Abstract
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.
The abstracts were prepared by I. B. McPhee. Correspondence should be addressed to the Spine Society of Australia Secretariat, The Adelaide Centre for Spinal Research, Institute of Medical and Veterinary Science, PO Box 14, Rundle Mall, Adelaide SA 5000, Australia.
