8.2 Heterotopic Ossification (HO)

Case Study (continued)

The physiotherapist who is working on mobility reports that the patient’s right hip is warm, swollen and painful; she is concerned about decreasing range of motion of that hip.

What would be in the differential diagnosis?

1.    Heterotopic ossification

2.    Fractured bone

3.    Rarely infected hip joint

8.2.1   Defining Heterotopic Ossification

What is heterotopic ossification? 

  1. Process whereby new bone forms within tissues where bone formation does not usually occur.
  • Heterotopic ossification (HO) is a process where new bone forms within tissues where bone formation does not usually occur29.
     
  • The incidence of HO in TBI patients has been reported as ranging from 11% to 77% but the disease only reaches clinical significance in 11-35% of this group 30-32.
     
  • Skeletal trauma, spasticity, immobilization, and prolonged coma greater than 2 weeks are considered to be at highest risk 33;34.
     
  • HO can potentially impede progress of patients towards their desired rehabilitation goals as it can restrict joint range of motion, thus restricting mobility or functional abilities.

8.2.2   Formation of Heterotopic Ossification Post-Head Injury

 Describe the pathophysiology of heterotopic bone formation post ABI.

  1. The pathophysiology of HO is not well understood. It is believed that there is a neurogenic factor contributing to HO, although this mechanism is not yet understood,
     
  2. Initial formation of osteoid.
     
  3. Progression to full calcification within weeks.
     
  4. Calcified osteoid remodels into well-organized trabecular bone over the ensuing months.
     
  5. The bony lesion has been found to have a high metabolic rate, with a rate of bone formation more than three times greater than that of normal bone and an osteoclastic density of more than twice the number of osteoclasts found in normal bone.
  • The pathophysiology of HO is not well understood.
     
  • It is believed that there is a neurogenic factor contributing to HO, although this mechanism is not yet understood 35;38;39.
     
  • Pape et al. 38 noted:
    • that mesenchymal stem cells can generate cartilage, bone, muscle, tendons, ligaments or fat 40and are thought to play a pivotal role in the development of HO;
    • and circulating factors promoting heterotopic ossification may be present in head injured patients.
       
  • Accelerated fracture healing and heterotopic ossifications are well-known phenomena in these patients with an ABI 41;42.
     
  • HO forms through a typical process beginning with the formation of osteoid to full calcification within a matter of weeks 35.
     
  • Over the next few months, the calcified osteoid remodels into well-organized trabecular bone at which point it is considered to have matured 35.
     
  • Several months after the initial trauma, these patients develop paraarticular and intramuscular bone formation and experience restricted range of motion, pain and ankylosis 30;36.
     
  • The bony lesion has been found to have a high metabolic rate, with a rate of bone formation more than three times greater than that of normal bone and an osteoclastic density of more than twice the number of osteoclasts found in normal bone 37.

For a more detailed discussion of HO post ABI see ERABI/Heterotopic Ossification and Venous Thromboembolism.

8.2.3   Clinical Presentation of Heterotopic Ossification (HO)

8.2.3.1   Location of Lesion

Which joints are most often involved in HO post TBI?

  1. The most commonly affected joints are the hip, then shoulders, elbows and rarely the knee.

The most commonly affected joint is the hip, then the shoulders, elbows and rarely the knee 30.

Hip Involvement

  • Hipinvolvement results in 18 to 37% restriction of range of motion 43
     
  • Total ankylosis of the joint occurs in 5-16% of affected hips 44.

Elbow Involvement

  • Sarafis et al. 43have noted that the distribution of HO around the elbow occurs most commonly either anteriorly in the flexor muscles or posteriorly in the extensors.
     
  • Ankylosis is most likely to occur in the elbow and it usually occurs posteriorly 30.

Knee Involvement

  • Sarafis et al. 43 have noted that theknee is a rare site of heterotopic ossification following head injury. The most common site in the knee is the inferomedial aspect of the distal femur.

How common is HO following TBI?

  1. The incidence of HO in TBI is 10-20%.
  • The incidence of heterotopic ossification in TBI patients is 10 to 20% 45;46 with the hip being the most frequent site of ossification.

8.2.3.2   Clinical Featuresof Heterotopic Ossification

Describe the clinical picture of HO post ABI.

  1. Clinical features of HO include a warm, swollen and painful joint often associated with decreased range of motion.
  • Pape et al. 36have noted that clinical examination may reveal a swollen, warm, painful joint which is often associated with a decreased range of motion. 
     
  • Watanabe and Sant 29have reported that the formation of HO generally precedes symptom onset with the earliest sign often being decreased range of motion in the involved joint. 
     
  • Other findings then include swelling, warmth, erythema, pain, palpation of a periarticular mass and fever47.It is therefore difficult to differentiate heterotopic ossification from infection because of the association with fever 30;46;48.
     
  • The clinical picture may be confused with deep venous thrombosis (DVT), a local infection, local trauma or fracture 49;50.

8.2.4   Diagnostic Tests for HO Post ABI

Describe those diagnostic tests which can be helpful in positively diagnosing HO post TBI?

  1. Plain radiographs are negative and remain negative until ossification occurs 4-6 weeks post injury.
     
  2. Serum level of alkaline phosphatase and the ESR may become elevated early on.
     
  3. Triple phase technetium-99 bone scan with increase uptake during the 1st and 2nd phases remains the gold standard, becoming positive about the same time as the clinical features occur.
  • Watanabe and Sant 29have noted that HO is generally initiated within 2-3 weeks of the onset of the injury; however, the onset has been reported 1 to 7 months following the TBI 31.
     
  • During the initial presentation, plain radiographs may be negative and will usually remain normal until ossification begins 4-6 weeks post injury.
     
  • Serum levels of alkaline phosphatase and the erythrocyte sedimentation rate may become elevated early on.
     
  • The triple phase technicium-99 bone scan with increased uptake during the first and second phases remains the diagnostic gold standard, becoming positive at about the same time as clinical features occur. 

8.2.5   Treatment of HO Post-Head Injury

What prophylactic treatments are available for treatment of HO post ABI?

  1. Range of motion exercises - There is Level 4 evidence that forceful manipulation  under general anesthesia increases range of motion in patients with heterotopic ossification following brain injury.
     
  2. Nonsteroidal anti-inflammatory medications
     
  3. Low-dose radiation
     
  4. Warfarin
     
  5. Etridonate disodium (EHDP)
  • Watanabe and Sant 29have noted that prophylactic treatment options include range of motion exercises, nonsteroidal anti-inflammatory medications (NSAIDs), low-dose radiation, warfarin, and etridonate disodium (EHDP)

Physiotherapy and Range of Motion Exercises

  • Range of motion exercises has been somewhat controversial with some earlier reports suggesting that physical therapy might actually contribute to HO 51;52.
     
  • More recently there has been a trend towards utilizing physical therapy with range ofmotion exercisesand even manipulation under anaesthesia of the involved joints46;53 to help prevent ankylosis. 
     
  • Pape et al. 36have noted that for HO, careful and judicious use of physiotherapy involving assisted range of motion exercises and gentle stretching has been shown to be of benefit 54.
     
  • However care should be taken not to move the joint beyond its pain-free range ofmovementas this can exacerbate the condition 55

Nonsteroidal Anti-Inflammatory Medications

  • The evidence for NSAIDs being used in prophylactic treatment of HO comes mostly from the use of indomethacin or ibuprofen prophylaxis against HO in patients following total hip arthroplasty (THA) 56;57.
     
  • Although it has been noted that these medications offer a significant benefit in prophylaxis of THA, the correlation of these findings to traumatic brain injuries is not known 29.

EHDP (Ethylhydroxybiphosphonate)

  • Watanabe and Sant 29have noted that biphosphonates, in particular etridonate (EHDP) in the prophylaxis and treatment of HO is controversial.
     
  • EHDP works by preventing the aggregation, growth and mineralization of calcium hydroxyapatite crystals which are essential for bone formation.
     
  • The majority of the research has been conducted with spinal cord injured individuals and with mixed results.
     
  • One prospective controlled trial examined the effectiveness of EHDP treatment for the management of HO following brain injury 58.
  • Results indicate thatthose in the EHDP groupshowed a significantly lower incidence of HO when compared with the control group

 

For further details on the literature discussing the effectiveness of EHDP and other therapeutic treatments of HO post ABI please see ERABI/Heterotopic Ossification and Venous Thromboembolism.

8.2.6   Surgical Excisionof HO Post ABI

Does surgical excision of HO post ABI improve clinical outcomes?

  1. There is Level 4 evidence that surgical excision of heterotopic ossification improves clinical outcomes.
  • Surgical excision of the heterotopic bone has been suggested as a possible option for those in whom heterotopic ossification has generated marked functional impairment or ulcers in the skin due to deformity 29.
     
  • According to expert opinion, surgical treatment should be considered only after 12-18 months to ensure that the bone tissue has matured, and to reduce the likelihood of recurrence 31;59.
     
  • There are some indications that EHDP and NSAIDs may be useful in preventing HO recurrence following surgical excision 29, although further studies are still needed to corroborate this claim. 
     
  • Watanabe and Sant 29 have reported that recurrence of HO following surgical excision usually occurs within 3 months post-operatively.