eMedicine Specialties > Physical Medicine and Rehabilitation > Traumatic Brain Injury

Posttraumatic Heterotopic Ossification: Differential Diagnoses & Workup

Author: Auri Bruno-Petrina, MD, PhD, Clinical Trainee, Pemberton Marine Medical Clinic, N Vancouver
Contributor Information and Disclosures

Updated: Jul 28, 2008

Differential Diagnoses

Other Problems to Be Considered

The differential diagnosis for heterotopic ossification (HO) in patients with soft-tissue swelling or loss of ROM includes thrombophlebitis, cellulites, septic arthritis, hematoma, fracture, or local trauma. The presence of fever due to HO may mimic deep venous thrombosis in presentation or osteomyelitis from hematogenous or contiguous spread.

FOP, a rare, genetic, autosomal dominant disease characterized by episodes of permanent HO of soft tissues, occurs worldwide without race, ethnic, or geographic predilection. No effective treatment is available, and soft-tissue trauma (eg, biopsies, surgical procedures, intramuscular injections, mandibular blocks for dental procedures), as well as viral illnesses, are likely to induce episodes of rapidly progressive HO, with a resultant permanent loss of motion in the affected area. Accurate diagnoses can be made based on the clinical findings of tumorlike swellings on the head, neck, back, or shoulders and characteristic short great toes with hallux valguslike malformations and missing interphalangeal joints.

For the nonfunctional shoulder, 70 º of abduction and 45 º of external rotation are usually sufficient to allow access to the axilla for washing and sufficient ROM for dressing. HO, typically inferomedial, does not interfere with ROM; restriction of shoulder motion is more likely attributable to other soft-tissue tightness. If present at the shoulder, HO is likely to be present at other joints, such as the elbow, hips, or knees; in these locations, HO usually causes a considerable number of clinical problems.

Workup

Laboratory Studies

  • Progressive loss of joint mobility and markers of increased osteoblastic activity, such as an elevated fractionated alkaline phosphatase level, warrant a comprehensive musculoskeletal examination with a 3-phase bone scan and radiographs to confirm the presence, distribution, and extent of heterotopic ossification (HO).1,2,3
  • The diagnosis of HO following brain injury typically is made by the clinical examination and by assessing for elevations in alkaline phosphatase. Early increases in alkaline phosphatase may be difficult to interpret, because the level rises with other causes, such as fractures or hepatotoxicity. The level of alkaline phosphatase has been reported to parallel the activity of ossification. It was found that when ossification stopped, the level returned to normal. Alkaline phosphatase fractionation studies reportedly can distinguish among different reasons for electrical levels.
  • Osteocalcin, another marker of osteoblastic activity, does not appear to be useful in the early detection of HO or in the assessment of its maturity. The erythrocyte sedimentation rate is too nonspecific to be of much help in the diagnosis of HO, but an elevated level associated with other clinical features suggests the need for further evaluation.

Imaging Studies

  • Heterotopic ossification (HO) typically cannot be seen on plain radiographs until several weeks after clinical manifestations (including pain, swelling, erythema, restricted ROM) become evident.
  • Radiographs may not show abnormalities during the acute phase of erythema and swelling. Later radiographs (1-2 weeks after onset) often show only soft-tissue swelling. Radiographs show immature ossification and then the appearance of mature bone. HO may take 8-14 months to reach maturity. Plain radiographs may not show evidence of HO until 4-5 weeks after injury.
  • Because of the limitations of plain radiography, radionuclide bone scanning is the preferred diagnostic test for earlier detection.4
  • On anteroposterior radiography, HO is usually located inferior and medial to the humeral head.
  • Excision may be undertaken to improve passive shoulder functions. Computed tomography (CT) scans of the shoulder (cross sections) and 3-dimensional reconstruction assist with preoperative planning. Radiographic assessment of joints with HO may be severely limited by difficulties in positioning the patient for the necessary view.

Other Tests

  • Many clinicians rely on triple-phase bone scanning technology for early detection of heterotopic ossification (HO). Triple-phase technetium-99m (99m Tc) bone scanning detects early increases in vascularity and is a reliable indicator in making a diagnosis.1 The first and second phases of the triple-phase bone scan show increased uptake. Areas demonstrating increased blood flow and soft-tissue concentration of the tracer on early imaging (blood flow phase) correlate with sites of subsequent HO development. The optimal timing of the imaging for accurate assessment of the presence of ectopic bone has not been established, but 3 weeks or more following the injury should be sufficient for early detection.

Procedures

  • Various authors who have reviewed the association between the human leukocyte antigen (HLA) system and heterotopic ossification (HO) have suggested that a genetic predisposition to an associated systemic factor exists; thus, an antigenic marker should be available to mark susceptible patients. Others have found no evidence of any association between the HLA system and HO. An association between HLA-B 18 and patients with neurologic disorders, as well as with patients who develop HO, has been described. However, 75% of patients with HO lack this marker.

Histologic Findings

Histologic examination demonstrates that tissue developed through heterotopic ossification (HO) is composed of true osseous tissue rather than of calcified soft tissue. Heterotopic bone is metabolically active and exhibits approximately triple the normal rate of bone formation and double the normal number of osteoclasts.

More on Posttraumatic Heterotopic Ossification

Overview: Posttraumatic Heterotopic Ossification
Differential Diagnoses & Workup: Posttraumatic Heterotopic Ossification
Treatment & Medication: Posttraumatic Heterotopic Ossification
Follow-up: Posttraumatic Heterotopic Ossification
Multimedia: Posttraumatic Heterotopic Ossification
References
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Further Reading

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Keywords

posttraumatic heterotopic ossification, heterotopic calcification, heterotopic ossification, HO, posttraumatic brain injury heterotopic ossification, traumatic brain injury, TBI, post-TBI heterotopic ossification, etidronate disodium, EHDP

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Contributor Information and Disclosures

Author

Auri Bruno-Petrina, MD, PhD, Clinical Trainee, Pemberton Marine Medical Clinic, N Vancouver
Auri Bruno-Petrina, MD, PhD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, Canadian Association of Physical Medicine and Rehabilitation, College of Physicians and Surgeons of British Columbia, and International Society of Physical and Rehabilitation Medicine
Disclosure: Nothing to disclose.

Medical Editor

Robert L Sheridan, MD, Assistant Chief of Staff, Chief of Burn Surgery, Shriners Burns Hospital; Associate Professor of Surgery, Department of Surgery, Division of Trauma and Burns, Massachusetts General Hospital and Harvard Medical School
Robert L Sheridan, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Surgery of Trauma, American Burn Association, and American College of Surgeons
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Patrick M Foye, MD, FAAPMR, FAAEM, Associate Professor of Physical Medicine and Rehabilitation, Co-Director of Musculoskeletal Fellowship, Co-Director of Back Pain Clinic, Director of Coccyx Pain (Tailbone Pain, Coccydynia) Service, University of Medicine and Dentistry of New Jersey, New Jersey Medical School
Patrick M Foye, MD, FAAPMR, FAAEM is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, Association of Academic Physiatrists, and International Spine Intervention Society
Disclosure: Nothing to disclose.

CME Editor

Kelly L Allen, MD, Consulting Staff, Department of Physical Medicine and Rehabilitation, Lourdes Regional Rehabilitation Center, Our Lady of Lourdes Medical Center
Disclosure: Nothing to disclose.

Chief Editor

Denise I Campagnolo, MD, MS, Director of Multiple Sclerosis Clinical Research and Staff Physiatrist, Barrow Neurology Clinics, St. Joseph's Hospital and Medical Center; Investigator for Barrow Neurology Clinics; Director, NARCOMS Project for Consort
Denise I Campagnolo, MD, MS is a member of the following medical societies: Alpha Omega Alpha, American Association of Neuromuscular and Electrodiagnostic Medicine, American Paraplegia Society, Association of Academic Physiatrists, and Consortium of Multiple Sclerosis Centers
Disclosure: Teva Neuroscience Honoraria Speaking and teaching; Serono-Pfizer Honoraria Speaking and teaching

 
 
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