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.
Heterotopic ossification is displayed in the images below.
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.
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. 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.
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. [1, 2]
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.
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.
Failure to distinguish heterotopic ossification from an osteoblastic neoplasm, such as osteosarcoma, is a pitfall.
Aggressive imaging findings may lead to a percutaneous biopsy, which can yield a sample with high cellular activity and new bone formation; these characteristics can potentially be confusing to the pathologist. An open biopsy may fare no better; it can exacerbate the severity of HO or, if the biopsy follows an early resection, cause a recurrence of the condition. Biopsy is contraindicated in patients with an established diagnosis of fibrodysplasia ossificans progressiva.
Another pitfall is the failure to use a conservative approach to follow-up radiologic imaging if developing HO is in the differential for a soft-tissue mass. Films can be obtained over a period of a few months at 2- to 4-week intervals to assess for the maturation of the osseous elements and increasing circumscription of the lesion (as opposed to the characteristics of an aggressive neoplasm's progression).
A soft tissue mass is the earliest radiographic finding of heterotopic ossification (HO), although a mass is often overlooked at sites such as the hip and thigh. Mineralization of the osteoid lesional content can be seen as early as 10-14 days after the inciting trauma. A peripheral zone of early mineralization is the most common pattern, although many lesions have a less organized appearance. Typically, HO associated with fibrodysplasia ossificans progressiva first mineralizes centrally. If untreated, mature cortical bone ultimately results.
To view radiographs of heterotopic ossification, see the images below.
Degree of confidence
Peripheral ossification of a soft tissue mass at the site of recent trauma is consistent with HO. Performing a biopsy to exclude a neoplasm should be avoided. Instead, delayed radiographs should be performed in 4 weeks to confirm maturation of the lesion into typical HO.
False positives can be caused by avulsion fracture fragments, osteochondral bodies within a distended joint capsule, nonosseous soft tissue calcification (which can resemble amorphous, early mineralization of woven bone), and osteosarcoma.
False negatives are common, most often occurring in lesions in which it is too early for mineralization to be seen radiographically or at sites that have been obscured by generous, overlying soft tissues or by normal bone. Sensitivity and specificity increase with time as lesions display more mature, dense ossification.
The earliest CT scan findings include a low-attenuation soft tissue mass or an enlarged muscle belly, occasionally with indistinct, adjacent soft-tissue planes (see the images below). [4, 5] Faint, immature bone mineralization becomes evident earlier than on radiographs, as lesions mature. With further maturation, lesions often demonstrate zonal mineralization with a mature peripheral cortex and may have central, fat-containing marrow elements. Abnormal, low-attenuation findings may persist in the soft tissues surrounding the mature cortex for months to years after the disease's onset. [6, 7, 8]
CT scans demonstrate high specificity for HO when the typical zonal pattern of peripheral mineralization is present.  Earlier in the course of HO evolution, when the lesion appears as an enhancing mass with disorganized or absent mineralization, findings are nonspecific. A repeat CT scan after several weeks of further maturation may help resolve the diagnostic dilemma.
Many masslike conditions, including the presence of an inflammatory mass or a soft-tissue neoplasm, can mimic the early appearance of HO.
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) is not routinely employed for the evaluation of heterotopic ossification (HO) once the diagnosis is established. [10, 11] Cases are most often encountered when MRI is required to assess a mass that has been detected clinically. HO may be seen incidentally in patients at risk, such as paraplegics, in whom it may be found while they are undergoing assessment for pelvic osteomyelitis. 
To view MRIs of heterotopic ossification, see the images below.
Early HO lesions demonstrate a heterogeneous, high T2 signal and a masslike enlargement of affected tissues.  A low-signal-intensity rim may be seen. Frequently, an extensive, ill-defined, surrounding, high T2 signal is noted. Intravenous gadolinium administration results in early, intense, heterogeneous enhancement of lesions.
Delayed imaging that takes place weeks to months after onset demonstrates a low-signal rim corresponding to maturing cortical bone on radiographs, with persistence of the heterogeneous, high T2 signal lesional content and extensive surrounding edema.
Several months after HO's onset, imaging characteristics reveal decreasing edema within and surrounding the lesion. High T1 and T2 signals that are isointense to fat develop centrally, probably representing marrow fat. Late lesions typically do not enhance.
Gadolinium-based contrast agents have been linked to the development of nephrogenic systemic fibrosis (NSF) or nephrogenic fibrosing dermopathy (NFD). The disease has occurred in patients with moderate to end-stage renal disease after being given a gadolinium-based contrast agent to enhance MRI or magnetic resonance angiography (MRA) scans.
NSF/NFD is a debilitating and sometimes fatal disease. Characteristics include red or dark patches on the skin; burning, itching, swelling, hardening, and tightening of the skin; yellow spots on the whites of the eyes; joint stiffness with trouble moving or straightening the arms, hands, legs, or feet; pain deep in the hip bones or ribs; and muscle weakness.
Degree of confidence
As on CT scans, early lesions have a very nonspecific appearance on magnetic resonance images.  With time, the development of a zonal pattern of maturation may suggest HO, although the appearance is often misleading. Correlation with conventional radiographs is strongly recommended to confirm the diagnosis.
On magnetic resonance images, as on CT scans, many masslike conditions, including infectious, inflammatory, and neoplastic disorders, can have an appearance similar to that of HO.
Ultrasonography is not generally used to assess heterotopic ossification once the diagnosis is established. However, because of the overlap of clinical presentation with deep venous thrombosis, combined with the widespread use of ultrasonography to screen for DVT, ultrasonographers can expect to encounter HO in the lower extremities of patients at risk. [14, 15] Some authors have proposed the use of ultrasonography as a simultaneous screening tool for HO and DVT in patients with spinal cord injury (see the image below).
Within a few hours of the onset of clinical symptoms, ultrasonograms demonstrate a chaotic disruption of the normal lamellar structure of skeletal muscle, which can be seen up to 10-14 days before radiographic evidence of HO appears. Later, still in the preradiographic phase, a zonal, masslike pattern develops that is peripherally echogenic and centrally hypoechoic. Once early mineralization becomes radiographically visible, ultrasonograms demonstrate sheets or irregular clumps of echogenic material with acoustic shadowing. Mature lesions have the echogenicity and dense shadowing of cortical bone.
Degree of confidence
As with HO findings on magnetic resonance images, those on ultrasonograms should be confirmed with radiographs and followed for the typical maturation pattern of HO.
Early in the disorganized, preradiographic phase, HO can have an appearance similar to that of a variety of posttraumatic, inflammatory, and neoplastic conditions.
A 3-phase, radionuclide bone scan using technetium-99m (99m Tc) methylene diphosphonate remains the criterion standard for detecting early heterotopic ossification. [16, 17] The examination consists of a radionuclide angiogram followed by a blood pool image over the suggestive site. A delayed image is obtained 2-3 hours later. (See the images below.)
Bone scans are typically positive more than 2 weeks before radiographic evidence of mineralization is seen, with some authors reporting positive findings on bone scan 4-6 weeks earlier than on radiographs. In very early lesions, only the first-pass or blood pool image findings may be abnormal, reflecting the hypervascularity of early heterotopic ossification. Soft tissue uptake in the third phase subsequently develops within 1 week of the appearance of first-pass and second-pass abnormalities. Soft tissue uptake is considered diagnostic of HO in the appropriate clinical setting.
Gallium-67 uptake is commonly demonstrated and may potentially be confused with infection in patients with spinal cord injuries.
Early on, heterotopic ossification lesions are hypervascular, with numerous fine vessels that lack the disordered characteristics of tumor neovascularity (eg, arteriovenous shunting or puddling).
Mature HO is usually avascular but may cause the extrinsic compression of adjacent vessels.