eMedicine Specialties > Radiology > Musculoskeletal

Heterotopic Ossification

Author: Daniel S Moore, MD, Department of Radiology, Assistant Professor, University of Texas Southwestern Medical Center at Dallas
Coauthor(s): Gina Cho, MD, Assistant Professor, Department of Radiology, Parkland Hospital, University of Texas Southwestern Medical Center
Contributor Information and Disclosures

Updated: Nov 6, 2007

Introduction

Background

Heterotopic ossification (HO) is the abnormal formation of true bone within extraskeletal soft tissues. Classically, many diseases sharing this common feature were lumped into the category myositis ossificans; however, the term has fallen into disfavor because primary muscle inflammation is not a necessary precursor for such ossification and the ossification does not always occur in muscle tissue (frequently showing a predilection instead for fascia, tendons, and other mesenchymal soft tissues). The term heterotopic ossification has largely replaced myositis ossificans in the literature.

Traditionally, various forms of HO have been classified according to the clinical setting and location of the lesions, as well as according to whether the lesions are progressive or isolated in occurrence. The varieties of HO are as follows:

  • Myositis ossificans traumatica - HO occurring after recalled trauma, such as blunt injury, surgery, or burns
  • Nontraumatic myositis ossificans - HO that occurs when no inciting trauma can be identified
  • Panniculitis ossificans - HO confined to subcutaneous fat
  • Rider's bones - HO found in the adductor muscles
  • Shooter's bones - HO located in the deltoid muscle

A strong association exists between HO and spinal cord injury, with lesions occurring at multiple sites and showing a strong propensity to recur. Similarly, periarticular HO is seen in patients with traumatic brain injury, with the extent and functional severity of the HO directly related to the severity of the intracranial injury. (See also the eMedicine articles Heterotopic Ossification [in the Physical Medicine and Rehabilitation section], Traumatic Heterotopic Ossification, Posttraumatic Heterotopic Ossification, and Heterotopic Ossification in Spinal Cord Injury.)

Many other causes of neurologic compromise, including tetanus, poliomyelitis, Guillain-Barré syndrome, and prolonged pharmacologic paralysis during mechanical ventilation, also have been associated with HO formation.

Fibrodysplasia ossificans progressiva (FOP), or Münchmeyer disease, is an autosomal dominant, severely disabling condition that results in progressive ossification of fascial planes, muscles, tendons, and ligaments. (See also the eMedicine article Myositis Ossificans.) Congenital malformation of the great toes also is associated with FOP. HO is a feature of several other diseases as well, including Albright hereditary osteodystrophy, progressive osseous heteroplasia, and primary osteoma cutis, but these are beyond the scope of this article.

Pathophysiology

HO originates from osteoprogenitor stem cells lying dormant within the affected soft tissues.1 With the proper stimulus, the stem cells differentiate into osteoblasts and begin the process of osteoid formation, eventually leading to mature heterotopic bone. A variety of bone morphogenetic proteins (BMPs) can stimulate HO when experimentally deposited into soft tissues, suggesting that BMPs play a role in the initiation of HO.2 A degree of neurologic control is implied but is not well understood.

Potentially causative mutations for FOP have been mapped to 2 sites, adding to the evidence of the BMPs' role in HO formation. The first site lies on the long arm of chromosome 17, in the region of the noggin gene (NOG). The noggin protein inhibits BMPs. The second genetic location is on the long arm of chromosome 4, in the region of a known BMP-signaling pathway gene. Bone morphogenetic protein 4 is overproduced in patients with FOP.

The typical histologic evolution of HO following trauma begins with spindle cell proliferation within the first week of the traumatic event. Primitive osteoid develops at the periphery of the lesion within 7-10 days. Primitive cartilage and woven bone can be seen in the second week, with trabecular bone forming at 2-5 weeks after the inciting trauma. After approximately 6 weeks, a zonal phenomenon characterized by immature, undifferentiated, central tissues and mature, peripherally located lamellar bone can be observed.

Frequency

International

Risk factors for HO include the presence of other bone-forming disorders, such as diffuse idiopathic skeletal hyperostosis, ankylosing spondylitis, and Paget disease. A personal history of previous HO also increases the risk of future occurrences. HO complicates 8-71% of total hip arthroplasty procedures, with the risk approaching 100% if the patient has had HO in a previous total arthroplasty site. Of patients with neurologic deficits, 20-30% develop HO, with as many as 50% of patients with spinal cord injury affected in some studies.

Mortality/Morbidity

The clinical impact of HO depends on the clinical setting and extent of the disease. A single lesion caused by trauma usually stabilizes and may regress; resulting symptoms depend on the location and size of the lesion. HO related to spinal cord injury or traumatic brain injury tends not to regress and may cause pain and decreased range of motion in affected joints; in such cases, the condition occasionally results in complete ankylosis and severe disability.3  Among patients with neurologic deficits, 8-10% have severe functional limitations resulting directly from HO. The extent of involvement is correlated positively with poorer outcome in rehabilitation patients recovering from traumatic brain injury. In patients with spinal cord injuries, large foci of HO can lead to skin breakdown and the inability to sit upright. Malignant degeneration to osteosarcoma has been reported but is extremely rare.

In FOP, the number and extent of lesions progress inexorably, with a consequent loss of normal limb and spinal function. Death may occur from recurrent respiratory infections resulting from chest wall restriction.

Race

Race does not appear to be a strong predisposing factor for HO in the setting of injury of the spinal cord, a site for which data are available. FOP might be expected to have racial or ethnic predilections because of its heritable nature; however, most cases are sporadic in nature because frequently patients who are affected do not have children.

Sex

Male patients with spinal cord injury are twice as likely to develop HO as are female patients.4 No strong sex predilection exists in FOP.

Age

Isolated HO can occur at any age but is rare in very young children. Posttraumatic HO is, not surprisingly, most common in young, athletic persons. In some studies, HO has been found to more frequently affect young patients (20-30 y) with spinal cord injury. Other studies have found no correlation between age and HO formation. In contrast, FOP tends to manifest in patients by age 5 years, causing severe restriction of upper extremity movement in most patients by age 15 years.

Anatomy

Posttraumatic HO can be found at any site. The most common postsurgical site is the hip, following total hip arthroplasty. The hip is also the most common site of HO occurrence in patients with traumatic brain injury or spinal cord injury. The next most common sites of involvement in patients with traumatic brain injury are the shoulders and elbows, with the knees rarely being affected. In contrast, knees frequently are involved in patients with spinal cord injury.

In FOP, involvement typically progresses from the axial to the appendicular skeleton, from cranial to caudal, and from proximal to distal. The disease typically spares the tongue, extraocular muscles, and diaphragm, as well as the cardiac and smooth muscles.

Presentation

Following trauma, HO often begins as a painful, palpable mass that gradually becomes nontender and smaller, as well as firmer to palpation. In spinal cord injury, patients frequently complain of lower extremity pain and swelling without antecedent trauma.

Some FOP lesions follow a specific traumatic event that the patient clearly remembers, but more often they are spontaneous, with the patient being unable to recall the occurrence of any recent trauma. Swelling, warmth, erythema, and pain are initially present. Over a period of weeks, the pain and swelling improve and may resolve completely. Alternatively, a hard, nontender, ossified lesion may arise approximately 6-12 weeks after the onset of symptoms at the site.

Differentiating early HO from lower extremity deep venous thrombosis (DVT) presents a particularly difficult diagnostic dilemma. The 2 conditions can present with the same symptoms of lower extremity pain, swelling, and erythema. Both occur more frequently in similar patient populations, namely, patients with spinal cord and traumatic brain injuries. In addition, HO and DVT have been positively associated, perhaps because the mass effect and local inflammation of HO encourage adjacent thrombus formation by causing venous compression and phlebitis.

Preferred Examination

Radiography is the preferred method of initial assessment for virtually all musculoskeletal conditions, including HO. Given their relatively low expense, radiographs should be obtained first (even if other imaging modalities are planned) in order to assess the extent of known HO.

Bone scanning is the method of choice for earliest detection and, once the diagnosis is established, for assessing the maturity of a known lesion.

Ultrasonography may have a role as a screening tool in the hip region after spinal cord injury; ultrasonograms may be obtained during a DVT screening examination.

Limitations of Techniques

Radiographs cannot detect the mineralization of HO during the first 1-2 weeks after the inciting trauma or the onset of symptoms. However, radiographs are recommended in all patients with suggested HO to assess underlying bone pathology and exclude other pathology.

Neither radiography nor computed tomography (CT) scanning should be performed in the pelvic region during pregnancy because of radiation exposure to the fetus, unless the risks of radiation exposure are outweighed by the need for a timely diagnosis. Nuclear medicine bone scanning also involves exposure of the fetus to radiation, regardless of the anatomic site being imaged, and should, if possible, be postponed until after delivery.

Ultrasonography is an operator-dependent modality. Proper evaluation of soft-tissue masses, including HO, requires considerable training and experience, available at some centers in the United States and, more commonly, in Europe. Radiologists who are less familiar with musculoskeletal ultrasonographic images may be more comfortable using CT scanning or nuclear medicine modalities to make the diagnosis of early HO.

Differential Diagnoses

Deep Venous Thrombosis, Lower Extremity
Osteomyelitis, Chronic
Osteosarcoma, Variants

Other Problems to Be Considered

Cellulitis
Diabetic muscle infarct
Hematoma
Hydroxyapatite deposition disease
Pyomyositis
Tumoral calcinosis

More on Heterotopic Ossification

Overview: Heterotopic Ossification
Imaging: Heterotopic Ossification
Follow-up: Heterotopic Ossification
Multimedia: Heterotopic Ossification
References
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Further Reading

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Keywords

ectopic ossification, heterotopic bone formation, myositis ossificans, ossifying fibromyopathy, panniculitis ossificans, para-articular ossification, paraosteoarthropathy, periarticular new bone formation, HO

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Contributor Information and Disclosures

Author

Daniel S Moore, MD, Department of Radiology, Assistant Professor, University of Texas Southwestern Medical Center at Dallas
Daniel S Moore, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Radiology, Association of University Radiologists, Radiological Society of North America, and Society of Skeletal Radiology
Disclosure: Nothing to disclose.

Coauthor(s)

Gina Cho, MD, Assistant Professor, Department of Radiology, Parkland Hospital, University of Texas Southwestern Medical Center
Gina Cho, MD is a member of the following medical societies: Alpha Omega Alpha, American Roentgen Ray Society, and Radiological Society of North America
Disclosure: Nothing to disclose.

Medical Editor

Giuseppe Guglielmi, MD, Associate Professor of Radiology, Department of Radiology, Scientific Institute Hospital
Disclosure: Nothing to disclose.

Pharmacy Editor

Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.

Managing Editor

William R Reinus, MD, MBA, FACR, Professor of Radiology, Temple University; Chief of Musculoskeletal and Trauma Radiology, Vice Chair, Department of Radiology, Temple University Hospital
William R Reinus, MD, MBA, FACR is a member of the following medical societies: American College of Physician Executives, American College of Radiology, American Roentgen Ray Society, Missouri State Medical Association, and Radiological Society of North America
Disclosure: Nothing to disclose.

CME Editor

Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.

Chief Editor

Felix S Chew, MD, MBA, EdM, Professor, Department of Radiology, Vice Chairman for Radiology Informatics, Section Head of Musculoskeletal Radiology, University of Washington
Felix S Chew, MD, MBA, EdM is a member of the following medical societies: American Roentgen Ray Society, Association of University Radiologists, and Radiological Society of North America
Disclosure: Nothing to disclose.

 
 
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