Intervention of Heterotopic Ossification Post Head Injury

Prophylactic treatment options for HO include range of motion exercises, nonsteroidal anti-inflammatory medications, low-dose radiation, warfarin, and etidronate disodium (EHDP) (Watanabe & Sant 2001).

Physiotherapy and Range of Motion Exercises

At one time, the literature on range of motion therapy post acquired brain injury (ABI) suggested that such experiences actually contributed to the development of HO (Chantraine & Minaire 1981; Crawford et al. 1986). A shift in thinking practice then occurred towards the utilization of range of motion exercises, and even joint manipulation under anesthesia, to help prevent ankylosis in patients with ABI (Garland 1991; Garland et al. 1982). Pape et al. (2004) have noted that for HO, careful and judicious use of physiotherapy, involving assisted range of motion exercises and gentle stretching, are beneficial. However, it has been cautioned that care should be taken not to move the joint beyond its pain-free range of movement as this can exacerbate the condition (Evans 1991; Pape et al. 2004).

Table: Physiotherapy and Range of Motion Exercises as Treatment for Heterotopic Ossification


Research in this area is limited; however, case study examples have shown physiotherapy with assisted range of motion to be beneficial (Ellerin et al. 1999). Garland et al. (1982) conducted a review of patients with TBI who underwent forceful manipulation of joints with pre-existing HO under anesthesia and reported that it was useful in maintaining and increasing range of motion. With 82% of joints having increased range of motion, the authors concluded that forceful manipulation is not only useful in maintaining motion but also aids in the prevention of bony ankylosis and did not appear to exacerbate the ossification process (Garland et al. 1982; Garland & Varpetian 2003). Garland and Varpetian (2003) also noted that patients with ABI frequently suffer from spasticity, intolerance to pain and voluntary muscle guarding. As a result, anesthesia may be needed to help differentiate between spasticity and ankylosis and to allow sufficient muscle relaxation to perform the joint manipulation (Garland & Varpetian 2003).


There is Level 4 evidence that forceful manipulation under general anesthesia increases range of motion in patients with heterotopic ossification following brain injury.


Forceful joint manipulation increases range of motion in heterotopic ossification.


Careful use of physiotherapy with assisted range of motion exercises and gentle stretching are beneficial for heterotopic ossification.


Continuous Passive Motion

Continuous passive motion devices have shown promising results in maintaining range of motion following total knee replacement (Nadler et al. 1993; Salter 1996). Animal data shows that continuous passive motion does not increase the progression of HO (Van Susante et al. 1996). Moreover, there is little human research evidence that HO is worsened by passive range of motion (Linan et al. 2001). Several studies have examined continuous passive motion in combination with surgical excision. These studies are explained further in section 11.4. Further research is needed in the ABI population.


Continuous passive range of motion devices may increase range of motion.


 Nonsteroidal Anti-Inflammatory Drugs

The evidence for nonsteroidal anti-inflammatory medications as prophylactic treatment for HO comes mostly from the use of indomethacin or ibuprofen in patients following total hip arthroplasty (Kjaersgaard-Andersen & Schmidt 1986; Ritter & Sieber 1985). Although it has been reported that the prophylactic use of these medications significantly decreases HO formation following total hip arthroplasty, it is not known if they have the same effect in the ABI population. 

Disodium Etidronate (EHDP)

The use of EHDP, a bisphosphate, in the prophylaxis and treatment of HO is controversial (Watanabe & Sant 2001). EHDP works by preventing the aggregation, growth and mineralization of calcium hydroxyapatite crystals which are essential for bone formation. EHDP may potentially delay fracture healing, as long-term use has been associated with osteomalacia. 

Individual Studies

Table: Prophylactic Treatment of Heterotopic Ossification with Etidronate


Although EHDP has been shown to be effective in reducing HO in other populations, such as spinal cord injury, its effectiveness among individuals with brain injury is less studied. In an ABI population, Spielman et al. (1983) found that patients treated with EHDP showed a significantly lower incidence of HO than the control group. However, due to the small sample size of the study and the research design, additional research assessing the benefit of EHDP for the intervention of HO following brain injury is needed.


There is Level 2 evidence that Disodium Etidronate (EHDP) reduces the development of heterotopic ossification in patients with severe head injury. 


Disodium Etidronate prevents the development of heterotopic ossification.


Surgical excision

Surgical excision of the heterotopic bone has been suggested as a possible option for those in whom HO has generated marked functional impairment or ulcers in the skin due to deformity (Watanabe & Sant 2001). It had been suggested, based on expert opinion, that surgical intervention be considered only 12 to 18 months after HO initiation to ensure that the bone tissue has matured, and to reduce the likelihood of HO recurrence (Garland 1991; Sazbon et al. 1981). The issue of timing is controversial and has changed in recent years (Moreta & De los Mozos 2014). There is some indication that EHDP and nonsteroidal anti-inflammatory medications may be useful in preventing HO recurrence following surgical excision (Watanabe & Sant 2001). Further studies are needed to corroborate this. Watanabe and Sant (2001) have reported that recurrence of HO following surgical excision usually occurs post-operatively within three months.  

Individual Studies

Table: Surgical Excision of Heterotopic Ossification


Thirteen studies examined the effects of surgical excision of HO: two studies focused on the shoulder (Fuller et al. 2013; Pansard et al. 2013), three on the elbow (De Palma et al. 2002; Ippolito et al. 1999a; Lazarus et al. 1999), one on the hips (Ippolito et al. 1999a), three for the knees (Charnley et al. 1996; Fuller et al. 2005; Ippolito et al. 1999b) and three examined a combination of joints (Kolessar et al. 1996; Melamed et al. 2002; Moore 1993).

In many studies, the recurrence of HO was evaluated months following the initial operation, with rates ranging from 0 to 27% (Fuller et al. 2013; Fuller et al. 2005; Ippolito et al. 1999a, 1999b; Moore 1993; Pansard et al. 2013). The majority of the studies did not specify what qualified as recurrence; however a study by Kolessar et al. (1996) found recurrence rates differed based on the classification system utilized (23.8% versus 4.8% using the Brooker classification and the Stover and colleagues classification, respectively). A systematic review conducted by Lee et al. (2013) focused specifically on the surgical excision of HO in the elbow and found improvements in motion, with low levels of recurrence (14.3%). However, complications such as fracture, infection, nerve palsies, wound complications and loss of motion without recurrence were found in 27.5% of cases (Lee et al. 2013).

Overall, the surgical excision of HO resulted in improved range of motion. One study did note a decrease in range of motion for a small portion of participants (Ippolito et al. 1999a). Improvements in activities of daily living and ambulation were also found (Fuller et al. 2005; Ippolito et al. 1999a, 1999b; Melamed et al. 2002). It is worth noting that length of time between injury and surgical resection was found to be a significant predictor of outcome, as longer times were associated with less improvement (Lazarus et al. 1999). Although therapy was provided after the surgery in many of the studies, only one study formally evaluated its effectiveness. The study conducted by Lazarus et al. (1999) found that patients who had continuous passive motion exercises post operatively made significantly greater gains those individuals who did not (57.9° versus 24.1°, p=0.04).


There is Level 4 evidence that surgical excision of heterotopic ossification improves clinical outcomes.


Surgical excision of heterotopic ossification improves range of motion.