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Vertebral Cartilage Endplate Lesions:a Morphological Study to Evaluate the Effects of Osteoporosis and Disc Degeneration in Rats
|School||Southern Medical University,|
|Keywords||osteoporosis disc degeneration cartilage endplate lesion rat|
BackgroundsOsteoporosis and ration' dissertation">disc degeneration are both common causes which always make the elder suffered physically and mentally. Both diseases can cause pain and immobility, lower the quality of life and increas disability and mortality. Osteoporosis is a disease that characterized by decreased bone mass and progressive erosion of the microstructure. As a result of sever osteopororsis, key skeletalsites such as the hip, spine and wrists are at increased risk of fracture at low energy impact, such as a fall. In our coutury, there are about84million people with osteoporosis which accouts for6.6%of the total population. Osteoporosis is common in senior women. The incidence of facture as a result of osteoporosis in postmenopausal women is30%at the age of50-59years old,70%at the age of60-70years old and up to80%over the age of75years old. It would seriously compromise the life quality. Disc degeneration, another age-related disease, is an initiating factor of spinal degeneration. The intervertebral disc, the largest avascular tissue in the body, is comprised of a centrally located nucleus pulposus (NP) core, the peripherally located multilaminar annulus fibrosus (AF), and cartilaginous endplates. There are many casuses for the disc degeneration, such as overloading, inflammatory factors and the degeneration of the endplate, et al. Lesion of the cartilage endplate blocks nutrient supply to the disc and leads to the disc degeneration.Osteoporosis and intervertebral disc degeneration may coexist in spine. Osteoprosis can cause the loosening of internal fixation. Spinal degeneration is one kind of osteoarthritis. Even though an inverse relationship between osteoporosis and osteoarthritis in peripheral joints has been reported in literatures, such relationship in the spine remains controversial. Some studies found that disc degeneration is common seen with high BMD of the veterbral body. But the other studies, particularly from the animal studies, found that osteoporosis could induce the disc degeneration and contribute to the endplate lesion.The intervertebral disc is the largest avascular tissue in the body. The vertebral endplate, a thin structure adjacent to the disc and a major pathway of nutrient supply to the disc, changes with the disc degeneration. Vertebral cartilage endplate are similar to hyaline cartilage but hydrated less than the hip or knee cartilage, and becomes thinner and calcified when aged. Cadaveric studies found that endplate lesions were associated with the disc degeneration with a clear dosage effect. The animal model confirmed the disc degeneration always happened with the lesion of cartilage endplate. The vertebral cartilage endplate is sensitive to the mechanical loading. The abnormal stresss could cause the decrease of the chondrocytes and accelerate the calcification. Osteoporosis leads to the deterioration of bone in whole, but actually increased bone mineral density of vertebral cartilage endplate. Therefore, osteoporosis would accelerate the lesion and the calcification of the cartilage endplates, and result in the disc degeneration. There is a complex and dynamic relationship between disc degeneration and osteoporosis. We can not get a clear conclusion with clinical data only. There is a need to set up a new animal model which combined disc degeneration and osteoporosis together to understand the relationship and to investigate the effects of disc degeneration compounded with osteoporosis on the cartilage endplate.Objectives1. To evaluate the cartilage endplate lesions at different cervical spine levels, intervertebral disc height and histological scores for disc degeneration in the rats model of cervical intervertebral disc degeneration due to imbalance of dynamic and static forces.2. A new animal model combined the disc degeneration and osteoporosis will be established to evaluate the compounding effect of disc degeneration and osteoporosis on the cartilage endplate and to determine whether osteoporosis could induce and acclelerate the disc degeneration.Methods1. Twenty-four Sprague-Dawley female rats at the age of3months were assigned randomly into the model and control groups (n=14and10). The posterior muscles along the cervical spine were sectioned in the model group. The C4～C7segments were harvested at12,18and24weeks after surgery. Specimens were scanned using micro CT, and stained with Safranine O/fast green. Lesions of the cartilage endplate were identified on axial CT images, and ratio of the lesion area to the whole endplate area was calculated. Intervertebral disc height (IDH) was measured and, and disc degeneration (DD) was graded for each sample.2. Fifty-two Sprague-Dawley female rats were assigned randomly into CMS+OVX, CMS, OVX and Sham groups (n=14,14,14and10), respectively. Each rat was underwent "real" or "control" OVX and CMS surgery under the same anesthesia procedure. The CMS surgery, adopted from a previous study (19), required the section of the paraspinal musculature and posterior cervical spinal ligaments from C2to C7. Such surgical intervention resulted in cervical spine instability and secondary intervertebral disc degeneration. The OVX surgery was a bilateral ovariectomy and commonly used for producing postmenopausal osteoporosis in female rats.The C6/C7segment and tibia were harvested at12,18and24weeks after surgery. Specimens were scanned using micro CT, and then stained with Safranine O/fast green. Structural indices of C6body and tibial metaphyseal region were evaluated. Cartilage endplate lesions were identified on axial CT images, and the lesion areas calculated. Intervertebral disc height (IDH) was measured, and DD was graded for each specimen.Results1. The cartilage endplate lesion was on the ventral cartilage endplates with greater lesion for the lower levels at12weeks after surgery in the model group. The severer lesion in the C5/C6and C6/C7was seen in the model group comparing to the control group at18and24weeks after surgery (P<0.05). The lesion varied with levels. The lesion in C6/C7was severer than the lesion in C4/C5(P<0.05). The histological results showed that the lesion shrunk and calcified in situ since18and24weeks. Compared to the control group, the IDH were lower for the C5/C6and C6/C7in the model group at12weeks. The DD scores for the model group were11.5±1.0,11.8±1.0and12.8±0.8at the C4/C5, C5/C6and C6/C7levels, respectively. DD scores changed significantly among levels. The C6/C7DD scores were greater than the scores of other levels (P<0.05). The lesion correlated to DD scores at12,18and24weeks (P<0.05), and IDH at18and24weeks (P<0.05), respectively.2. OP occurred at12weeks after the OVX surgery and became severe afterwards. The lesion was on the ventral cartilage endplates with the greatest lesion at12weeks after CMS surgery, and was severe with OVX added surgery (28%, P<0.05) and for the C6caudal endplate, respectively. The lesion was shrunk and calcified in situ at18and24weeks. The CMS surgery resulted in significant decrease of IDH, while the OVX added surgery led to IDH decreasing significantly at24weeks (P<0.05). Histological DD scores were higher following CMS or OVX surgery. DD scores correlated to the lesion and IDH (P<0.01). Our results suggested that DD induced cartilage endplate lesion while OP appeared to deteriorate the lesion. The cartilage endplate was worn off at the early stage and calcified in situ later. The lesion and IDH were correlated with the DD levels. The results imply that osteoporosis may accelerate the disc degeneration at specific time.Conclusions1. Our results suggested that the dynamic-static-force-imbalance rat model generated obvious disc degeneration at the C6/C7level with larger cartilage endplate lesion, lower IDH and higher DD scores when compared to the C4/C5and C5/C6levels. The cartilage endplate lesion was associated with IDH and DD scores.2. Disc degeneration induced cartilage endplate lesion while osteoporosis appeared to deteriorate the lesion more to the degenerating discs. The cartilage endplate lesion may be related to cartilage endplate wearing off at the early stage and calcification in situ later. The lesion and intervertebral disc height were associated with the disc degeneration levels. Our results imply that osteoporosis may accelerate the disc degeneration at specific time.