Rapid Establishment Of A Rabbit Osteoporosis Model And The Study On The Vertebrae Augmentaion In Osteoporotic Rabbit Vertebrae With Calcium Sulfate/bBMP Composite

BackgroundThe compression fracture in spine is the most complication of osteoporosis. The medical therapies and braces are the primary measures. The surgical measures include internal fixation, vertebroplasty and kyphoplasty. Vertebroplasty is a minimally invasive surgery in spine developed in recent years. It has got good clinical effects in the therapy of benign or malignant lesions and osteoporosis compression fractures in spine. It has become prevalent in minimally invasive surgery of spine for rapidly relieving the back-pain and correcting the deformity. Now, the most commonly used cement is polymethylmethacrylate (PMMA) in vertebroplasty. Unfortunately, PMMA has several potential disadvantages. PMMA is not bioabsorbable and remains permanently in the body. Its unreacted monomer is toxic, and its high polymerization temperature has resulted in temperature readings as much as 1220C. The high compressive strength and stiffness of PMMA causes a biomechanical mismatch between treated and untreated vertebral levels which may increase the risk of adjacent-level fractures. It has been required that the injecting materials can carry medicine for special treatments in clinic. So PMMA can not satisfy these demands. How to explore a biological injecting material,which can not only support the vertebrae but also carry medicine for special treatments, is the object of this experiment.Objective1. To study the approach of rapid establishment of an osteoporosis rabbit model through ovariectomy(OVX) and injecting solu-medrol and to evaluate the micro-architectural and biomechanical changes of cancellous and cortical bone after OVX. To establish a rapid osteoporosis animal model which can meet the requirements of orthopaedic research.2. To evaluate the effects of calcium sulfate cement (CSC) and CSC combined with bovine bone morphogenetic protein (bBMP) on osteoporotic rabbits vertebral micro-architecture, bone mineral density and biomechanical properties in vivo.Material and methodsPart 1 Establishment and evaluation of an osteoporosis rabbit model.20 adult rabbits were randomly divided into six groups: sham-operated group (n=8), OVX-A group (n=4) and OVX-B (n=8) groups. OVX-B group was started to inject solu-medrol for 4 consecutive weeks after 2 weeks late of OVX. Sham group and OVX-A group were control groups. Before and 2 months after the operation, all the rabbits of study underwent dual energy x-ray absorptiometry (DEXA) of the lumbar vertebrae twice. 2 months after the operation, the rabbits were killed. The femoral condyle and shaft underwent DEXA. The trabecular bone(spine and femoral 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. Three-point-bending tests were used to evaluate the mechanical properties of cortical bone (femur shaft).Part 2 the study on the vertebrae augmentaion in osteoporotic rabbit vertebrae with calcium sulfate (CSC) /bBMP composite.60 adult rabbits were randomly divided into five groups: sham-operated group (n=12), C1 group (n=12), C2 group (n=12), C3 group (n=12) and C4 group (n=12). C groups were estabilished osteoporotic rabbit models according to the methods of part 1 experiments. Sham group and C1 group were control groups. 0.1-0.2ml PMMA (Group C2), CSC (Group C3) and CSC/bBMP (Group C4) were injected into L2, L4 and L6 vertebra of every rabbits. 4 rabbits were killed respectively from every group in 24 hours, 6 weeks and 12 weeks after PVP. The trabecular architecture changes were observed histomorphologically. Micro-architecture of vertebrae was measured by micro-CT after the rabbits were killed. 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-A and OVX-B were (266.7±38.58)mg/cm2,(270.1±25.38)mg/cm2 and(272.8±27.08)mg/cm2 respectively. 2 months later, the post-OVX BMD in Sham, OVX-A and OVX-B were ( 281.8±39.22 ) mg/cm2,( 248.9±26.14 ) mg/cm2 and(199.9±30.76)mg/cm2 respectively. BMD in OVX-B decreased by 26.72% compared with the pre-OVX BMD. Histomorphologically, trabecular bone decreased significantly in OVX-B group compared with that in sham group and OVX-B group. Micro-fracture and micro-defect could be seen in OVX-B.The parameters of trabecular bone had significantly difference compared with control groups (p<0.05). In biomechanical testing, the maximum compression strength of vertebrae in OVX-B 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 C3 and C4 was higher than that in C1 group respectively at 6th week and 12th week. The shape of trabecular bone was also better.The architecture of trabecular bone was same as that in sham group. Micro-fractures and micro-defects were also less than that in the C1 groups. After injection of CSC or CSC/bBMP, the Micro-CT reconstruction analysis showed that the BMD in group C3 and C4 were significantly higher than that in group C1 respectively at 6th week and 12th week(P<0.05). The trabecular thickness, connectivity and bone fraction in group C3 and C4 were significantly higher than that in C1 group and were as good as the sham group in 12th week. The results of biomechanical test showed that the maximum compression strength in C4 was higher significantly than that in C1 group in 6th week (P<0.05). It was also higher significantly in both C3 and C4 than that in C1 and had no significantly difference compared with that in sham group and C2 group in 12th week.Conclusion1. Osteoporosis rabbit model can be rapidly establisher by ovariectomy and injecting solu-medrol in 2 months.2. After an osteoporosis rabbit model is induced, the trabecular bone in vertebrae becomes thinning and sparsely. Micro-fractures and micro-defects occur and result in the decrease of biomechanical properties. It is an ideal osteoporosis model for experiments. 3. CSC and CSC/bBMP injecting in osteoporosis vertebrae can repair the micro-fractures and micro-defects in trabecular bone and can enhance the bone quality significantly. CSC and CSC/bBMP can be used as local treatment of vertebral osteoporosis.