ABSTRACT
BACKGROUND: Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been widely used on clinic; however, there are still few reports addressing rhBMP-2-induced osteogenesis in intervertebral disc.OBJECTIVE: To verify the effect of rhBMP-2 to induce interbody fusion in rabbits.DESIGN, TIME AND SETTING: Randomized controlled animal study and multi-level evaluation, which was performed in Affiliated Hospital of Medical College of Qingdao University from February to July 2007.MATERIALS: 24 adult New-Zealand rabbits weighing 3.5-4.5 kg were used to expose L4-5 and L5-6 intervertebral disc; rhBMP-2 (1 mg/ampoule, purity≥95%) was provided by Beijing Bailingke Biological Products Co., Ltd.METHODS: 24 rabbits were randomly divided into experimental group and control group with 12 rabbits for each. In the experimental group, saline (20 μL, containing 200 μg rhBMP-2) was injected into nucleus pulposus of L4-5 intervertebral disc; equivalent saline was inserted into nucleus pulposus of L5-6 intervertebral disc as controls. Rabbits in the control group were injected with saline (20 μL) into nucleus pulposus of L4-5 intervertebral disc.MAIN OUTCOME MEASURES: Morphological changes of injected segments were observed by hand-feeling check together with histological and imaging tests at 10, 30, 60, and 90 days postoperatively.RESULTS: 24 rabbits were included in the final analysis. ①In the experimental group, the motion range of L4-5 segment was not limited at 10 days postoperatively, and lightly limited at 30 days, but severely limited at 60 days postoperatively; L4-5 segment was fixed tightly at 90 days postoperatively. Moreover, motion range of L5-6,segment and articular motion range in the control group were not changed remarkably. ② L4-5 interbedy space was narrowed at 10 days or even disappeared at 90 days postoperatively, and then osteogenesis fusion was formed. Transmittance of intervertebral space in the L5-6 segment and in the control group was not changed obviously. ③ Nucleus pulposus was gradually shrunk at 10 days postoperatively; partial cartilage endplate transformed into mature woven bone, and collagen fiber structure of annulus fibrosus gradually disappeared at 90 days postoperatively. A lot of mesenchymal cells were aggregated surrounding annulus fibrosus at 10 and 30 days postoperatively. Moreover, mature woven bone was formed in annulus fibrosus near to cartilage endplate at 90 days postoperatively. However, histological and morphological changes were not found in the control group at those four time points.CONCLUSION: rhBMP-2 can induce intervertebral disc osteogenesis so as to achieve interbody fusion.