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Heterotopic Ossification

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Alibrahim F, McIntyre A, Faltynek P, Benton B, Mehta S, Loh E, Teasell RW (2018). Heterotopic Ossification Following Spinal Cord Injury. In Eng JJ, Teasell RW, Miller WC, Wolfe DL, Townson AF, Hsieh JTC, Connolly SJ, Loh E, Sproule S, McIntyre A, Querée M, editors. Spinal Cord Injury Rehabilitation Evidence. Version 7.0: p 1-24.


 

Key Points

  • Anti-inflammatory medications given early post-spinal cord injury reduces development of heterotopic ossification.
  • Warfarin may inhibit the development of heterotopic ossification post-spinal cord injury.
  • Alendronate does not prevent the development of heterotopic ossification and may cause contractures.
  • Etidronate may be effective for halting the progression of heterotopic ossification when administered early.
  • Pamidronate halts secondary progression of heterotopic ossification post-surgical excision.
  • Pulse low intensity electromagnetic field therapy is effective in preventing heterotopic ossification post spinal cord injury.
  • Radiotherapy can reduce the progression and recurrence of heterotopic ossification.
  • Surgical resection of heterotopic ossification can improve hip range of motion but it may recur in a large number of individuals.
  • Surgical resection and pamidronate treatment halts secondary heterotopic ossification progression.

 

Executive Summary
Heterotopic ossification (HO) is the formation of pathological bone in muscle or soft tissue (Shehab, Elgazzar & Collier, 2018). The incidence in individuals following a spinal cord injury (SCI) has been reported to vary greatly, ranging from 10% to 78% (Banovac 2001; van Kuijk et al. 2002, Ranganathan et al. 2015). HO occurs most frequently in the first two months after SCI, below the level of paralysis (Banovac et al. 2001) and most commonly forms in the hip but rarely the peripheral joints (Ranganathan et al. 2015). The mechanism underlying HO following spinal cord injury is not fully understood creating challenges in early diagnostic and therapeutic interventions.

What are the clinical symptoms of Heterotopic Ossification following injury?

Risk Factors for HO (Citak et al. 2012; Krauss et al. 2014)
• Complete neurological deficit
• Spasticity
• Pneumonia
• Thoracic trauma
• Tracheostomy
• Nicotine use
• Urinary tract infection
• Less comorbidities
• Hyper-coagulable states
• Deep vein thrombosis (DVT)
• Pulmonary embolism (PE)

Evaluation of preceding factors, in combination with early intervention and diagnosis, may reduce incidence of HO or improve a patient’s recovery post-operatively (Citak et al. 2012).

Clinical symptoms of HO being to appear 3-12 weeks post injury (Schuetz et al. (2005), and include: joint and muscle pain, parasthesias and tissue swelling in the involved region, accompanied by a mild fever (Thomas & Amstutz 1987; Orzel & Rudd 1985; Smith 1998; Shehab et al. 2002), while some SCI patients do not experience any pain.

How is Heterotopic Ossification diagnosed?
Triple phase bone scanning: More sensitive, but less specific than plain radiography in detecting early HO (Freed et al. 1982).
Plain Radiography: Can detect neurogenic HO 2-6 weeks after diagnosis using triple phase bone scan (Orzel et al. 1985; Freed et al. 1982).
Computed tomography (CT) or Magnetic Resonance Imaging (MRI): Better visualization of heterotopic bone (Amendola et al. 1983); useful when considering surgery.
Biochemical Markers: Used to evaluated elevations in alkaline phosphatase and creatine phosphokinase, however value has not been validated (Singh et al. 2003; Welch et al. 1973; Rossier et al. 1973).
Brooker Classification Scheme: Typically used to diagnose HO in the pelvic region using anteroposterior radiograph of the pelvis which classifies HO into one of five classes (Zychowicz 2013). Has been criticized by some clinicians, as it cannot be used to determine the potential drawbacks of surgery and gives pessimistic results of hip range of motion with some hips classified as III or IV despite no clinical ankylosis found.

What management options are there for Heterotopic Ossification?

Non-steroidal anti-inflammatory medications: Indomethacin and Rofecoxib have both been evaluated in the treatment of HO post SCI, however Rofecoxib is no longer available due to cardiovascular side effects (Banovac et al. 2001).
Anticoagulants: Warfarin may be useful in the prevention of HO post SCI (Buschbacher et al. 1992).
Bisphosphonates: Alendronate had no direct correlation for prevention of HO and may cause contractures (Ploumis et al. 2015). Etidronate was shown in several studies to halt the progression of HO (Garland et al. 1983; Banovac et al. 1993; Banovac et al. 1997; Stover et al. 1987). Pamidronate effectively halts secondary prevention of HO after surgical resection of heterotopic ossification (Schuetz et al. 2005).
Pulse Low Intensity Electromagnetic Field Therapy: Effective in preventing HO post-spinal cord injury (Durovic et al. 2009).
Radiation Therapy: Although the evidence is limited, studies show that radiotherapy reduces the progression of HO (Sautter-Bihl et al. 2000; Sautter-Bihl et al. 2001).
Surgical Resection: Can improve hip range of motion but recurrence and complications are of concern (Genet et al. 2011; Garland & Orwin 1989; Meiners et al. 1997).

GAPS IN THE EVIDENCE

• Mechanism of action of NSAIDs in preventing the occurrence of HO
• The role of NSAIDs once the patient starts to develop symptoms with or without radiographic evidence of HO
• Optimal criteria for decisions regarding excision