Gender and injury severity have been associated with the likelihood of developing HO following SCI (Krauss et al., 2014; Yolcu et al., 2020a). Specifically, Krauss et al. (2014) reported that males were five times more likely to develop HO compared to their female counterpart. in addition, a case series and a recent meta-analysis showed that patients with complete SCI were at greater risk of developing HO than those with incomplete SCi (Krauss et al., 2014; Yolcu et al., 2020a). Level of injury as a risk factor was highlighted by Ranganathan et al. (2015) whose literature review revealed that injuries to the thoracic and cervical spine are greater risk of developing HO. However, it should be noted both gender and injury severity as risk factors have been disputed in the literature (Krauss et al. 2014).
Krauss et al. (2014) also investigated the role of hyper-coagulable states and related blood markers as risk factors in the development of HO. D-Dimer was elevated in 24 out of 32 patients with SCI and concurrent HO. Following this, the role of deep vein thrombosis (DVT) and pulmonary embolism (PE) have also been linked to the development of HO. Reznik et al. (2014) reported that DVT/PE were significant predictors of HO along with multiple pressure ulcers and AIS B severity score. Reznik et al. (2014) propose that the association of HO and DVT/PE is due to the link between trauma/surgery/fractures and stimulation/increase in thrombogenic factors such as thromboplastin or factor III. The association between DVT and HO, however, was not identified in the meta-analysis by Yolcu et al. (2020a) examining current evidence on risk factors associated with HO post-SCI.
The link between the presence of pressure ulcers and development of HO in the SCI population has also been shown in a case series by Rawat et al. (2019). The relationship between HO and pressure ulcers is thought to be due to pressure ulcer infection deep enough to reach the bone. Along with tissue hypoxia, prolonged immobilization and muscle trauma, these factors combine to increase the risk of HO formation (Emami Razavi et al. 2015). Further research is required to solidify the relationship between HO and pressures sores/ulcers.
An observational study by McKean et al. (2021) evaluated pelvic magnetic resonance imaging muscle signal changes and their association with early HO in 40 patients within the first six months post-SCI. The findings demonstrated that Increased T2 muscle signal was common following SCI and was linked to early MR signs of HO among patients.
Recently, a number of studies have also examined potential biological factors that contribute to the development of neurogenic heterotopic ossification (Egan, Duque, Keenan & Pignolo, 2018; Povoroznyuk, Bystrytska, Balatska, 2017). A study by Egan et al. (2018) evaluated the presence of circular osteogenic precursor cells (COP bone marrow-derived type 1 collagen+CD45+) in incidences of non-hereditary HO. All tissue samples collected revealed the presence of COP cells. As these hematopoietic-derived cells were shown to both migrate to inflammatory sites and have osteogenic potential, there is the possibility to use COP cell count as an indicator of the risk for HO development post-SCI (Egan et al., 2018). Another study by Povoroznyuk et al. (2017), identified that the serum marker procollagen type 1 N- terminal propeptide (P1NP) for bone formation was the specific bone turnover marker implicated in HO formation. It was concluded that concentrations of 187.3 ng/mL or higher could be used as an early indicator of HO (Povoroznyuk et al., 2017).
Between 3-12 weeks, symptoms of HO start to appear (Schuetz et al. (2005). The initial clinical signs of inflammation are non-specific for HO (Neal 2003). Individuals typically present with 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), and a possible reduction in mobility at the HO site (Brady et al., 2018). Conversely, some SCI patients do not experience any pain. Skeletal bio-markers can help detect development of HO, in particular, ALP serum, CPK, C-reactive protein, prostaglandin E2, and erythrocyte sedimentation rate which have been associated with HO after SCI (Ploumis et al. 2015).