Abstract
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.
The abstracts were prepared by Professor Bruce McPhee. Correspondence should be addressed to him at Orthopaedics Division, The University of Queensland, Clinical Sciences Building, Royal Brisbane & Women’s Hospital, Herston, Qld, Australia
