1. Background
One complication that can occur after spinal cord injury (SCI) is heterotopic ossification (HO). HO is the formation of a lamellar bone within the soft tissues surrounding peripheral joints (1). Its prevalence ranges from 10% - 78% (2, 3), and its exact etiology is unknown. Mesenchymal metaplasia, bone metabolism, and joint trauma have been considered to have roles in developing HO (4-6). HO can occur in any joint but most commonly occurs in the hip joint and sometimes occurs in the joints of the shoulders, knees, and elbows (7, 8). It will cause limitation of range of motion and ankylosis, which will negatively impact the rehabilitation processes (9). The exact etiology and pathogenesis of HO are unclear, but some clinical factors have been considered to contribute to development of HO such as sex, age, completeness of the injury, spasticity, and presence of pressure sores (8, 9).
2. Objectives
As studies evaluating hip ossification in Iranian patients with SCI are limited, we designed this study to evaluate the prevalence of HO in cases with SCI and clinical factors related to this finding.
3. Patients and Methods
In this cross-sectional study conducted in Imam Hospital (affiliated hospital to Tehran University of Medical Sciences) between September 2012 and September 2013, 135 patients with traumatic SCI who were referred to a SCI clinic were enrolled. All patients were asked to complete informed consent forms before entering the study.
A structured questionnaire was applied to collect information regarding demographic data, level of injury, the American Spinal Injury Association (ASIA), complete or incomplete lesions, cause of injury, history of urinary tract infection (UTI), kidney and bladder stones, deep vein thrombosis (DVT), spasticity, and bedsore. Hip radiography was performed for all patients to evaluate hip ossifications. An expert radiologist assessed the obtained radiographs.
Spasticity of the limbs was assessed using the Ashworth scale. The scores range from zero (flaccid, F, or zero) to 4 (the affected joint is rigid in flexion or extension) (10).
Statistical analyses were performed using SPSS software version 18.0 (statistical product and service solutions, SSPS Inc., Chicago). Results are presented as mean ± SD. The Student’s t-test was used for continuous variables, and the Pearson χ 2 test and Fisher’s exact test were applied for categorical variables. Logistic regression analysis was conducted by considering HO as a dependent variable. P-value < 0.05 was considered statistically significant.
4. Results
One hundred and thirty-five patients were enrolled in this study. Thirty-one (23%) were women and 104 (77%) were men. The most common cause of injury was accident (66.7%) followed by a fail (28.1%) (Table 1).
Table 1. Disease-related Variables in Patients a
| Variables | Values |
|---|---|
| Asia | |
| A | 77 (57) |
| B | 28 (20.7) |
| C | 26 (19.3) |
| D | 3 (2.2) |
| E | 1 (0.7) |
| Complete or incomplete lesions | |
| Complete paraplegia | 74 (54.8) |
| Incomplete paraplegia | 25 (18.5) |
| Complete quadriplegia | 13 (9.6) |
| Incomplete quadriplegia | 23 (17) |
| Level of injury | |
| Cervical | 41 (30.4) |
| Thoracic | 84 (62.2) |
| Lumbar | 10 (7.4) |
| Immobility | |
| Yes | 87 (64.4) |
| No | 48 (35.6) |
| UTI | |
| Yes | 80 (59.3) |
| No | 55 (40.7) |
| Kidney stone | |
| Yes | 17 (12.6) |
| No | 118 (87.4) |
| Bladder stone | |
| Yes | 12 (8.9) |
| No | 123 (91.1) |
| DVT | |
| Yes | 7 (5.2) |
| No | 128 (94.8) |
| Spasticity | |
| Yes | 60 (44.4) |
| No | 75 (55.6) |
| Bed sore | |
| Yes | 42 (31.1) |
| No | 93 (68.9) |
a Data are presented as No. (%).
Spasticity was reported in 60 (44.4%) of cases while bedsore was found in 42 (31.1%). Grade of spasticity was 1 in 14 (23.3%), 2 in 33 (55%), 3 in 9 (15%), and 4 in 4 (6.7%). HO present in 51 (37.8%) patients and hip radiography showed normal results in 84 (62.2%) patients. Duration of injury and bed sores were significantly higher in patients with HO (Table 2). Logistic regression analysis considering HO as a dependent variable showed that only bedsore was an independent predictor of HO (Table 3).
Table 2. Categorical Variables in Patients With and Without HO
| Variables | With HO a | Without HO a | P Value |
|---|---|---|---|
| Age, y | 36.9 ± 13.7 | 33.1 ± 12.9 | 0.1 |
| Duration of Injury, mo | 62 ± 59 | 45.9 ± 39.2 | 0.04 |
| Level of injury | 0.1 | ||
| Cervical | 16 | 25 | |
| Thoracic | 34 | 50 | |
| Lumbar | 1 | 9 | |
| Immobility | 0.4 | ||
| Yes | 31 (23) | 56 (41.5) | |
| No | 20 (14.8) | 28 (20.7) | |
| UTI | 0.7 | ||
| Yes | 31 (23) | 49 (36.3) | |
| No | 20 (14.8) | 35 (25.9) | |
| Kidney stone | 0.3 | ||
| Yes | 8 (5.9) | 9 (6.7) | |
| No | 43 (31.9) | 75 (55.6) | |
| Bladder stone | 0.7 | ||
| Yes | 5 (3.7) | 7 (5.2) | |
| No | 46 (34.1) | 77 (57) | |
| DVT | 0.2 | ||
| Yes | 4 (3) | 3 (2.2) | |
| No | 47 (34.8) | 81 (60) | |
| Spasticity | 0.9 | ||
| Yes | 23 (17) | 37 (27.4) | |
| No | 28 (20.7) | 47 (34.8) | |
| Bed sore | 0.006 | ||
| Yes | 23 (17) | 19 (14.1) | |
| No | 28 (20.7) | 65 (48.1) |
a Data are presented as No. (%) or mean ± SD.
Table 3. Logistic Regression Analysis Considering HO as a Dependent Variable
| Variable | OR | 95% CI | P Value |
|---|---|---|---|
| Immobility | 0.6 | (0.2 - 1.3) | 0.2 |
| UTI | 1.1 | (0.5 - 2.4) | 0.7 |
| Kidney stone | 1.3 | (0.4 - 4.3) | 0.5 |
| Bladder stone | 0.8 | (0.2 - 3) | 0.7 |
| DVT | 1.6 | (0.3 - 8.4) | 0.5 |
| Spasticity | 1 | (0.5 - 2.2) | 0.8 |
| Bed sore | 3.1 | (1.4 - 7) | 0.004 |
5. Discussion
The current study found that prevalence of HO in cases with traumatic SCI is 37.8%, which is within the accepted range. In previous studies, prevalence of HO in cases with SCI was reported to be between 12% and 40% (8, 11-13). We also found that injury duration was significantly higher in cases with HO, and the presentation of HO has been correlated with pressure sores. These findings are compatible with the findings of Bravo-Payno et al. In their study, 13% of patients with SCI had HO, and presence of pressure sores significantly correlated with HO (8). Contrary to our findings, they found that complete spinal lesion and spasticity are correlated with HO presentation. In a previous study, Coelho and Beraldo found that spasticity, number of pressure ulcers, and time elapsed since the injury are independently associated with HO (9).
In other studies, patients with complete transverse spinal lesions were at a higher risk of developing HO than other patients (12, 14, 15), but our results did not confirm this finding. The only predicting factor for HO in the current study was pressure sore, which is compatible with previous studies (8, 14, 16). Pressure sores could occur before or after the onset of HO while it has been reported that HO occurs in the first two months after SCI below the level of injury (2). Some authors believe that rapid admission of a patient with SCI to a specialized hospital will reduce the risk of developing HO (6, 8). On the other hand, Bravo-Payno found that an increase in delay to reach a specialized hospital increased the number of pressure sores in cases (8). Additionally, they found that, if pressure sores occur during an early phase, it could influence the development. of HO. It may be that a common etiology plays a role in developing both, HO and bed sores. Pressure, friction or muscular trauma, lack of special care, and tissue infection are among the common causes of bed sores (8) while hypercalcemia, tissue hypoxia, changes in sympathetic nerve activity, prolonged immobilization, and mobilization after prolonged immobilization are among risk factors for the development of HO (17). It may be that HO develops after the formation of pressure sores when the infection penetrates the deep tissues, up to the bone.
Special care after SCI may prevent the development of HO and bed sores. The other risk factor for HO development in previous studies was spasticity; however, our results did not confirm spasticity as a risk factor for developing HO.
In the study by Bravo-Payno et al. spasticity was 2 times higher in cases with HO than in cases without HO (8), and the odds of spasticity were 3.8 times higher in HO patients in a study conducted by Coelho and Beraldo (9). Lal et al. found spasticity in 84% vs. 54% of patients with SCI with and without HO (14).
Trauma, manipulations, and intense spasticity in patients with SCI may result in formation of hematomas and para-articular microhematomas. These formations will be calcified and ossify through metaplasia of the mesenchymal cells (8).
We also found that gender, level of injury, and presence of urinary tract complication and DVT are not significantly different in patients with and without HO, but injury duration is significantly higher in cases with HO, confirming Coelho and Beraldo’s findings (9).
This article had some limitations. First, it was conducted in a tertiary hospital. Second, we used X-ray for HO diagnosis. Therefore, some patients in early stages may have been missed. Multi-centric studies with large sample sizes using CT scan as a diagnostic tool are recommended. Evaluation for hip ossification should be considered in patients with SCI.
