Increased bone turnover and fracture healing is associated with acute spinal cord injuries. Experimental work to date has been confined to animal models. While the benefits in relation to quicker fracture healing are obvious, this excessive bone growth (heterotopic ossification) also causes unwanted side effects, such as decreased movement around joints, joint fusion and renal tract calculi.

This paper evaluates two groups of patients with spinal column fractures – those with neurological compromise and those without, and compares them with a control group with isolated long bone fractures. Serum was taken from these patients at 10 days post injury and was analysed for the known osteogenic cytokines Insulin-like Growth Factor-1 (IGF-1) and Transforming Growth Factor-b1 (TGF-b1) as well as being added to an osteoblast cell culture line to analyse cell proliferation.

The results for the IGF-1 show a higher level in the neurology group compared to the no neurology group (p=0.038). In the TGF-B1 assay, the neurology group has a lower level than the other two groups (p< 0.0001 and p=0.002 respectively). However, when this group is subdivided into patients with complete and incomplete neurology, it can be seen that the levels of the complete group are elevated, although not significantly so (p=0.228).

All three groups stimulated markedly increased osteoblast cell proliferation versus a control group (p=0.086, p=0.005 and p=0.002 respectively). However, the neurology group is significantly lower than the other two groups (p=0.007 and p=0.001 respectively). Furthermore the complete group causes a lower proliferation rate than the incomplete group (p=0.539).

In conclusion, at 10 days post injury when the acute inflammatory reaction is subsiding and new bone is being laid down, patients with acute spinal cord injuries have increased bone turnover. This increase is being indirectly mediated by IGF-1, and more elevated levels with more severe neurological compromise suggest a contributory role of TGF-b1. Direct stimulation of osteoblasts does not appear to have any role to play in this accelerated bone healing.

Patients with spinal cord injuries have been seen to have increased healing of attendant fractures. This for the main has been a clinical observation with laboratory work confined to rats. While the benefits in relation to quicker fracture healing are obvious, this excessive bone growth (heterotopic ossification) also causes unwanted side effects, such as decreased movement around joints, joint fusion and renal tract calculi. However, the cause for this phenomenon remains unclear.

This paper evaluates two groups with spinal column fractures – those with neurological compromise (n=10) and those without (n=11), and compares them with a control group with isolated long bone fractures (n=10). Serum was taken from these patients at five specific time intervals post injury (1 day, 5 days, 10 days, 42 days (6 weeks) and 84 days(12 weeks)). These samples were then analysed for levels of Transforming Growth Factor-Beta (TGF-b) using the ELISA technique. This cytokine has been shown to stimulate bone formation after both topical and systemic administration.

Results show TGF-b levels of 142.79+/−29.51 ng/ml in the neurology group at 84 days post injury. This is higher than any of the other time points within this group (p< 0.001 vs. day 1, day 5 and day 10 and p=0.005 vs. 42 days, ANOVA univariate analysis). Furthermore, this level is also higher than the levels recorded in the no neurology (103.51+/−36.81 ng/ml) and long bone (102.28=/−47.58 ng/ml) groups at 84 days post injury (p=0.011 and p=0.021 respectively, ANOVA univariate analysis). There was statistically significant difference in TGF-b levels seen between the clinically more severely injured patients i.e. complete neurological deficit and the less severely injured patients i.e. incomplete neurological deficit.

In conclusion, the results of this work, carried out for the first time in humans, offers strong evidence of the causative role of TGF-b in the increased bone turnover and attendant complications seen in patients with acute spinal cord injuries.