Is there clinical evidence to recommend use of Bisphosphonates in the treatment of early heterotopic ossification in a patient with acquired brain injury 3 months ago?

Comment by InpharmD Researcher

One study observed the use of disodium etidronate as a prophylactic agent for heterotopic ossification in patients with recent brain injury. While development of ossification was favored in the group receiving etidronate, the study was of low quality and presented results from a small patient population. Further data is needed to conclude whether bisphosphonates are truly beneficial.
Background

A systematic review observing treatment of heterotopic ossification in traumatic brain injury patients identified one article which administered etidronate in patients with acquired brain injury within a week of injury. The bisphosphonate was administered as a prophylactic agent rather than treatment (Table 1). [1]

References:

[1] Aubut JA, Mehta S, Cullen N, Teasell RW; ERABI Group; Scire Research Team. A comparison of heterotopic ossification treatment within the traumatic brain and spinal cord injured population: An evidence based systematic review. NeuroRehabilitation. 2011;28(2):151-160. doi:10.3233/NRE-2011-0643
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

Is there clinical evidence to recommend use of Bisphosphonates in the treatment of early heterotopic ossification in a patient with acquired brain injury 3 months ago?

Please see Table 1 for your response.

 

Disodium etidronate: its role in preventing heterotopic ossification in severe head injury

Design

Prospective study

N=20

Objective

To determine the incidence of heterotopic ossification (HO) in the severe head injury population and to evaluate the prophylactic effect of disodium etidronate (EHDP) in decreasing incidence by initiating therapy in the acute phase of head injury management.

Study Groups

Non-treated group (n=10)

EHDP group (n=10)

Inclusion Criteria

 Initial Glasgow Coma Score (GCS) < 8, coma lasted longer than 2 weeks

Exclusion Criteria

 GCS no greater than three after 48 hours, awake from coma in less than 2 weeks, death 

Methods

All severe head injury patients from the previous 12 months not treated with EHDP were reviewed and matched to prospective subjects with matched GCS score and coma duration who received EHDP. Patients were started on EHDP 20 mg/kg/day for the first 12 weeks, followed by 10 mg/kg/day for the second twelve weeks, and were administered via nasogastric tube while maintained parenterally on crystalloid or hyperalimentation solutions. EHDP started two to seven days after injury with treatment designated for six months.

Duration

 6 months

Outcome Measures

 Development of heterotopic ossification

Baseline Characteristics

  

Non-treated group (n=10)

EHDP group (n=10)

Age, years

 27 31

Female

2 7

Associated fractures

 5 7

Length of coma

< 1 month

1 to 3 months

> 3 months

 

3

4

3

 

2

4

4

Type of injury

Focal

Diffuse

 

3

7

 

4

6

Limb spasticity

8

10

Results

Endpoint

Non-treated group (n=10)

EHDP group (n=10)

Development of heterotopic ossification

 7 (70%) 2 (20%)

Adverse Events

 N/A

Study Author Conclusions

 These data suggest that heterotopic ossification may be prevented by early use of EHDP, and the results warrant further clinical trials. 

InpharmD Researcher Critique

 This was an older trial that may not reflect current clinical practice. The study is hindered by a small population which prevents extrapolation of results. Though it appears that the group treated by EHDP observed less occurrence of heterotopic ossification, subsequent studies are needed to confirm these findings. 



References:

Spielman G, Gennarelli TA, Rogers CR. Disodium etidronate: its role in preventing heterotopic ossification in severe head injury. Arch Phys Med Rehabil. 1983;64(11):539-542.