The formation of HO in trauma patients is critically discussed in the context of fracture healing. The role of severe head trauma was described in former studies [1, 14, 15, 24]. Studies on the influence of multiple trauma in combination with severe head trauma were performed in our department [5, 7] and confirmed the role of head injuries in polytrauma, too. In the present setting, we addressed the question of the impact of the applied surgical therapy of long bone fractures in polytrauma patients on the development of symptomatic HO. In the present setting, we specifically focussed on symptomatic HO. This is important due to the fact that only these patients are suffering from the HO. The patients included in our study are representative for patients suffering from the complaints following major trauma. The need for diagnostic and sometimes therapeutic interventions in these patients is crucial and towards symptomatic HO difficult. Therefore, we could not demonstrate an over-all incidence of heterotopic ossification. In our understanding, inappearant HO should not be treated and are to categorize as diagnostic findings by chance.
The present study is a retrospective single centre analysis of prospectively collected patient data. Demographic and injury related data of our patients are similar to those published before: Multiply injured patients commonly group around the age of 30 to 40 years with a predominance of males as do our patients. Overall injury severity and injury pattern are consistent with other cohorts . Similarly, the GCS of our patients is comparable to data of other authors [26, 27].
Furthermore, good comparison of patient groups seems possible because treatment strategy was very consistent in our centre over the inclusion period. Required data were documented completely for all of the individuals. Two independent examiners of the x-rays lead to similar results. Overall, we feel that our analysis safely leads to the following results:
In polytrauma patients, plate osteosynthesis is followed by larger HO formations compared to intramedullary nailing.
Patients treated with intramedullary nails more commonly showed HO formations remote to the fracture site.
Nonetheless, there are some limitations to our study. Heterotopic ossifications were essentially described by Brooker et al. This classification system includes the HO around the hip joint and is now widely accepted for classification following acetabular fracture treatment and arthroplasty of the hip. To classify the functional status of the hip joint, the Harris score is widely known. Further classifications were developed for the elbow, this score is divided into radiologic and functional aspects . Since there is no general classification system for all the joints, we transferred the Brooker criteria for the four different classes accordingly to the large joints of the extremtities.
Effects of injury pattern
The role of head injuries in the formation of HO still is lively debated about in the literature. Some authors reported a stimulation of fracture healing in patients with head injuries [29–31]. Furthermore, a positive correlation of the severity of the head injury and the HO rate was observed . Other studies could not confirm a relationship between severe head trauma and HO formation. Lehmann et al. demonstrated constant expressions of the HO in multiply injured patients without head trauma in comparison to multiply injured patients with severe head trauma . We could confirm the findings of Lehmann et al., the present report could demonstrate comparable GCS and constant incidence of head trauma in both groups.
Interestingly, a recent study demonstrated differences in the location of the HO between polytrauma patients with and without severe head trauma. In polytrauma patients with associated head trauma, the HO was located adjacent to the fracture region. In polytrauma patients without head injury, the HO formation more frequently occurred at sites remote to the actual fracture sites . In our study, the incidence and severity of head injuries was distributed equally between both groups.
Nonetheless, we found a higher incidence of remote HO in the IMN group, leading to the idea of systemic factors liberated during nailing that affect HO formation such as prostaglandin E2 [1, 3, 32].
Effects of treatment strategy
Surgical treatment such as osteosynthesis, manipulation at joints or traumatic haematoma is known to be a risk factor for the development of the HO [6, 33, 34]. In the present study, we could demonstrate a positive association of plate osteosynthesis and the development of the HO in the PLATE group.
A more invasive approach required for plate osteosynthesis is well described as one of the risk factors . Local fracture and soft tissue manipulation is believed to hold a substantial role in the development of the HO, possibly by the liberation of bone morphogenetic protein (BMP) or other tissue factors [35, 36]. Home et al reported on extended HO after intramedullary nailing in combination with severe head trauma . However, these results could not be shown in our study potentially due to a relatively low patient number.
Effects of additional therapy
In the present study, there were no significant differences in ventilation time (IMN: 12.2 ± 3.1 days vs. PLATE: 11.0 ± 2.7 days; p = 0.48). Long term ventilation is widely accepted as a factor associated with HO formation : One study showed HO in patients after pulmonary transplantation with prolonged ventilation times at healthy joints . Mechanical ventilation may lead to changes in the acid-base metabolism which results in mineral accumulation in the soft tissues and therefore may lead to HO formation  which was also demonstrated in an experimental study . Other authors speculate that HO formation in shock trauma patients and mechanically ventilated patients occurs due to critical hypoxia in consequence to local tissue compression. It could be revealed that osteogenesis is induced by low oxygen concentrations .
Effects of prophylactic medication
Prophylactic medications to prevent or to decrease HO are widely discussed in hip and acetabular surgery. Moreover, several studies revealed the effectiveness of prophylactic treatment after knee arthroplasty [18, 19, 39]. Prophylactic strategies may lead to decrease the development and the resulting size of the HO; these strategies include treatment with NSAID or postoperative radiotherapy. Best evidence for prophylactic medication is shown for indomethacine for at least 7 days, other NSAIDs are also well documented . To our knowledge, there are no reports on the effect of prophylactic medication on HO formation in multiple trauma patients. In our study, up to 30% (group PLATE) of the patients received prophylactic medications, there were no differences of NSAIDs prescribed (IMN: 22% vs. PLATE: 30%; p = 0.47).
The missing effect of the prophylactic treatment in our study may be the result of the low fraction of patients who received prophylactic treatment. On the other hand, HO formation in multiply injured patients may result out of interactions of multiple systemic and local factors, thereby limiting the effect of a single intervention or substance.