Background

Stratifying patients with Low Back Pain (LBP) using the STarT Back Tool and delivering targeted treatment has demonstrated efficacy in individual physiotherapy settings. Physiotherapy interventions for LBP patients are often delivered in groups. This study aimed to explore the sustainability and cost effectiveness of a group stratified intervention in primary care.

Introduction: Patients with multiple skeletal injuries are susceptible to Systemic Inflammatory Response Syndrome (SIRS) and consequently Acute Respiratory Distress Syndrome (ARDS). Fracture haematoma contains pro-inflammatory mediators. The aim of our study was to show in vitro that fracture haematoma is implicated in neutrophil mediated injury, SIRS, ARDS and MOF.

Methods: Fracture haematoma was isolated from 10 patients at the time of surgery. Neutrophils (PMN) were isolated from 10 healthy volunteers. PMN were exposed to the fracture haematoma supernatant and PMN activation in both primed and unprimed neutrophils were examined (CD11b and CD18 adhesion receptor expression and respiratory burst). PMN phagocytosis and apoptosis were also assessed using flow cytometry. Transmigration across an endothelial barrier was also measured following exposure to fracture haematoma.

Results: Fracture haematoma had a marked effect on respiratory burst in primed PMNs (control = 100% vs 20% fracture haematoma = 1044% ± 405, p=0.04). CD11b and CD18 adhesion receptor expression were not upregulated in the fracture haematoma group. PMN phagocytosis of E coli was increased following treatment with fracture haematoma (control = 100% vs fracture haematoma = 171% ± 6SE, p=0.0001). Transendothelial migration of treated neutrophils was unaffected. Treatment of endothelial monolayers with fracture haematoma did not result in upregulated ICAM1 expression but was observed to induce significant endothelial cell death. PMN apoptosis was significantly delayed following exposure to fracture haematoma (control = 46% ± 5 vs fracture haematoma = 8% ±2, p=0.0005).

Discussion: We have shown that fracture haematoma activates neutrophils, increases phagocytosis and respiratory burst whilst delaying apoptosis. These effects, whilst beneficial at the site of injury, may cause neutrophil mediated tissue injury systemically.

Background: Low molecular weight heparins (LMWH) are of undoubted efficacy as thromboprophylaxis in orthopaedic surgical practice. However, prolonged dosage inhibits bone nodule formation in vitro and we have previously reported that daily dosing significantly delays fracture healing. To further investigate these phenomena we hypothesised that LMWH’s would reduce osteoblast survival and thus bone formation by inducing programmed cell death (apoptosis).

Methods: Primary human osteoblasts were isolated from femoral heads excised during hip arthoplasty and cultured to passage 3–5. These were examined for VEGF receptor expression using a biotinylated binding assay on flow cytometry. Osteoblasts were grown to confluence and then incubated for 24 hours in control medium or medium treated with enoxaparin (200 – 2X10(−4) IU/mL) or combination of enoxaparin (200 – 2X10 (−4) IU/mL) and VEGF (1ng/ml). Apoptosis was determined by measuring cytosolic histone-associated DNA fragmentation using an enzyme linked immunosorbant assay. Results were confirmed by DNA fragmentation analysis on agarose gel electrophoresis. Cell functional viability was measured by a tetrazolium bioreduction colorimetric assay.

Results: Data is expressed as percentage of control apoptosis or viability, illustrates mean ± s.e.m. and n=4 experiments in each case. ANOVA was employed for statistical analysis; *versus control, #versus enoxaparin treated; p< 0.05 was considered significant.

Conclusions: Therapeutic doses of LMWH attenuate osteo-blast survival by inducing significant apoptosis. This effect is partly abrogated by VEGF, which independently enhances osteoblast viability, thus delaying spontaneous and enoxaparin induced apoptosis. These findings may explain the bone resorptive effects of prolonged LMWH therapy and suggest a potential therapeutic role for VEGF in conditions of delayed bone formation.