Introduction

Lower limb open fractures are severe injuries, with a joint orthoplastic approach for management recommended by BOAST. An initial audit highlighted a discrepancy in time to definitive wound coverage between the Queen Elizabeth University Hospital (QEUH), which at the time was not an orthoplastic centre, and the Glasgow Royal Infirmary (GRI) which was. Our aim was to perform a secondary audit to identify if the introduction of an orthoplastic service at the QEUH led to a reduction in time to definitive wound coverage.

Introduction Bone loss and increased bone fragility may occur following long-term steroid therapy resulting in painful vertebral fractures. To fully understand the mechanisms underlying steroid-induced osteoporosis and to test potential spinal implants a large animal model is needed. The sheep is appropriate since bone remodelling is similar to humans and the vertebral body dimensions permit easy surgical manipulation. This study was undertaken to fully characterise the sheep as a model of steroid-induced vertebral osteoporosis and to evaluate its suitability for testing balloon kyphoplasty.

Methods Osteoporosis was induced in ten lactating ewes (mean age 8 years) by ovariectomy, weekly injection of 54mg dexamethasone (Dexafort, Intervet, Australia) and a diet containing 0.2% calcium for up to 6 months. Baseline and endpoint iliac crest biopsies were taken to measure static histomorphometric indices of bone formation and resorption. Control animals were not ovariectomised and not treated with steroids. Dual energy X-ray absorptiometry (DXA, Hologic QDR 1000+, USA) was used to monitor bone mineral density (BMD) in the lumbar spine (L2-L5) after 0, 3 and 6 months of steroid treatment. At each time interval sheep were killed by barbiturate injection and the entire lumbar spine (L1-L6) was processed for histology, quantitative histomorphometry, mechanical testing, micro-CT (computed tomography) and ex-vivo trials to inflate kyphoplasty balloon tamps.

Results After six months of treatment, BMD in the lumbar spine decreased by 29.5% from baseline. Trabecular bone volume of L2, L3 and L4 vertebrae (pooled) decreased by 31.4% (p< 0.05) and trabecular thickness decreased by 33.9%. Cortical bone thickness decreased by 43.9% (p< 0.05). The average load at which L1 yielded decreased by 67.4%. Static measurements of bone formation decreased by 68.3% and bone resorption increased 10 fold. Kyphoplasty balloon tamps were successfully inflated ex-vivo in vertebral bodies from treated animals.

Discussion Using DXA, cancellous bone histomorphometry and mechanical testing, this study has demonstrated significant trabecular and cortical bone loss in the sheep lumbar spine up to six months after ovariectomy and continuous steroid treatment. These changes are the result of increased resorption and decreased formation of bone. The successful inflation of bone tamps in osteoporotic vertebrae ex-vivo is a prerequisite for in-vivo studies to assess the safety and efficacy of the kyphoplasty procedure.

Introduction: Vertebral compression fractures are common in osteoporosis, resulting in spinal deformities, severe back pain and decreased mobility. Vertebroplasty and kyphoplasty procedures aim to restore the integrity of the deformed vertebral body by injection of biocompatible cement. To date, there have been no long-term studies of the bone-cement interaction in this setting. A reliable large animal model of vertebral osteoporosis would be useful to fully characterise the disease process, to assess potential treatment regimens and to investigate the biocompatibility of bone cements used in kyphoplasty and vertebroplasty. The aim of this pilot study was to develop such a model with ovariectomy, low calcium diet and continuous steroid treatment.

Methods: To induce osteoporosis, ten lactating ewes (mean age 8 years) were ovariectomised, injected weekly with 9 mg dexamethasone (Dexafort, Intervet, Australia) and fed low calcium diet. Weekly serum samples were taken to quantify generalised bone resorption (Type 1 collagen C-telopeptide [CTX], ‚-Cross Laps assay, Roche Diagnostics, Australia). Dual-energy X-ray absorptiometry (DEXA, Hologic QDR 1000+, USA) was used to monitor bone mineral density (BMD) in the lumbar spine (L3-L6) after 0, 2, 4, 6 and 9 months of treatment. At each time interval two sheep were killed by barbiturate injection. The entire lumbar spine (L1-L6) was processed for histology, quantitative histomorphometry, mechanical testing and micro-CT (computed tomography).

Results: CTX levels increased rapidly after two months (p< 0.05). Baseline BMD in the lumbar spine (0.87±0.06 g/cm2) decreased by 16.9±3.8% or 2.72 standard deviations (p< 0.001) after nine months of treatment. Structural parameters of cancellous bone also showed osteoporotic change. Trabecular bone volume of L2, L3 and L6 vertebrae (pooled) progressively decreased from 24.9±1.2% at two months to 16.5±0.47% at nine months (p< 0.05). Trabecular thickness decreased from 0.14±0.01mm to 0.09±0.01mm, (p< 0.05) and trabecular spacing increased from 0.42±0.03mm to 0.47±0.02mm in the same period. The compressive load at which the L1 vertebrae failed decreased by 39.4% after 9 months.

Discussion: This pilot study has demonstrated by DEXA, cancellous bone histomorphometry and mechanical testing, significant bone loss in the sheep lumbar spine up to nine months after ovariectomy and continuous steroid treatment. Assuming that the baseline BMD is representative of mature sheep, the changes in the lumbar spine could be interpreted as osteoporotic. Vertebral bone loss did not reach levels that would result in fracture. However, further work is underway using higher steroid doses to accelerate bone loss. This experimental model will be used to assess aspects of osteoporosis in general and vertebral augmentation procedures in particular.