eMedicine Specialties > Physical Medicine and Rehabilitation > Traumatic Brain Injury

Posttraumatic Heterotopic Ossification

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

Updated: Jul 28, 2008

Introduction

Background

In 1918, Dejerine and Ceillier first described heterotopic ossification (HO) in paraplegic patients injured in World War I, referring to the process as paraosteoarthropathy. HO has been defined as the formation of mature lamellar bone in soft tissues. The process involves true osteoblastic activity and bone formation. HO has been reported in cases of brain injury, spinal cord injury, stroke, poliomyelitis, myelodysplasia, tabes dorsalis, carbon monoxide poisoning, spinal cord tumors, syringomyelia, tetanus, and multiple sclerosis. This condition also has been reported after burns and total hip replacement/joint arthroplasty.

Several terms have been used to describe the condition, including heterotopic ossification, ectopic ossification, and myositis ossificans. HO usually involves the large joints of the body (eg, hips, elbows, shoulders, knees). Excessive bone formation may result in significant disability by severely limiting the range of motion (ROM) of these joints (see Image 1).

The following 3 categories of HO have been described:

  • Myositis ossificans progressiva - This is a rare metabolic bone disease in children with progressive metamorphosis of skeletal muscle to bone; it is characterized by an autosomal dominant pattern of genetic transmission.
  • Myositis ossificans circumscripta without trauma - Also referred to as neurogenic HO, this is a localized soft-tissue ossification occurring after neurologic injury or burns.
  • Traumatic myositis ossificans - This condition occurs from direct injury to the muscles. Fibrous, cartilaginous, and osseous tissues near bone are affected; the muscle may not be involved.

Related eMedicine topics:
Heterotopic Ossification [Physical Medicine and Rehabilitation]
Heterotopic Ossification [Radiology]
Heterotopic Ossification in Spinal Cord Injury
Myositis Ossificans
Traumatic Heterotopic Ossification

Related Medscape topic:
Resource Center Joint Disorders

Pathophysiology

The specific cause and pathophysiology of heterotopic ossification (HO) remain uncertain, but the condition appears to involve the inappropriate differentiation of mesenchymal cells into osteoblastic stem cells in response to still-unidentified inducing agents.

HO may be due to an interaction between local factors (eg, the pool of available calcium in adjacent skeleton, soft-tissue edema, vascular stasis tissue hypoxia, mesenchymal cells with osteoblastic activity) and an unknown systemic factor or factors. The basic defect in HO is the inappropriate differentiation of fibroblasts into bone-forming cells. Early edema of connective tissue proceeds to tissue with foci of calcification and then to maturation of calcification and ossification.

Frequency

United States

The reported incidence of heterotopic ossification (HO) varies. In cases of severe trauma or insult to the central nervous system (CNS), 10-20% of patients develop HO, and the condition has been observed in 20% of patients with severe brain injury. The incidence is higher in patients who undergo open reduction and internal fixation of a fracture. With an elbow fracture, dislocation, or fracture-dislocation, the incidence of traumatic HO at the elbow approaches 90%. Traumatic HO of the elbow occurs in 20% of forearm fractures. Fifty-five percent of patients with hip fractures develop HO. The incidence increases to 83% if open reduction and internal fixation are performed. The incidence is similar in the upper and lower extremities.

An association has been cited between spasticity and HO. The incidence is higher in a spastic extremity; 84% of patients with HO had spasticity, and 54% of patients with HO had no spasticity. HO is seen in the elbow in 4% of patients with traumatic brain injury (TBI); however, if fracture or dislocation is associated with brain injury, the incidence of HO rises to 89%.

Related eMedicine topics:
Classification and Complications of Traumatic Brain Injury
Neurointensive Care for Traumatic Brain Injury in Children
Traumatic Brain Injury: Definition, Epidemiology, Pathophysiology

International

Studies from Europe and Japan have shown the incidence of HO to range between 11% and 76%, depending on the population studied and on the method of detection.

Mortality/Morbidity

Only 10-20% of all heterotopic ossification (HO) patients have functionally significant deficits.

Race

No race predilection exists for heterotopic ossification.

Sex

The development of heterotopic ossification is independent of the patient's sex.

Age

An increased incidence of heterotopic ossification (HO) has been found in persons over age 30 years. The incidence of HO in children appears to be lower than that in adults (8-22.5%).

Clinical

History

The earliest sign of heterotopic ossification (HO) often is decreased joint ROM. Other findings include swelling, erythema, heat, pain with ROM testing, and contracture formation, but the condition may be occult. Fever also may be present. Patients with HO can experience pain, increased spasticity, vascular and nerve compression, and lymphedema.

Physical

In heterotopic ossification (HO), ectopic bone usually forms around major joints (eg, elbows, shoulders, hips, knees) following brain injury, as well as over long-bone fractures. The proximal interphalangeal joints of the hand, wrist, and spine also may be affected. Local pain and a palpable mass may be noted in the periarticular region, usually presenting 1-3 months after the injury, but the onset of HO also has been reported at 1-7 months following severe brain injury.

HO can mimic thrombophlebitis, with pain, swelling, erythema, and induration of the affected area. If HO affects a joint, a decrease in ROM often is observed. Major, long-term disability from untreated HO can include limited ROM or even joint ankylosis.

In patients with a history of fractures, spasticity, and low-level responsiveness, the detection of restricted motion should suggest HO. Excessive bone formation may result in significant disability by severely limiting the ROM of a joint.

Complete elbow ankylosis without severe injury of the CNS has been described.

Causes

Patients with brain injuries are at greater risk for developing heterotopic ossification (HO) if they have significant spasticity or increased muscle tone in the involved extremity, unconsciousness lasting longer than 2 weeks, long-bone or associated fractures, and decreased ROM. Therefore, the risk of development of HO in a patient with brain injury increases as the severity of injury, length of immobilization, and duration of coma increase.

In patients with fibrodysplasia ossificans progressiva (FOP) (often misdiagnosed as cancer), any soft-tissue trauma (eg, biopsies, surgical procedures, intramuscular injections, mandibular blocks for dental procedures) and viral illnesses are likely to induce episodes of rapidly progressive HO, with a resultant permanent loss of motion in the affected area.

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
[ CLOSE WINDOW ]

References

  1. Orzel JA, Rudd TG. Heterotopic bone formation: clinical, laboratory, and imaging correlation. J Nucl Med. Feb 1985;26(2):125-32. [Medline].

  2. Freed JH, Hahn H, Menter R. The use of the three-phase bone scan in the early diagnosis of heterotopic ossification (HO) and in the evaluation of Didronel therapy. Paraplegia. Aug 1982;20(4):208-16. [Medline].

  3. Svircev JN, Wallbom AS. False-negative triple-phase bone scans in spinal cord injury to detect clinically suspect heterotopic ossification: a case series. J Spinal Cord Med. 2008;31(2):194-6. [Medline].

  4. Tanaka T, Rossier AB, Hussey RW. Quantitative assessment of para-osteo-arthropathy and its maturation on serial radionuclide bone images. Radiology. Apr 1977;123(1):217-21. [Medline].

  5. Garland DE, Razza BE, Waters RL. Forceful joint manipulation in head-injured adults with heterotopic ossification. Clin Orthop Relat Res. Sep 1982;133-8. [Medline].

  6. Hastings H 2nd, Graham TJ. The classification and treatment of heterotopic ossification about the elbow and forearm. Hand Clin. Aug 1994;10(3):417-37. [Medline].

  7. Ring D, Jupiter JB. Operative release of complete ankylosis of the elbow due to heterotopic bone in patients without severe injury of the central nervous system. J Bone Joint Surg Am. May 2003;85-A(5):849-57. [Medline].

  8. Fingerman G, Krengel W, Lowell JD, et al. Role of Diphosphonate EHDP in the Prevention of Heterotopic Ossification After Total Hip Arthroplasty: Preliminary Report. Proceedings of the Fifth Open Scientific Meeting of the Hip Society, St Louis, Mo. 222-34.

  9. Coventry MB, Scanlon PW. The use of radiation to discourage ectopic bone. A nine-year study in surgery about the hip. J Bone Joint Surg Am. Feb 1981;63(2):201-8. [Medline].

  10. Esenwein SA, Sell S, Herr G, et al. Superior efficacy in suppression of heterotopic bone formation using fractionated irradiation of 5 x 2 Gy compared to a single dose of 7 Gy. An experimental study in rats. Acta Orthop Belg. Apr 2003;69(2):119-26. [Medline].

  11. Strauss JB, Chen SS, Shah AP, et al. Cost of radiotherapy versus NSAID administration for prevention of heterotopic ossification after total hip arthroplasty. Int J Radiat Oncol Biol Phys. Jan 28 2008;[Medline].

  12. Spielman G, Gennarelli TA, Rogers CR. Disodium etidronate: its role in preventing heterotopic ossification in severe head injury. Arch Phys Med Rehabil. Nov 1983;64(11):539-42. [Medline].

  13. Stover SL, Hahn HR, Miller JM 3rd. Disodium etidronate in the prevention of heterotopic ossification following spinal cord injury (preliminary report). Paraplegia. Aug 1976;14(2):146-56. [Medline].

  14. Beck A, Salem K, Krischak G, et al. Nonsteroidal anti-inflammatory drugs (NSAIDs) in the perioperative phase in traumatology and orthopedics effects on bone healing. Oper Orthop Traumatol. Dec 2005;17(6):569-78. [Medline].

  15. Fransen M. Preventing chronic ectopic bone-related pain and disability after hip replacement surgery with perioperative ibuprofen. A multicenter, randomized, double-blind, placebo-controlled trial (HIPAID). Control Clin Trials. Apr 2004;25(2):223-33. [Medline].

  16. Ritter MA, Gioe TJ. The effect of indomethacin on para-articular ectopic ossification following total hip arthroplasty. Clin Orthop Relat Res. Jul 1982;113-7. [Medline].

  17. Ritter MA, Sieber JM. Prophylactic indomethacin for the prevention of heterotopic bone formation following total hip arthroplasty. Clin Orthop Relat Res. Jun 1985;217-25. [Medline].

  18. Tannenbaum H, Davis P, Russell AS, et al. An evidence-based approach to prescribing NSAIDs in musculoskeletal disease: a Canadian consensus. Canadian NSAID Consensus Participants. CMAJ. Jul 1 1996;155(1):77-88. [Medline]. [Full Text].

  19. Wheeler P, Batt ME. Do non-steroidal anti-inflammatory drugs adversely affect stress fracture healing? A short review. Br J Sports Med. 2005;2:65-9. [Medline]. [Full Text].

  20. Bek D, Beksaç B, Della Valle AG, et al. Aspirin decreases the prevalence and severity of heterotopic ossification after 1-stage bilateral total hip arthroplasty for osteoarthrosis. J Arthroplasty. Mar 27 2008;[Medline].

  21. Macfarlane RJ, Ng BH, Gamie Z, et al. Pharmacological treatment of heterotopic ossification following hip and acetabular surgery. Expert Opin Pharmacother. Apr 2008;9(5):767-86. [Medline].

  22. Flanagan SR, Kwasnica C, Brown AW, et al. Congenital and acquired brain injury. 2. Medical rehabilitation in acute and subacute settings. Arch Phys Med Rehabil. Mar 2008;89(3 Suppl 1):S9-14. [Medline].

  23. Abrams RA, Simmons BP, Brown RA, et al. Treatment of posttraumatic radioulnar synostosis with excision and low-dose radiation. J Hand Surg [Am]. Jul 1993;18(4):703-7. [Medline].

  24. Bontke CF, Boake C. Principles of brain injury rehabilitation. In: Braddom RL, ed. Physical Medicine and Rehabilitation. 2nd ed. Philadelphia, Pa: WB Saunders; 1999.

  25. Finlayson MAJ, Garner SH, eds. Brain Injury Rehabilitation: Clinical Considerations. Baltimore, Md: Williams & Wilkins; 1994.

  26. Buschbacher R. Heterotopic ossification: a review. Crit Rev Phys Med. 1992;4:199.

  27. Chestnut RM. Medical complications of the head injured patient. In: Cooper PR, ed. Head Injury. 3rd ed. Baltimore, Md: Williams & Wilkins; 1993.

  28. Chua KS, Kong KH. Acquired heterotopic ossification in the settings of cerebral anoxia and alternative therapy: two cases. Brain Inj. Jun 2003;17(6):535-44. [Medline].

  29. Cohly HH, Buckley RC, Pecunia R, et al. Heterotopic bone formation: presentation of an experimental rat model and a clinical case. Biomed Sci Instrum. 2003;39:446-53. [Medline].

  30. Colachis SC 3rd, Clinchot DM, Venesy D. Neurovascular complications of heterotopic ossification following spinal cord injury. Paraplegia. Jan 1993;31(1):51-7. [Medline].

  31. Cope R. Heterotopic ossification. South Med J. Sep 1990;83(9):1058-64. [Medline].

  32. Dejerine A, Ceillier A. Paraosteoarthropathies of paraplegic patients by spinal cord lesion. Clinical and roentgenographic study. Clin Orthop Relat Res. Feb 1991;3-12. [Medline].

  33. Djergaian RS. Management of musculoskeletal complications. In: Horn LJ, Zasler ND, eds. Medical Rehabilitation of Traumatic Brain Injury. Philadelphia, Pa: Hanley & Belfus; 1996.

  34. Fransen M, Neal B. Non-steroidal anti-inflammatory drugs for preventing heterotopic bone formation after hip arthroplasty. Cochrane Database Syst Rev. 2004;CD001160. [Medline].

  35. Freed MM. Traumatic and congenital lesions of the spinal cord. In: Kottke PS, Stillwell OK, Lehmann JP, eds. Krusen's Handbook of Physical Medicine and Rehabilitation. 3rd ed. Philadelphia, Pa: WB Saunders; 1982:643-73.

  36. Fujimori Y, Nakamura T, Ijiri S. Heterotopic bone formation induced by bone morphogenetic protein in mice with collagen-induced arthritis. Biochem Biophys Res Commun. Aug 14 1992;186(3):1362-7. [Medline].

  37. Garland DE. A clinical perspective on common forms of acquired heterotopic ossification. Clin Orthop Relat Res. Feb 1991;13-29. [Medline].

  38. Garland DE, Blum CE, Waters RL. Periarticular heterotopic ossification in head-injured adults. Incidence and location. J Bone Joint Surg Am. Oct 1980;62(7):1143-6. [Medline].

  39. Garland DE, Hanscom DA, Keenan MA. Resection of heterotopic ossification in the adult with head trauma. J Bone Joint Surg Am. Oct 1985;67(8):1261-9. [Medline].

  40. Garland DE, Orwin JF. Resection of heterotopic ossification in patients with spinal cord injuries. Clin Orthop Relat Res. May 1989;169-76. [Medline].

  41. Gean AD. Imaging of Head Trauma. New York, NY: Raven Press; 1994.

  42. Gennarelli TA. Cerebral concussion and diffuse brain injuries. In: Cooper PA, ed. Head Injury. Philadelphia, Pa: Williams & Wilkins; 1993:137-58.

  43. Gennarelli TA. Heterotopic ossification. Brain Inj. Apr-Jun 1988;2(2):175-8. [Medline].

  44. Glenn M, Rosenthal M. Rehabilitation following severe traumatic brain injury. Semin Neurol. 1985;5:233-46.

  45. Gonzales-Mas R. Reabilitacion del traumatizado craneoencefalico [in Spanish]. Revista Iberoamericana de Rehabilitacion Medica. 1995;48(16):1-11.

  46. Harder AT, An YH. The mechanisms of the inhibitory effects of nonsteroidal anti-inflammatory drugs on bone healing: a concise review. J Clin Pharmacol. Aug 2003;43(8):807-15. [Medline].

  47. Ippolito E, Formisano R, Caterini R, et al. Operative treatment of heterotopic hip ossification in patients with coma after brain injury. Clin Orthop Relat Res. Aug 1999;130-8. [Medline].

  48. Keenan MA, Haider T. The formation of heterotopic ossification after traumatic brain injury: a biopsy study with ultra-structural analysis. J Head Trauma Rehabil. 1996;11(4):8-22.

  49. Khan FA. Bilateral ankylosis of the hips following heterotopic ossification of the ilio-psoas in a child. Int Orthop. 1992;16(2):202-4. [Medline].

  50. Kitterman JA, Kantanie S, Rocke DM, et al. Iatrogenic harm caused by diagnostic errors in fibrodysplasia ossificans progressiva. Pediatrics. Nov 2005;116(5):e654-61. [Medline]. [Full Text].

  51. Krum SD, Miller F. Heterotopic ossification after hip and spine surgery in children with cerebral palsy. J Pediatr Orthop. Nov-Dec 1993;13(6):739-43. [Medline].

  52. Lee M, Alexander MA, Miller F. Postoperative heterotopic ossification in the child with cerebral palsy: three case reports. Arch Phys Med Rehabil. Mar 1992;73(3):289-92. [Medline].

  53. Mayer NH, Esquenazi A, Keenan MA. Analysis and management of spasticity, contracture, and impaired motor control. In: Horn LJ, Zasler NE, eds. Medical Rehabilitation of Traumatic Brain Injury. Philadelphia, Pa: Hanley & Belfus; 1996.

  54. Mital MA, Garber JE, Stinson JT. Ectopic bone formation in children and adolescents with head injuries: its management. J Pediatr Orthop. Jan-Feb 1987;7(1):83-90. [Medline].

  55. Mysiw WJ, Fugate LP, Clinchot DM. Assessment, early rehabilitation and tertiary prevention. In: Horn LJ, Zasler ND, eds. Medical Rehabilitation of Traumatic Brain Injury. Philadelphia, Pa: Hanley & Belfus; 1996.

  56. Naraghi FF, DeCoster TA, Moneim MS, et al. Heterotopic ossification. Orthopedics. Feb 1996;19(2):145-51. [Medline].

  57. Neal BC, Rodgers A, Clark T, et al. A systematic survey of 13 randomized trials of non-steroidal anti-inflammatory drugs for the prevention of heterotopic bone formation after major hip surgery. Acta Orthop Scand. Apr 2000;71(2):122-8. [Medline]. [Full Text].

  58. Payne LZ, DeLuca PA. Heterotopic ossification after rhizotomy and femoral osteotomy. J Pediatr Orthop. Nov-Dec 1993;13(6):733-8. [Medline].

  59. Pennig D, Mader K, Gausepohl T. [Posttraumatic elbow stiffness: planning and technical aspects of arthrolysis]. Zentralbl Chir. Feb 2005;130(1):32-9. [Medline].

  60. Reed MH, McGinn G, Black GB. Heterotopic ossification in children after iliopsoas release. Can Assoc Radiol J. Jun 1992;43(3):195-8. [Medline].

  61. Rogers RO. Program idea: heterotopic calcification in severe head injury: a preventive program. Brain Inj. 1988;2:169.

  62. Ruff RM, Marshall LF, Crouch J. Predictors of outcome following severe head trauma: follow-up data from the Traumatic Coma Data Bank. Brain Inj. Mar-Apr 1993;7(2):101-11. [Medline].

  63. Sazbon L, Najenson T, Tartakovsky M. Widespread periarticular new-bone formation in long-term comatose patients. J Bone Joint Surg Br. Feb 1981;63-B(1):120-5. [Medline].

  64. Sorenson SB, Kraus JF. Occurrence, severity and outcomes of brain injury. Bone Joint Surg Br. 1981;63:120.

  65. Stover SL, Niemann KM, Tulloss JR. Experience with surgical resection of heterotopic bone in spinal cord injury patients. Clin Orthop Relat Res. Feb 1991;71-7. [Medline].

  66. Trentz OA, Handschin AE, Bestmann L, et al. Influence of brain injury on early posttraumatic bone metabolism. Crit Care Med. Feb 2005;33(2):399-406. [Medline].

  67. Whyte J, Hart T, Laborde A, et al. Rehabilitation of the patient with traumatic brain injury. In: Delisa JA, Gans BM, eds. Rehabilitation Medicine: Principles and Practice. 3rd ed. Philadelphia, Pa: Lippincott-Raven; 1998.

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

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

[ CLOSE WINDOW ]

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

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.