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Factors Affecting Small Molecule Trans-Endplate Transport into the Intervertebral Disc In Vivo
Proceedings of the NASS 28th Annual Meeting / The Spine Journal 13 (2013) 1S–168S asset to preoperative planning. This study evaluated the suitability of C2 pedicle screws by using Osirix software to change the gantry angle of CT angiograms in order to measure the anatomic dimensions of the C2 pedicle. PURPOSE: The purpose of this study was to determine whether variable axis interpolation of CT scans would more closely approximate manual anatomic measurements. PATIENT SAMPLE: 47 consecutive trauma patient CT scans. METHODS: Retrospective review of CT angiograms of the head and neck from 47 consecutive trauma patients at our institution. Data collection included length and width of each C2 pedicle from 47 patients, allowing 94 samples, by 3 independent observers. This was performed using Osirix (Pixmeo, Switzerland), a DICOM viewer that allows navigation and visualization in multidimensional imaging, such as 3D, which was utilized here. Vertebral anatomy was also studied to determine if aberrant anatomy would preclude pedicle fixation. Statistical analysis was performed. RESULTS: Of the 47 consecutive CT angiograms reviewed, 20 were of female patients and 27 were male. Overall mean C2 pedicle width and length were 8.27261.364 mm and 27.05263.471 mm, respectively. Gender-specific measurements were also determined. The average width and length of pedicle in females was 8.04061.262 mm and 27.24162.731 mm, respectively. The average width and length of pedicle in males was 8.44461.414 mm and 26.913 63.933 mm, respectively. The gender difference was statistically significant for width (p5.012) but not for length (p50.41). 98% and 97% of pedicles could tolerate a 3.5mm and 4.0 mm screw, respectively, based on width. Only three patients had vertebral anatomy that precluded screw length greater than 14 mm. CONCLUSIONS: Careful preoperative planning is imperative for instrumentation at C2. Fine-cut, noncontrast CT is a useful tool to delineate anatomy; however, the axis of images is not always along the anatomical axis of the vertebra in question. With multidimensional CT or 3D imaging, we found that over 90% of patients could tolerate both 3.5 mm and 4.0 mm pedicle screws at C2. Only 6% of patients (3 of 47) have vertebral anatomy that precludes the use of screw lengths greater than 14 mm. We conclude that the C2 pedicle may be more tolerant of fixation than previously reported, and that variable axis interpolation more close approximates manual anatomic measurement. FDA DEVICE/DRUG STATUS: Cervical pedicle screws (Not approved for this indication). http://dx.doi.org/10.1016/j.spinee.2013.07.146
Thursday, October 10, 2013 4:10 – 5:10 PM Concurrent Session: Disc Biology 98. Factors Affecting Small Molecule Trans-Endplate Transport into the Intervertebral Disc In Vivo Sarah E. Linley1, Josh Peterson1, Rosemarie Mastropolo, BS1, Timothy T. Roberts, MD2, Luciana Lopes, PhD2, James P. Lawrence, MD, MBA3, Jeffrey C. Lotz, PhD4, Eric H. Ledet, PhD1; 1Rensselaer Polytechnic Institute, Troy, NY, US; 2Albany, NY, US; 3Capital Region Spine, Albany, NY, US; 4University of California San Francisco, San Francisco, CA, US BACKGROUND CONTEXT: The intervertebral disc (IVD) is avascular and relies on trans-endplate diffusion from the vasculature and marrow spaces in the adjacent vertebral endplate (EP) to receive nutrients and expel byproducts. In degenerative discs, diffusion is often diminished by
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endplate sclerosis and reduced proteoglycan content. Enhancing diffusion into the disc may act to slow, prevent or reverse degeneration. This can potentially be achieved via pharmaceutical interventions that target and enhance EP vasculature. The calcium channel antagonist nimodipine is a vasodilator and has been shown to increase EP vascularity. Nicotine, a vasoconstrictor, has been linked with IVD degeneration and reduced EP vascularity. PURPOSE: The purpose of this study was to determine how changes to the vertebral EP microvasculature affect diffusion into the IVD in vivo. STUDY DESIGN/SETTING: New Zealand White (NZW) rabbits were administered daily treatments of either nimodipine or nicotine for 8 weeks. Postcontrast enhanced MRI was used to quantify diffusion into the IVD and overall disc health. Histology was used to assess changes to the endplate microvasculature. METHODS: Following IACUC approval, 9 skeletally mature NZW rabbits were randomized to 3 groups of 3 animals each: 8-week daily nimodipine treatment (2.5 mg/kg, subcutaneous injection), 8-week daily nicotine treatment (10.5 mg/24hrs, transdermal patch) and a control group which received no drug treatments. At the conclusion of the treatment regimen, animals were administered the MRI contrast agent gadodiamide intravenously and then euthanized 10 minutes later. The lumbar spines were harvested and imaged using postcontrast enhanced 7T MRI. T1 and T2 constants were quantified in the nucleus pulposus (NP) as measures of diffusion and disc health, respectively. Lumbar motion segments were routinely processed for histology, and the red blood cells in the microvasculature stained via rapid Heidendain stain. Serial images were obtained of the subchondral bone adjacent to the NP at 20X magnification to quantify vessel number and vessel area, as well as vessel distance from the cartilage EP. Statistical differences between groups were assessed using an ANVOA with Fisher’s Post-Hoc test. RESULTS: MRI analysis demonstrated a significant 8.4% increase in diffusion into the NP in the nimodipine group as compared to controls. No difference was detectable between nicotine and control groups with respect to diffusion. T2 mapping demonstrated a mean 18.2% decrease in T2 constant in the nicotine group as compared to control, consistent with early stage degeneration. Interestingly, vessel number was significantly increased by 34% in the nicotine group relative to control. Total vessel area was significantly increased by 37% and 57% for nimodipine and nicotine groups, respectively, relative to control. Mean vessel distance from the EP was significantly increased by 21% in the nicotine group compared to control. CONCLUSIONS: Transport into the IVD is complex and can be influenced by many factors. Despite an increase in vessel number and area in the nicotine treated group, we did not observe an increase in diffusion into the NP. This may have been due to the increased distance of vessels from the cartilage EP, or due to degenerative changes to the IVD induced directly by nicotine. Conversely, nimodipine showed an increase in diffusion via increased vessel area, but no increase in vessel number was observed relative to controls. Our results suggest that drugs which selectively target the endplate microvasculature can enhance transport into the disc and potentially slow, prevent or reverse degeneration. FDA DEVICE/DRUG STATUS: nimodipine (Not approved for this indication) http://dx.doi.org/10.1016/j.spinee.2013.07.148
99. Effects of Type-2 Diabetes Mellitus on Intervertebral Disc Health in Rats Lionel N. Metz, MD1, Aaron J. Fields, PhD1, Alberto F. Lovell, BS2, Britta Berg-Johansen3, Morsi Khashan, MD4, James Graham, BS5, Peter Havel, DVM, PhD5, Jeffrey C. Lotz, PhD1; 1University of California San Francisco, San Francisco, CA, US; 2Hayward, CA, US; 3Berkeley, CA,
Refer to onsite Annual Meeting presentations and postmeeting proceedings for possible referenced figures and tables. Authors are responsible for accurately reporting disclosures and FDA device/drug status at time of abstract submission.
Thursday, October 10, 2013 4:10 – 5:10 PM Concurrent Session: Disc Biology 98. Factors Affecting Small Molecule Trans-Endplate Transport into the Intervertebral Disc In Vivo Sarah E. Linley1, Josh Peterson1, Rosemarie Mastropolo, BS1, Timothy T. Roberts, MD2, Luciana Lopes, PhD2, James P. Lawrence, MD, MBA3, Jeffrey C. Lotz, PhD4, Eric H. Ledet, PhD1; 1Rensselaer Polytechnic Institute, Troy, NY, US; 2Albany, NY, US; 3Capital Region Spine, Albany, NY, US; 4University of California San Francisco, San Francisco, CA, US BACKGROUND CONTEXT: The intervertebral disc (IVD) is avascular and relies on trans-endplate diffusion from the vasculature and marrow spaces in the adjacent vertebral endplate (EP) to receive nutrients and expel byproducts. In degenerative discs, diffusion is often diminished by
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endplate sclerosis and reduced proteoglycan content. Enhancing diffusion into the disc may act to slow, prevent or reverse degeneration. This can potentially be achieved via pharmaceutical interventions that target and enhance EP vasculature. The calcium channel antagonist nimodipine is a vasodilator and has been shown to increase EP vascularity. Nicotine, a vasoconstrictor, has been linked with IVD degeneration and reduced EP vascularity. PURPOSE: The purpose of this study was to determine how changes to the vertebral EP microvasculature affect diffusion into the IVD in vivo. STUDY DESIGN/SETTING: New Zealand White (NZW) rabbits were administered daily treatments of either nimodipine or nicotine for 8 weeks. Postcontrast enhanced MRI was used to quantify diffusion into the IVD and overall disc health. Histology was used to assess changes to the endplate microvasculature. METHODS: Following IACUC approval, 9 skeletally mature NZW rabbits were randomized to 3 groups of 3 animals each: 8-week daily nimodipine treatment (2.5 mg/kg, subcutaneous injection), 8-week daily nicotine treatment (10.5 mg/24hrs, transdermal patch) and a control group which received no drug treatments. At the conclusion of the treatment regimen, animals were administered the MRI contrast agent gadodiamide intravenously and then euthanized 10 minutes later. The lumbar spines were harvested and imaged using postcontrast enhanced 7T MRI. T1 and T2 constants were quantified in the nucleus pulposus (NP) as measures of diffusion and disc health, respectively. Lumbar motion segments were routinely processed for histology, and the red blood cells in the microvasculature stained via rapid Heidendain stain. Serial images were obtained of the subchondral bone adjacent to the NP at 20X magnification to quantify vessel number and vessel area, as well as vessel distance from the cartilage EP. Statistical differences between groups were assessed using an ANVOA with Fisher’s Post-Hoc test. RESULTS: MRI analysis demonstrated a significant 8.4% increase in diffusion into the NP in the nimodipine group as compared to controls. No difference was detectable between nicotine and control groups with respect to diffusion. T2 mapping demonstrated a mean 18.2% decrease in T2 constant in the nicotine group as compared to control, consistent with early stage degeneration. Interestingly, vessel number was significantly increased by 34% in the nicotine group relative to control. Total vessel area was significantly increased by 37% and 57% for nimodipine and nicotine groups, respectively, relative to control. Mean vessel distance from the EP was significantly increased by 21% in the nicotine group compared to control. CONCLUSIONS: Transport into the IVD is complex and can be influenced by many factors. Despite an increase in vessel number and area in the nicotine treated group, we did not observe an increase in diffusion into the NP. This may have been due to the increased distance of vessels from the cartilage EP, or due to degenerative changes to the IVD induced directly by nicotine. Conversely, nimodipine showed an increase in diffusion via increased vessel area, but no increase in vessel number was observed relative to controls. Our results suggest that drugs which selectively target the endplate microvasculature can enhance transport into the disc and potentially slow, prevent or reverse degeneration. FDA DEVICE/DRUG STATUS: nimodipine (Not approved for this indication) http://dx.doi.org/10.1016/j.spinee.2013.07.148
99. Effects of Type-2 Diabetes Mellitus on Intervertebral Disc Health in Rats Lionel N. Metz, MD1, Aaron J. Fields, PhD1, Alberto F. Lovell, BS2, Britta Berg-Johansen3, Morsi Khashan, MD4, James Graham, BS5, Peter Havel, DVM, PhD5, Jeffrey C. Lotz, PhD1; 1University of California San Francisco, San Francisco, CA, US; 2Hayward, CA, US; 3Berkeley, CA,
Refer to onsite Annual Meeting presentations and postmeeting proceedings for possible referenced figures and tables. Authors are responsible for accurately reporting disclosures and FDA device/drug status at time of abstract submission.