Long-term results of a prospective study of anterior decompression with fusion and posterior decompression with laminoplasty for treatment of cervical spondylotic myelopathy.

BACKGROUND: There have been no prospective studies comparing anterior surgery and posterior method in terms of long-term outcomes. The purposes of this study is to clarify whether there is any difference in long-term clinical and radiologic outcomes of anterior decompression with fusion (ADF) and laminoplasty (LAMP) for the treatment of cervical spondylotic myelopathy (CSM). METHODS: Ninety-five patients were prospectively treated with ADF or LAMP for CSM in our hospital from 1996 through 2003. On alternate years, patients were enrolled to receive ADF (1997, 1999, 2001, and 2003: ADF group, n = 45) or LAMP (1996, 1998, 2000, and 2002: LAMP group, n = 50). We excluded 19 patients who died during follow-up, and 25 who were lost to follow-up. Clinical outcomes were evaluated by the recovery rate of the Japanese Orthopaedic Association (JOA) score between the two groups. Sagittal alignment of the C2-7 lordotic angle and range of motion (ROM) in flexion and extension on plain X-ray were measured. RESULTS: Mean age at the time of surgery was 58.3 years in the ADF group and 57.9 years in the LAMP group. Mean preoperative JOA score was 10.0 and 10.5, respectively. Mean recovery rate of the JOA score at 3-5 years postoperatively was significantly higher in the ADF group (p < 0.05). Reoperation was required in 1 patient for pseudarthrosis and in 1 patient for recurrence of myelopathy in the ADF group; no patient in the LAMP group underwent a second surgery. There was a significant difference in maintenance of the lordotic angle in the ADF group compared with the LAMP group (p < 0.05), but not in ROM. CONCLUSIONS: Both ADF and LAMP provided similar good outcomes at 10-year time-point whereas ADF could achieve more satisfactory outcomes and better sagittal alignment at the middle-term. However, the incidence of reoperation and complication in the ADF group were higher than those in the LAMP group. STUDY DESIGN: A prospective comparative study (not randomized).

Impact of the surgical treatment for degenerative cervical myelopathy on the preoperative cervical sagittal balance: a review of prospective comparative cohort between anterior decompression with fusion and laminoplasty.

PURPOSE: Cervical sagittal balance has received increased attention as an important determinant of radiological and clinical outcomes. However, no prospective studies have compared the impact of cervical sagittal balance between anterior and posterior surgeries. We previously conducted a prospective study comparing anterior decompression with fusion (ADF) and laminoplasty (LAMP) for degenerative cervical myelopathy (DCM) and reported; however, analysis of cervical alignment within the concept of sagittal balance has yet to be performed, because that concept has recently been proposed. This study aimed to review this prospective cohort, specifically focusing on cervical sagittal balance. METHODS: We prospectively performed ADF or LAMP for DCM patients based on the year of enrollment: ADF was performed in odd-numbered years and LAMP in even-numbered years. Cervical lateral X-ray images taken in the neutral standing position were evaluated preoperatively and at a 1-year follow-up. The radiographic measurements included the following: (1) CL (cervical lordosis: C2-7 lordotic angle), (2) CGH (center of gravity of the head)-C7 SVA (sagittal vertical axis), and (3) C7 slope. The clinical results were evaluated using the Japanese Orthopedic Association scoring system for cervical myelopathy (C-JOA score). RESULTS: We analyzed the data for 66 patients (ADF n = 28, LAMP n = 38). While the CL and CGH-C7 SVA in the ADF were unchanged after the operation, those in the LAMP group worsened, especially in patients with preoperative cervical sagittal imbalance. The C7 slopes were not affected by the operation in either group. The postoperative decreases in the CL in the LAMP group correlated with the preoperative CGH-C7 SVA (r = 0.618, P < 0.01), but those in ADF group did not. In patients with preoperative cervical sagittal imbalance (CGH-C7 SVA ≥40 mm), the recovery rate of the C-JOA score in the ADF group was superior to that in the LAMP group (67.3 vs. 39.8 %). In contrast, for patients without cervical sagittal imbalance, the recovery rate of the C-JOA score showed no significant difference between the ADF and LAMP groups (64.5 vs. 58.7 %). CONCLUSIONS: Postoperative cervical sagittal alignment and balance were maintained after ADF but deteriorated following LAMP, especially in patients with preoperative CGH-C7 SVA ≥40 mm. In these patients, neurological recovery after LAMP was unsatisfactory. LAMP is not suitable for degenerative cervical myelopathy patients with preoperative cervical sagittal imbalance.

Bone Defect Regeneration by a Combination of a ß-Tricalcium Phosphate Scaffold and Bone Marrow Stromal Cells in a Non-Human Primate Model.

BACKGROUND: Reconstruction of large bone defects is a great challenge in orthopedic research. In the present study, we prepared composites of bone marrow-derived stromal cells (BMSCs) and ß-tricalcium phosphate (ß-TCP) with three novel aspects: proliferation of BMSCs with continuous dexamethasone treatment, cell loading under low pressure, and use of autologous plasma as the cell loading medium. The effectiveness of the resulting composite for large bone-defect reconstruction was tested in a non-human primate model, and the bone union capability of the regenerated bones was examined. MATERIALS AND METHODS: Primary surgery: Bone defects (5 cm long) were created in the left femurs of nine cynomolgus monkeys with resection of the periosteum (five cases) or without resection (four cases), and porous ß-TCP blocks were transplanted into the defects. Secondary surgery: Bone marrow aspirates harvested from seven of the nine monkeys were cultured with dexamethasone, and BMSCs were obtained. BMSCs were suspended in autologous plasma and introduced into a porous ß-TCP block under low-pressure conditions. The BMSC/ß-TCP composites were transplanted into bone defects created at the same sites as the primary surgery. Bone union evaluation: Five regenerated femurs were shortened by osteotomy surgery 8 to 15 months after transplantation of the ß-TCP/BMSC composites, and bone union was evaluated radiographically. RESULTS: After the primary surgery and treatment with ß-TCP alone, one of the five periosteum-resected monkeys and two of the four periosteum-preserved monkeys exhibited successful bone reconstruction. In contrast, five of the seven cases treated with the ß-TCP/MSC composite showed successful bone regeneration. In four of the five osteotomy cases, bone union was confirmed. CONCLUSION: We validated the effectiveness of a novel ß-TCP/BMSC composite for large bone defect regeneration and confirmed the bone union capability of the regenerated bone.

What Is the Best Multimodality Combination for Intraoperative Spinal Cord Monitoring of Motor Function? A Multicenter Study by the Monitoring Committee of the Japanese Society for Spine Surgery and Related Research.

Study Design Surgeon survey. Objective To analyze multimodal intraoperative monitoring (MIOM) for different combinations of methods based on the collected data and determine the best combination. Methods A questionnaire was sent to 72 training institutions to analyze and compile data about monitoring that had been conducted during the preceding 5 years to obtain data on the following: (1) types of monitoring; (2) names and number of diseases; (3) conditions of anesthesia; (4) condition of stimulation, the monitored muscle and its number; (5) complications; and (6) preoperative and postoperative manual muscle testing, presence of dysesthesia, and the duration of postoperative motor deficit. Sensitivity and specificity, false-positive rates, and false-negative rates were examined for each type of monitoring, along with the relationship between each type of monitoring and the period of postoperative motor deficit. Results Comparison of the various combinations showed transcranial electrical stimulation motor evoked potential (TcMEP) + cord evoked potential after stimulation to the brain (Br-SCEP) combination had the highest sensitivity (90%). The TcMEP + somatosensory evoked potential (SSEP) and TcMEP + spinal cord evoked potential after stimulation to the spinal cord (Sp-SCEP) combinations each had a sensitivity of 80%, exhibiting little difference between their sensitivity and that obtained when TcMEP alone was used. Meanwhile, the sensitivity was as low as 50% with Br-SCEP + Sp-SCEP (i.e., the cases where TcMEP was not included). Conclusions The best multimodality combination for intraoperative spinal cord monitoring is TcMEP + Br-SCEP, which had the highest sensitivity (90%), the lowest false-positive rate (6.1%), and the lowest false-negative rate (0.2%).

Postoperative Paralysis From Thoracic Ossification of Posterior Longitudinal Ligament Surgery Risk Factor of Neurologic Injury: Nationwide Multiinstitution Survey.

STUDY DESIGN: Retrospective case-control study. OBJECTIVE: The purpose of this study was to examine the factors of postoperative paralysis in patients who have undergone thoracic ossification of posterior longitudinal ligament (OPLL) surgery. SUMMARY OF BACKGROUND DATA: A higher percentage of thoracic OPLL patients experience postoperative aggravation of paralysis than cervical OPLL patients, including patients that presented great difficulties in treatment. However, there were a few reports to prevent paralysis thoracic OPLL. METHODS: The 156 patients who had received thoracic OPLL surgery were selected as the subjects of this study. The items for review were the duration of disease; the preoperative muscle strength (Muscle Manual Testing); OPLL levels (T1/2-4/5: high, T5/6-8/9: middle, and T9/10-11/12: low); the spinal canal occupancy ratio; the ratio of yellow ligament ossification as a complication; the ratio of transcranial-motor evoked potential (Tc-MEP) derivation; the preoperative/postoperative kyphotic angles in the thoracic vertebrae; the correction angle of kyphosis; the duration of surgery; and the amount of bleeding. The subjects were divided into two groups based on the absence or presence of postoperative paralysis to determine the factors of postoperative paralysis. RESULTS: Twenty-three patients (14.7%) exhibited postoperative paralysis. Multivariate analysis identified factors associated with postoperative paralysis: the duration of disease (odds ratio, OR = 3.3); the correction angle of kyphosis (OR = 2.4); and the ratio of Tc-MEP derivation (OR = 2.2). CONCLUSION: The risk factors of postoperative paralysis are a short duration of disease and a small correction angle of kyphosis. In addition, ratios of Tc-MEP derivation below 50% may anticipate paralysis. LEVEL OF EVIDENCE: 4.

Efficacy and safety of porous hydroxyapatite/type 1 collagen composite implantation for bone regeneration: A randomized controlled study.

BACKGROUND: Porous hydroxyapatite/collagen composite (HAp/Col) is a bioresorbable bone substitute composed of nano-scale HAp and porcine type 1 collagen. In this study, the efficacy and safety were assessed in comparison to commercially available porous ß-tricalcium phosphate (ß-TCP). METHODS: Patients with bone defects caused by benign bone tumors, fractures, or harvesting of autografts were randomly allocated for implantation of porous HAp/Col (n = 63) or porous ß-TCP (n = 63). X-ray images were scored and used to evaluate the efficacy of the implantation until 24 weeks after surgery. Blood tests and observation of the surgical site were also performed to evaluate the safety of the implants. In total, 59 and 60 cases were analyzed in the porous HAp/Col and ß-TCP groups, respectively. RESULTS: At 18 and 24 weeks after surgery, the highest grade of bone regeneration was more frequent in the porous HAp/Col group than in the porous ß-TCP group (p = 0.0004 and 0.0254 respectively). Wilcoxon's rank sum test confirmed the superiority of porous HAp/Col from early time points onward (p = 0.0084, 4 w; p = 0.0037, 8 w; p = 0.0030, 12 w; p < 0.0001, 18 w; and p = 0.0316, 24 w). The incidence of adverse effects was higher in the porous HAp/Col group than in the ß-TCP group. However, no serious adverse events were reported and no cases needed to drop out of the clinical trial. CONCLUSIONS: The superiority of porous HAp/Col for bone regeneration in comparison to an established porous ß-TCP was confirmed. Although the incidence of side effects associated with the porous HAp/Col implant was higher than that in the ß-TCP group, no serious adverse events occurred that resulted in rejection of the implants.

Lumbosacral pedicle screw placement using a fluoroscopic pedicle axis view and a cannulated tapping device.

BACKGROUND: Pedicle screw insertions are commonly used for posterior fixation to treat various spine disorders. However, the misplacement of pedicle screws can lead to disastrous complications. Inaccurate pedicle screw placement is relatively common even when placement is performed under fluoroscopic control. In order to improve the accuracy of the screw placement, we applied a technique using guide wires and a cannulated tapping device with the assistance of a fluoroscopic pedicle axis view. METHODS: From 2006 to 2011, 854 pedicle screws were placed in 176 patients in lumbosacral spinal fusion surgeries. The accuracy of screw placement was evaluated using postoperative reconstructed computed tomography images. Screw misplacement was classified as minor (cortical perforation <3 mm), moderate (cortical perforation 3-6 mm), or severe (cortical perforation >6 mm). Using logistic regression analysis, we also investigated the potential risk factors associated with screw misplacement. RESULTS: Pedicle screw misplacement was observed in 37 screws (4.3%) in 34 patients. In the sub-classification analysis, 28 screws (3.3%) were determined to be minor perforations, 7 screws (0.8%) were considered to be moderate perforations, and 2 screws (0.2%) was judged to be a severe perforation (cortical perforation >6 mm). None of the 28 screws that were considered to be minor perforations were associated with any significant symptoms in the patients. However, 2 of the 9 screws that were determined to be moderate or severe perforations caused neurological symptoms (1 of which required revision). No significant differences were observed in the incidence of screw misplacement among the vertebral levels. Significant risk factors for screw misplacement were obesity and degenerative scoliosis. The odds ratios of these significant risk factors were 3.593 (95% confidence interval (CI), 1.061-12.175) for obesity and 8.893 for degenerative scoliosis (95% CI, 1.200-76.220). CONCLUSIONS: A modified fluoroscopic technique using a pedicle axis view and a cannulated tapping instrument can achieve safe and accurate pedicle screw placement. In addition, obesity and degenerative scoliosis were identified as significant risk factors for screw misplacement.

Bone Marrow Stromal Cells Combined With a Honeycomb Collagen Sponge Facilitate Neurite Elongation In Vitro and Neural Restoration in the Hemisected Rat Spinal Cord.

In the last decade, researchers and clinicians have reported that transplantation of bone marrow stromal cells (BMSCs) promotes functional recovery after brain or spinal cord injury (SCI). However, an appropriate scaffold designed for the injured spinal cord is needed to enhance the survival of transplanted BMSCs and to promote nerve regeneration. We previously tested a honeycomb collagen sponge (HC), which when applied to the transected spinal cord allowed bridging of the gap with nerve fibers. In this study, we examined whether the HC implant combined with rat BMSCs increases nerve regeneration in vitro and enhances functional recovery in vivo. We first evaluated the neurite outgrowth of rat dorsal root ganglion (DRG) explants cultured on HC with or without BMSCs in vitro. Regeneration of neurites from the DRGs was increased by BMSCs combined with HC scaffolds. In the in vivo study, 3-mm-long HC scaffolds with or without BMSCs were implanted into the hemisected rat thoracic spinal cord. Four weeks after the procedure, rats implanted with HC scaffolds containing BMSCs displayed better motor and sensory recovery than those implanted with HC scaffolds only. Histologically, more CGRP-positive sensory fibers at the implanted site and 5-HT-positive serotonergic fibers contralateral to the implanted site were observed in spinal cords receiving BMSCs. Furthermore, more rubrospinal neurons projected distally to the HC implant containing BMSCs. Our study indicates that the application of BMSCs in a HC scaffold in the injured spinal cord directly promoted sensory nerve and rubrospinal tract regeneration, thus resulting in functional recovery.

Low-intensity pulsed ultrasound prompts tissue-engineered bone formation after implantation surgery.

BACKGROUND: A practical problem impeding clinical translation is the limited bone formation seen in artificial bone grafts. Low-pressure/vacuum seeding and dynamic culturing in bioreactors have led to a greater penetration into the scaffolds, enhanced production of bone marrow cells, and improved tissue-engineered bone formation. The goal of this study was to promote more extensive bone formation in the composites of porous ceramics and bone marrow stromal cells (BMSCs). METHODS: BMSCs/ß-tricalcium phosphate (ß-TCP) composites were subcultured for 2 weeks and then subcutaneously implanted into syngeneic rats that were split into a low-intensity pulsed ultrasound (LIPUS) treatment group and a control group. These implants were harvested at 5, 10, 25, and 50 days after implantation. The samples were then biomechanically tested and analyzed for alkaline phosphate (ALP) activity and osteocalcin (OCN) content and were also observed by light microscopy. RESULTS: The levels of ALP activity and OCN content in the composites were significantly higher in the LIPUS group than in the control group. Histomorphometric analysis revealed a greater degree of soft tissue repair, increased blood flow, better angiogenesis, and more extensive bone formation in the LIPUS groups than in the controls. No significant difference in the compressive strength was found between the two groups. CONCLUSION: LIPUS treatment appears to enhance bone formation and angiogenesis in the BMSCs/ß-TCP composites.

Intrathecal AAV serotype 9-mediated delivery of shRNA against TRPV1 attenuates thermal hyperalgesia in a mouse model of peripheral nerve injury.

Gene therapy for neuropathic pain requires efficient gene delivery to both central and peripheral nervous systems. We previously showed that an adenoassociated virus serotype 9 (AAV9) vector expressing short-hairpin RNA (shRNA) could suppress target molecule expression in the dorsal root ganglia (DRG) and spinal cord upon intrathecal injection. To evaluate the therapeutic potential of this approach, we constructed an AAV9 vector encoding shRNA against vanilloid receptor 1 (TRPV1), which is an important target gene for acute pain, but its role in chronic neuropathic pain remains unclear. We intrathecally injected it into the subarachnoid space at the upper lumbar spine of mice 3 weeks after spared nerve injury (SNI). Delivered shTRPV1 effectively suppressed mRNA and protein expression of TRPV1 in the DRG and spinal cord, and it attenuated nerve injury-induced thermal allodynia 10-28 days after treatment. Our study provides important evidence for the contribution of TRPV1 to thermal hypersensitivity in neuropathic pain and thus establishes intrathecal AAV9-mediated gene delivery as an investigative and potentially therapeutic platform for the nervous system.

A prospective comparative study of 2 minimally invasive decompression procedures for lumbar spinal canal stenosis: unilateral laminotomy for bilateral decompression (ULBD) versus muscle-preserving interlaminar decompression (MILD).

STUDY DESIGN: A prospective comparative study. OBJECTIVE: To compare prospectively 2 different types of minimally invasive surgery for lumbar spinal canal stenosis (LSCS): unilateral laminotomy for bilateral decompression (ULBD), and muscle-preserving interlaminar decompression (MILD). SUMMARY OF BACKGROUND DATA: Although previous studies have reported several procedures of minimally invasive surgery for the treatment of LSCS, no articles prospectively compared 2 different procedures. METHODS: From 2005 to 2009, we prospectively enrolled 50 patients with LSCS for the treatment with ULBD, and 50 patients for MILD. The patients' symptoms were evaluated using Japanese Orthopedic Association (JOA) score, JOA Back Pain Evaluation Questionnaire, and visual analogue scale before and 2 years after operation. For radiological evaluation, changes in disc height, sagittal translation, and lateral wedging at the decompressed segment, as well as lumbar lordosis were investigated using plain radiographs. RESULTS: Ninety-nine of 100 patients were followed for a minimum of 2 years. No significant differences were found in the recovery rate of JOA score, improvement of JOA Back Pain Evaluation Questionnaire, and changes of the visual analogue scale between the 2 groups. Radiologically, no significant differences were present in the postoperative degenerative changes in disc height, sagittal translation, and lateral wedging. In multilevel surgical procedures; however, clinical scores in low back pain, and lumbar function were significantly greater in the ULBD group than those in the MILD group. The lateral wedging change at L2-L3 and L3-L4 more frequently occurred in the ULBD group than in the MILD group. On the contrary, the number of patients who demonstrated the postoperative sagittal translation at L4-L5 was significantly greater in the MILD group than in the ULBD group. CONCLUSION: Both MILD and ULBD were efficacious procedures for improving neurological symptoms in patients with LSCS. In multilevel decompression surgical procedures, ULBD was superior to MILD in terms of improvement of low back pain and lumbar function at the 2-year time point. LEVEL OF EVIDENCE: 3.

Dynamic changes in spinal cord compression by cervical ossification of the posterior longitudinal ligament evaluated by kinematic computed tomography myelography.

STUDY DESIGN: A prospective clinical study. OBJECTIVE: To investigate the dynamic causative factor in the pathogenesis of myelopathy in patients with cervical ossification of the posterior longitudinal ligament (OPLL) using kinematic computed tomography (CT) myelography. SUMMARY OF BACKGROUND DATA: Kinematic CT myelography is useful for dynamically evaluating the cervical spine with high-resolution images, particularly in bony compressive lesions. However, no studies have evaluated the dynamic factors in patients with OPLL using kinematic CT myelography. METHODS: From 2008 to 2013, 51 consecutive patients with OPLL who presented with myelopathy were prospectively enrolled in this study. The patients were examined with kinematic (flexion-extension) CT myelography using a multidetector CT scanner. The range of motion at C2-C7 from flexion to extension was measured in the sagittal view. The segmental range of motion, anterior-posterior diameter and cross-sectional area (CSA) of the spinal cord were measured at the level where the spinal cord was most compressed by OPLL. RESULTS: The neurological condition of the patients evaluated by Japanese Orthopaedic Association scores were 10.8 ± 2.4 points. The mean range of motion at C2-C7 and at the most compressed segment were 23.1 ± 11.7 and 7.0 ± 4.4°, respectively. Both the anterior-posterior diameter and the CSA at the most compressed levels were significantly decreased during neck extension compared with flexion. Interestingly, the anterior-posterior diameter and the CSA were decreased during neck flexion in 13.7% (7/51) of the patients. All 7 of these patients had massive OPLL with an occupying rate 60% or more. The dynamic change rate of CSA (flexion/extension) was significantly smaller in patients with an OPLL occupying rate 60% or more compared with patients with an occupying rate less than 60%. CONCLUSION: Although spinal cord compression was increased during neck extension in most of the patients, greater levels of compression could be placed on the spinal cord during neck flexion when the patients had OPLL with a high occupying rate. LEVEL OF EVIDENCE: 4.

A new alarm point of transcranial electrical stimulation motor evoked potentials for intraoperative spinal cord monitoring: a prospective multicenter study from the Spinal Cord Monitoring Working Group of the Japanese Society for Spine Surgery and Related Research.

OBJECT: Although multimodal intraoperative spinal cord monitoring provides greater accuracy, transcranial electrical stimulation motor evoked potential (TcMEP) monitoring became the gold standard for intraoperative spinal cord monitoring. However, there is no definite alarm point for TcMEPs because a multicenter study is lacking. Thus, based on their experience with 48 true-positive cases (that is, a decrease in potentials followed by a new neurological motor deficit postoperatively) encountered between 2007 and 2009, the authors set a 70% decrease in amplitude as the alarm point for TcMEPs. METHODS: A total of 959 cases of spinal deformity, spinal cord tumor, and ossification of the posterior longitudinal ligament (OPLL) treated between 2010 and 2012 are included in this prospective multicenter study (18 institutions). These institutions are part of the Japanese Society for Spine Surgery and Related Research monitoring working group and the study group on spinal ligament ossification. The authors prospectively analyzed TcMEP variability and pre- and postoperative motor deficits. A 70% decrease in amplitude was designated as the alarm point. RESULTS: There were only 2 false-negative cases, which occurred during surgery for intramedullary spinal cord tumors. This new alarm criterion provided high sensitivity (95%) and specificity (91%) for intraoperative spinal cord monitoring and favorable accuracy, except in cases of intramedullary spinal cord tumor. CONCLUSIONS: This study is the first prospective multicenter study to investigate the alarm point of TcMEPs. The authors recommend the designation of an alarm point of a 70% decrease in amplitude for routine spinal cord monitoring, particularly during surgery for spinal deformity, OPLL, and extramedullary spinal cord tumor.

After repeated division, bone marrow stromal cells express inhibitory factors with osteogenic capabilities, and EphA5 is a primary candidate.

The differentiation capability of human bone marrow stromal cells (hBMSCs) is thought to deteriorate over multiple doubling processes. To clarify the deterioration mechanisms, the multilineage differentiation capabilities of short- and long-term passaged BMSCs were compared. Predictably, long-term passaged BMSCs showed reduced differentiation capacities compared to short-term passaged cells. Furthermore, a non-human primate heterotopic bone formation model demonstrated that long-term passaged BMSCs have bone formation capabilities but also exert inhibitory effects on bone formation. This finding indicated that long-term passaged BMSCs express higher levels of inhibitory factors than short-term passaged BMSCs do. Co-culture assays of short- and long-term passaged BMSCs suggested that the inhibitory signals required cell-cell contact and would therefore be expressed on the cell membrane. A microarray analysis of BMSCs identified ephrin type-A receptor 5 (EphA5) as an inhibitory factor candidate. Quantitative PCR revealed that among all members of the ephrin and Eph receptor families, only the expression of EphA5 was increased by BMSC proliferation. A gene knockdown analysis using siRNAs demonstrated that knockdown of EphA5 gene expression in long-term passaged BMSCs led to an increase in ALP mRNA expression. These results indicate that EphA5 may be a negative regulator of bone formation. A better understanding of the roles of the ephrin and Eph receptor families in hBMSCs may lead to alternative approaches for manipulating hBMSC fate. In addition, this avenue of discovery may provide new therapeutic targets and quality-control markers of the osteogenic differentiation capabilities of hBMSCs.

Sema3A regulates bone-mass accrual through sensory innervations.

Semaphorin 3A (Sema3A) is a diffusible axonal chemorepellent that has an important role in axon guidance. Previous studies have demonstrated that Sema3a(-/-) mice have multiple developmental defects due to abnormal neuronal innervations. Here we show in mice that Sema3A is abundantly expressed in bone, and cell-based assays showed that Sema3A affected osteoblast differentiation in a cell-autonomous fashion. Accordingly, Sema3a(-/-) mice had a low bone mass due to decreased bone formation. However, osteoblast-specific Sema3A-deficient mice (Sema3acol1(-/-) and Sema3aosx(-/-) mice) had normal bone mass, even though the expression of Sema3A in bone was substantially decreased. In contrast, mice lacking Sema3A in neurons (Sema3asynapsin(-/-) and Sema3anestin(-/-) mice) had low bone mass, similar to Sema3a(-/-) mice, indicating that neuron-derived Sema3A is responsible for the observed bone abnormalities independent of the local effect of Sema3A in bone. Indeed, the number of sensory innervations of trabecular bone was significantly decreased in Sema3asynapsin(-/-) mice, whereas sympathetic innervations of trabecular bone were unchanged. Moreover, ablating sensory nerves decreased bone mass in wild-type mice, whereas it did not reduce the low bone mass in Sema3anestin(-/-) mice further, supporting the essential role of the sensory nervous system in normal bone homeostasis. Finally, neuronal abnormalities in Sema3a(-/-) mice, such as olfactory development, were identified in Sema3asynasin(-/-) mice, demonstrating that neuron-derived Sema3A contributes to the abnormal neural development seen in Sema3a(-/-) mice, and indicating that Sema3A produced in neurons regulates neural development in an autocrine manner. This study demonstrates that Sema3A regulates bone remodelling indirectly by modulating sensory nerve development, but not directly by acting on osteoblasts.

Usefulness of multi-channels in intraoperative spinal cord monitoring: multi-center study by the Monitoring Committee of the Japanese Society for Spine Surgery and Related Research.

OBJECT: The purpose of this study is to analyze the data in terms of the number of channels employed to examine the usefulness of multi-channels in intraoperative spinal cord monitoring. METHODS: The prerequisites for inclusion in the baseline data were as follows: (1) cases in which only CMAP monitoring was conducted; (2) cases in which monitoring was conducted under the same stimulation condition and the recording condition. Cases where inhalation anesthesia was used or muscle relaxants were used as maintenance anesthesia was excluded from the baseline data. Of the 6,887 cases, 884 cases met the criteria. The items examined for each of the different numbers of channels were the sensitivity and specificity, the false positive rate, the false negative rate, and the coverage rate of postoperative motor deficit muscles. RESULT: To examine these two items in terms of the number of channels, the 4-channel group had lower sensitivity and specificity scores compared with the 8- and 16-channel groups (4 channels 73/93 %, 8 channels 100/97 %, 16 channels 100/95 %). Only four channels were derived for these cases and the coverage of postoperative motor deficit muscles was 38 % with only 30 out of the 80 postoperative motor deficit muscles in total being monitored. In the 8-channel group, it was 60 % with 12 of the 20 postoperative motor deficit muscles being monitored. The 16-channel group had 100 % coverage rate of postoperative motor deficit muscles. CONCLUSION: We suggest that multi-channel monitoring of at least eight channels is desirable for intraoperative spinal cord monitoring.

The effects of risedronate administered in combination with a proton pump inhibitor for the treatment of osteoporosis.

This study was performed to investigate the effects of the co-administration of proton pump inhibitor (PPI) on the efficacy of bisphosphonate (BP) treatment for osteoporosis. A total of 180 women with low bone mineral density were randomly divided into four groups, one in which sodium risedronate was administered with sodium rabeprazole and one in which only risedronate was administered (BP + PPI and BP groups, respectively). The biomarkers were measured at the baseline and every 3 months, inlcuding: N-terminal telopeptide of type I collagen corrected for creatinine, bone-specific alkaline phosphatase (BAP), parathyroid hormone, bone mineral density (BMD) of the lumbar spine and physical parameters evaluated according to the SF-36v2™ Health Survey. Statistical comparisons of these parameters were performed after 9 months. Data were available for a total of 137 patients (62 in the BP group and 75 in the BP + PPI group). The Δ % value of increase in BMD and improvement of physical functioning in the BP + PPI group were significantly larger, and its decrease in BAP in the BP + PPI group was significantly smaller than that in the BP group. It is expected that risedronate administration in combination with a PPI may be more effective not only for treating osteoporosis but also improving physical fitness than treatment with risedronate alone.

Porous/dense composite hydroxyapatite for anterior cervical discectomy and fusion.

STUDY DESIGN: A prospective analysis OBJECTIVE: Our aim was to investigate the efficacy of new synthetic porous/dense composite hydroxyapatite (HA) for use in anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: Iliac crest bone graft (ICBG) has been traditionally used as the "gold standard" for ACDF. The significant complication rate associated with harvesting tricortical ICBG, however, has encouraged development of alternative graft substitutes. METHODS: The morphology of the porous/dense HA was observed by scanning electron microscopy (SEM), and the in vitro compressive strength of the composite HA was measured. From April 2005, 51 consecutive patients underwent 81 levels of ACDF using the composite HA with percutaneously harvested trephine bone chips. Clinical and radiological evaluation was performed during the postoperative hospital stay and at follow-up. Furthermore, the outcomes in ACDF using the composite HA were compared with those using tricortical ICBG. RESULTS: The SEM images demonstrated 100- to 300-µm pores (approximately 40% of porosity) in the porous layers of the HA. The compressive strength of the composite HA was 203.1 ± 4.1 MPa. In the clinical study, the demographic data of the patients were similar in HA and ICBG groups. The fusion rates in HA group were comparable with those in ICBG group. The cervical lordosis was enhanced postoperatively in both groups and well preserved at 2-year follow-up without significant differences between the groups. The intraoperative blood loss in HA group was significantly lesser than that in ICBG group. Donor site complications were found in 29.2% of the patients in ICBG group, whereas no donor site morbidity was found in HA group. No major collapse or fragmentation of the composite HA was found. CONCLUSION: The hybrid graft of composite HA and percutaneously harvested trephine chips seemed promising as a graft substitute for ACDF. LEVEL OF EVIDENCE: 4.

Long-term results from use of pasteurized bone.

BACKGROUND: Pasteurized bone (PB) is recycled bone. The pasteurization has a tumor cell-killing effect wit retention of initial strength. However, few reports have been published on its long-term course; thus, in this study, we evaluated the long-term course of use of PB and examined appropriate reconstruction methods. PATIENTS AND METHODS: We reviewed 27 cases in which reconstructive surgery using PB was performed between 1990 and 2002. Of these, we excluded 12 fatal cases and 1 case in which follow-up was discontinued. Therefore, our final analysis consisted of 14 cases with an average follow-up period of 165 months. The reconstruction methods used were: osteoarticular graft in 6 cases, composite graft with prosthesis in 3 cases, intercalary graft in 1 case, and reconstruction using PB from the pelvis in 4 cases. RESULTS: The PB survived in 7 of the 14 cases. Five and 10-year survival of the PB was 78.6 and 47.6%, respectively. Three of the 6 osteoarticular cases failed because of late-onset absorption or infection of the PB. For patients with composite graft or intercalary graft, long-term survival was achieved when small amounts of PB were used. For patients with pelvic grafts, long-term survival was achieved in a case of P1 pelvis, but large PB grafts on small bone-junction surfaces were not successful in the long term. On the basis of these results, we were able to achieve successful long-term results with small PB grafts on large bone-junction surfaces. CONCLUSIONS: To prevent bone absorption and achieve long-term survival of PB, it is important to use a small PB graft and create a large surface area of contact with normal bone. These factors are advantageous to PB survival and to gaining limb function.

Runx2 haploinsufficiency ameliorates the development of ossification of the posterior longitudinal ligament.

Ossification of the Posterior Longitudinal Ligament (OPLL) is a disease that is characterized by the ectopic calcification of the ligament; however, the pathogenesis of OPLL remains to be investigated. We attempted to identify the in vivo role of Runx2, a master regulator of osteoblast differentiation and skeletal mineralization, in the pathogenesis of OPLL. The expression of Runx2 in the ligament was examined using in situ hybridization and immunohistochemistry and by monitoring the activity of a LacZ gene that was inserted into the Runx2 gene locus. To investigate the functional role of Runx2, we studied ENPP1(ttw/ttw) mice, a mouse model of OPLL, that were crossed with heterozygous Runx2 mice to decrease the expression of Runx2, and we performed histological and quantitative radiological analyses using 3D-micro CT. Runx2 was expressed in the ligament of wild-type mice. The induction of Runx2 expression preceded the development of ectopic calcification in the OPLL-like region of the ENPP1(ttw/ttw) mice. Runx2 haploinsufficiency ameliorated the development of ectopic calcification in the ENPP1(ttw/ttw) mice. Collectively, this study demonstrated that Runx2 is expressed in an OPLL-like region, and its elevation is a prerequisite for developing the complete OPLL-like phenotype in a mouse model of OPLL.