| BackgroundOsteoporosis/osteopenia is now becoming much more prevelent than ever and spinal osteoporosis is more frequent in the elderly. For the compression fractures in spine, medical therapies and braces are the primary measures. Vertebroplasty and kyphoplasty can also relieve backpain and correct the deformities. However, for the un-fractured, high-risk spines, surgical treatments seem like unsuitable. Time-consuming treatments, such as medication and braces, can not increase the bone strength quickly. Compression fractures often occur during treatment. Thus, how to improve the bone quality in short term and avoid compression fractures has been an important clinical problem. Besides that, for the osteoporotic elderly patients who need internal fixation surgical treatment, the speed of bone loss resulting from bed-rest would be greater than that of bone remodeling which is gain from medical therapies. As a result, bone quality would deteriorate and the risk of internal fixation failure would increase. How to deal with the high-risk vertebrae during the operation has been another clinical problem which needs to be solved.Objective1. To study the exact time to establishment of an osteoporosis ovine model through ovariectomy (OVX) and to evaluate the micro-architectural and biomechanical changes of cancellous and cortical bone after OVX. To establish an osteoporosis animal model which could meet the requirements of orthopaedic research.2. To compare the correlationship between BMD, micro-architectural parameters and biomechanical properties, and find better predictable indices for mechanical properties of cancellous bone.3. To evaluate the effects of bovine bone morphogenetic protein (bBMP) combined with fibrin sealant (FS) on osteoporotic ovine vertebral micro-architecture, bone mineral density and biomechanical properties in vivo.Material and methodsPart 1 Establishment of an osteoporosis ovine model20 adult sheep were randomly divided into three groups: sham-operated group(n=8), OVX-1 group(n=4) and OVX-2 group(n=8). At the time of operation, all sheep underwent dual energy x-ray absorptiometry (DEXA) of the lumbar vertebrae. 12 months after operation, all sheep were sacrificed and underwent DEXA scan for lumbar spine. The trabecular bone (spine, femoral neck and condyle) and cortical bone (femoral shaft) were harvested and reconstructed by micro-CT. Compressive mechanical properties of cancellous bone were determined from biopsies of vertebral bodies and femoral condyles. Three-point-bending tests were used to evaluate the mechanical properties of cortical bone (femur shaft).Part 2 Evaluation of the treatment effects of bovine BMP combined with fibrin sealant on osteoporotic spine in ovine model: an in vivo studySix sheep were ovariectomized (OVX) for one year. All sheep underwent BMD scan at the time of OVX. After one year of low-calcium diet, the BMD of lumbar spine was measured again to ensure the eatablishment of osteoporosis animal model. According to the ladin square design, 20mg bBMP/fibrin sealant (FS) (Group A), 20mg bBMP (Group B) and FS (Group C) were injected into L4,L5,L6 vertebra respectively. The trabecular architecture changes were observed histomorphologically. The BMD and micro-architecture of vertebrae were measured by dural energy X-ray absorption meter and micro-CT three months later. Axial compression tests were carried out on vertebral specimens to evaluate their strength.ResultPart 1: The pre-OVX BMD for lumbar spine in Sham, OVX-1 and OVX-2 were (1.15±0.09)g/cm2, (1.26±0.08)g/cm2 and (1.11±0.10)g/cm2 respectively. 5 months later, the post-OVX BMD in OVX-1 was (1.28±0.06)g/cm2. 12 months later, BMD in Sham and OVX-2 were (1.22±0.07)g/cm2 and (0.86±0.09)g/cm2. BMD in OVX-2 decreased by 29.5% compared with that in Sham group. Histomorphologically, trabecular bone decreased significantly in OVX-2 group compared with that in control groups. Micro-fracture and micro-defect could be seen in OVX-2. The BS/BV, Tb.Th and Tb.N decreased significantly, while the Tb.N and BVF increased (P<0.01). In biomechanical testing, the maximum compressing strength of trabecular bone in OVX-2 was lower than that in the other two groups. In 3-point bending test, there was no difference between three groups.Part 2: Histomorphologically, the connectivity in group A was higher than that in control groups. The shape of trabecular bone were better. Micro-fractures and micro-defects were also less than the control groups. After injection of BMP/FS, the BMD in group A (1.334 g/cm2) was significantly higher than in group B (1.139 g/cm2) and group C (1.163 g/cm2). The MicroCT reconstruction analysis also showed that the trabecular thickness, connectivity and bone fraction in group A were significantly higher than in control groups. The trabecular separation and BS/BV were lower (P<0.05). The results of biomechanical test showed that the maxium compression strength, the maxium compression strain, engery absorbtion and modulas were significantly higher than those in the control groups. The correlation between micro-architectural parameters and mechanical index is higher than BMD gained from DEXA.Conclusion1. Ovariectomy can establish post-menopausal osteoporosis ovine model, but the ovariectomized phase should be maintained 12 months at least to ensure the animal model could be established successfully. However, the BMD and biomechanical characters of ovine cortical bone do not decrease significantly 12 months after ovariectomy..2. After an osteoporosis ovine model is induced, the trabecular bone in vertebrae becomes thinning and sparsely. Micro-fractures and micro-defects occure and result in the decrease of biomechanical properties.3. The correlation between micro-architectural parameters and mechanical index can be used as better predictable indices for mechanical properties of cancellous bone.4. bBMP/FS can repair the micro-fractures and micro-defects in trabecular bone and can enhance the bone density and bone quality significantly. bBMP/FS can be used as local treatment of vertebral osteoporosis.
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