Injuries to the spinal cord may be associated with increased healing of fractures. This can be of benefit, but excessive bone growth can also cause considerable adverse effects.

We evaluated two groups of patients with fractures of the spinal column, those with neurological compromise (n = 10) and those without (n = 15), and also a control group with an isolated fracture of a long bone (n = 12). The level of transforming growth factor-beta (TGF-β), was measured at five time points after injury (days 1, 5, 10, 42 and 84).

The peak level of 142.79 ng/ml was found at day 84 in the neurology group (p < 0.001 vs other time points). The other groups peaked at day 42 and had a decrease at day 84 after injury (p ≤ 0.001).

Our findings suggest that TGF-β may have a role in the increased bone turnover and attendant complications seen in patients with acute injuries to the spinal cord.

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-ß) using the ELISA technique. This cytokine has been shown to stimulate bone formation after both topical and systemic administration.

Results show TGF-ß 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 non 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-ß levels seen between the clinically more severely injured patients, ie complete neurological deficit and the less severely injured patients, ie 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-ß in the increased bone turnover and attendant complications seen in patients with acute spinal cord injuries.

This basic science study attempts to explain why patients with spinal cord injuries have been seen to display increased healing of attendant fractures.

For the main part, this 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 group 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 (24hrs, 120hrs, 10 days, 6 weeks and 12 weeks). The time period most closely related to the end of the acute inflammatory reaction and the laying down of callus was the 10-day post injury time period.

Serum samples taken at this time period were analysed for IGF-1 and TGF-ß levels, both known to initiate osteoblastic activity, using ELISA kits. They were also exposed to an osteoblast cell culture line and cell proliferation was measured.

Results show that the group with neurology has increased levels of IGF-1 compared to the other groups (p< 0.14, p< 0.18 respectively, Student’s t-test) but had lower TGF-ß (p< 0.05, p< 0.006) and osteoblast proliferation levels (p< 0.002, p< 0.0001). When the neurology group is subdivided into complete (n=5) and incomplete (n=5), it was shown that the complete group had higher levels of both IGF-1 and TGF-ß. This trend is reversed in the osteoblast proliferation assay.

This work, for the first time in human subjects, identifies a factor which may be regulating this complication of acute spinal cord injuries, namely IGF-1. Furthermore, the observed trend in the two cytokines seen in the complete neurology group may suggest a role for TGF-ß. However, the results do show that a direct mediation of this unwanted side effect of spinal cord injuries is unlikely as seen in the proliferation assay. Further work remains to be done to fully understand the complexities of the excessive bone growth recognised in this patient group.

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 (24hrs, 120hrs, 10 days, 6 weeks and 12 weeks). The time period most closely related to the end of the acute inflammatory reaction and the laying down of callus was the 10-day post injury time period.

Serum samples taken at this time period were analysed for IGF-1 and TGF-β levels, both known to initiate osteoblastic activity, using ELISA kits. They were also exposed to an osteoblast cell culture line and cell proliferation was measured.

Results show that the group with neurology has increased levels of IGF-1 compared to the other groups (p< 0.14, p< 0.18 respectively, Student’s t-test) but had lower TGF- (p< 0.05, p< 0.006) and osteoblast proliferation levels (p< 0.002, p< 0.001), despite having a significantly higher cell proliferation than a control group (p< 0.0001). When the neurology group is subdivided into complete (n=5) and incomplete (n=5), it was shown that the complete group had higher levels of both IGF-1 and TGF-. This trend is reversed in the osteoblast proliferation assay.

This work, for the first time in human subjects, identifies a factor which may be regulating this complication of acute spinal cord injuries, namely IGF-1. Furthermore, the observed trend in the two cytokines seen in the complete neurology group may suggest a role for TGF-β. However, the results do show that a direct mediation of this unwanted side effect of spinal cord injuries is unlikely as seen in the proliferation assay. Further work remains to be done to fully understand the complexities of the excessive bone growth recognised in this patient group.

Herniated intervertebral disc tissue has been shown to produce a number of proinflammatory mediators and cytokines, but there have been no similar studies using discs from patients with discogenic low back pain.

We have compared the levels of production of interleukin-6 (IL-6), interleukin-8 (IL-8) and prostaglandin E₂ (PGE₂) in disc tissue from patients undergoing discectomy for sciatica (63) with that from patients undergoing fusion for discogenic low back pain (20) using an enzyme-linked immunoabsorbent assay.

There was a statistically significant difference between levels of production of IL-6 and IL-8 in the sciatica and low back pain groups (p < 0.006 and p < 0.003, respectively).

The high levels of proinflammatory mediator found in disc tissue from patients undergoing fusion suggest that production of proinflammatory mediators within the nucleus pulposus may be a major factor in the genesis of a painful lumbar disc.