-term follow-up studies to detect late complications. OUTCOME AND PROGNOSISSection 9 of 12
If heterotopic ossification is excised, improvements in functional range of movement can be expected, although 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. FUTURE AND CONTROVERSIESSection 10 of 12
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. 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. The usage of selective cyclooxygenase-2 inhibitors, with improved side-effect profiles, is likely to replace the use of nonselective agents. 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. MULTIMEDIASection 11 of 12
REFERENCESSection 12 of 12
Traumatic Heterotopic Ossification excerpt Article Last Updated: Nov 17, 2006 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
