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Ligamentum flavum (LF) hypertrophy is a major cause of lumbar spinal canal stenosis. Although mechanical stress is thought to be a major factor involved in LF hypertrophy, the exact mechanism by which it causes hypertrophy has not yet been fully elucidated. Here, changes in gene expression due to long-term mechanical stress were analyzed using RNA-seq in a rabbit LF hypertrophy model. In combination with previously reported analysis results, periostin was identified as a molecule whose expression fluctuates due to mechanical stress. The expression and function of periostin were further investigated using human LF tissues and primary LF cell cultures. Periostin was abundantly expressed in human hypertrophied LF tissues, and periostin gene expression was significantly correlated with LF thickness. In vitro, mechanical stress increased gene expressions of periostin, transforming growth factor-β1, α-smooth muscle actin, collagen type 1 alpha 1, and interleukin-6 (IL-6) in LF cells. Periostin blockade suppressed the mechanical stress-induced gene expression of IL-6 while periostin treatment increased IL-6 gene expression. Our results suggest that periostin is upregulated by mechanical stress and promotes inflammation by upregulating IL-6 expression, which leads to LF degeneration and hypertrophy. Periostin may be a pivotal molecule for LF hypertrophy and a promising therapeutic target for lumbar spinal stenosis.

Background Context Accurate diagnosis of osteoporotic vertebral fracture (OVF) is important for improving treatment outcomes; however, the gold standard has not been established yet. A deep-learning approach based on convolutional neural network (CNN) has attracted attention in the medical imaging field. Purpose To construct a CNN to detect fresh OVF on magnetic resonance (MR) images. Study Design/Setting Retrospective analysis of MR images Patient Sample This retrospective study included 814 patients with fresh OVF. For CNN training and validation, 1624 slices of T1-weighted MR image were obtained and used. Outcome Measure We plotted the receiver operating characteristic (ROC) curve and calculated the area under the curve (AUC) in order to evaluate the performance of the CNN. Consequently, the sensitivity, specificity, and accuracy of the diagnosis by CNN and that of the two spine surgeons were compared. Methods We constructed an optimal model using ensemble method by combining nine types of CNNs to detect fresh OVFs. Furthermore, two spine surgeons independently evaluated 100 vertebrae, which were randomly extracted from test data. Results The ensemble method using VGG16, VGG19, DenseNet201, and ResNet50 was the combination with the highest AUC of ROC curves. The AUC was 0.949. The evaluation metrics of the diagnosis (CNN/surgeon 1/surgeon 2) for 100 vertebrae were as follows: sensitivity: 88.1%/88.1%/100%; specificity: 87.9%/86.2%/65.5%; accuracy: 88.0%/87.0%/80.0%. Conclusions In detecting fresh OVF using MR images, the performance of the CNN was comparable to that of two spine surgeons.

Recently, an expandable cage equipped with rectangular footplates has been used for anterior vertebral replacement in osteoporotic vertebral fracture (OVF). However, the postoperative changes in global alignment have not been elucidated. The purpose of this study was to evaluate local and global spinal alignment after anterior and posterior spinal fixation (APSF) using an expandable cage in elderly OVF patients. This retrospective multicenter review assessed 54 consecutive patients who underwent APSF for OVF. Clinical outcomes were compared between postoperative sagittal vertical axis (SVA) &gt, 95 mm and ≤95 mm groups to investigate the impact of malalignment. SVA improved by only 18.7 mm (from 111.8 mm to 93.1 mm). VAS score of back pain at final follow-up was significantly higher in patients with SVA &gt, 95 mm than SVA ≤ 95 mm (42.4 vs. 22.6, p = 0.007). Adjacent vertebral fracture after surgery was significantly more frequent in the SVA &gt, 95 mm (37% vs. 11%, p = 0.038). Multiple logistic regression showed significantly increased OR for developing adjacent vertebral fracture (OR = 4.76, 95% CI 1.10–20.58). APSF using the newly developed cage improves local kyphotic angle but not SVA. The main cause for the spinal malalignment after surgery was postoperative development of adjacent vertebral fractures.

Background: Anterior and posterior spinal fixation (APSF) can provide rigid structural anterior column support in patients with osteoporotic vertebral fracture (OVF). A new rectangular footplate designed based on biomechanical studies of endplates provides better resistance to subsidence. However, differences in characteristics exist between the thoracolumbar and lower lumbar spine. The purpose of this study was to evaluate the surgical outcomes following APSF using an expandable cage with rectangular footplates in the thoracolumbar/lumbar region. Methods: Consecutive patients who underwent APSF for OVF at multiple centers were retrospectively reviewed. Clinical and radiographic evaluations were performed by dividing the patients into thoracolumbar (TL, T10–L2) and lumbar (L, L3–L5) groups. Surgical indications were incomplete neurologic deficit or intractable back pain with segmental spinal instability. Surgical outcomes including the Japanese Orthopaedic Association (JOA) score and reoperation rate were compared between TL and L groups. Results: Sixty-nine patients were followed-up for more than 12 months and analyzed. Operative intervention was required for 35 patients in the TL group and 34 patients in the L group. Mean ages in the TL and L groups were 76.5 years and 75.1 years, respectively. Intra-vertebral instability was more frequent in the TL group (p

OBJECTIVE The authors aimed to determine the efficacy of open-door laminoplasty with stand-alone autologous bone spacer for preserving enlarged lamina in patients with cervical myelopathy. METHODS Patients who underwent open-door laminoplasty for cervical myelopathy with stand-alone autologous bone spacer and underwent CT 1 week and 1 year after surgery were included in this study. There were 20 men and 13 women, with an average (range) age of 65.0 (37–86) years. Seventeen patients were younger than 70 years, and 16 patients were older than 70 years. Autogenous bone spacers made from spinous processes were used in all patients. Slits were made on both sides of the spacers. The lamina was raised with a curette, and a spacer was inserted without any sutures. Before surgery and 1 week and 1 year after surgery, the anteroposterior diameter (APD) of the spinal canal was measured using midsagittal-plane CT–multiplanar reconstruction. The bone union rate of the hinge side and autogenous bone spacer of each lamina was determined using CT images obtained 1 year after surgery. Results 1 year after surgery were evaluated using Japanese Orthopaedic Association (JOA) score. RESULTS The mean ± SD APD increase rate was 56.3% ± 21.3% 1 week after surgery and 51.7% ± 20.6% 1 year later. The average APD decrease rate was 2.9% ± 3.8%. The bone union rate on the hinge side was 100%, and that of autologous bone spacer was 93.8% 1 year after surgery. The mean APD decrease rate was 3.3% in patients younger than 70 years and 2.3% in those older than 70 years. There was no significant difference between the two groups (p > 0.05, nonpaired t-test). The JOA score averaged 10.1 before surgery and 13.3 a year after surgery (total score 17). The average improvement rate was 46.3% ± 26.4%. CONCLUSIONS The authors devised and implemented a technique for inserting an autologous bone spacer between the opened lamina and lateral mass without sutures. The enlarged spinal canal was maintained 1 year after surgery. This simple method does not require any instrumentation or additional cost to stabilize the opened lamina.

The main concern with revision lumbar surgery is the possibility of neurologic complications. This retrospective study was conducted to clarify the risk factors, especially the effects of nerve stretching, for postoperative neurologic complications in posterior lumbar interbody fusion (PLIF) without excessive nerve retraction by bilateral total facetectomy as revision surgery.Between 2005 and 2015, 50 consecutive patients underwent revision PLIF for recurrent stenosis or recurrent disc herniation. The patients were divided into two groups: patients with neurological complications (NC group) and patients without neurological complications (non-NC group). Radiological examinations to evaluate the magnitude of nerve stretching included the following pre- and postoperative plain radiograph measurements: anterolisthesis at flexion, intervertebral lordosis in the neutral position, and posterior disc height in the neutral position.Sixteen patients (32%) had neurological complications. The decrease in intervertebral lordosis was significantly greater in the NC group than that in the non-NC group (0.8° vs. -1.5°, P0.05). Distraction of the posterior disc height was significantly greater in the NC group than that in the non-NC group (5.0 mm vs. 2.6 mm, P0.01). Neurological complications were seen in all patients with a decrease in intervertebral lordosis3° and distraction of the posterior disc height3 mm.Decreased intervertebral lordosis, and distraction of the posterior disc height, which can be controlled by surgeons, appear to be risk factors for neurological complications following revision PLIF. In revision PLIF, surgeons should create segmental lordosis without excessive disc height distraction.

Study Design: A retrospective study. Objectives: To investigate surgical outcomes and limitations of decompression surgery for degenerative spondylolisthesis. Methods: One hundred patients with degenerative spondylolisthesis who underwent decompression surgery alone were included in this study. The average follow-up period was 3.7 years. Radiography and magnetic resonance imaging were used for radiological assessment. Patients with a recovery rate of >50% throughout the study period were classified as the control group (Group C), while those with a recovery rate of Results: Patient distribution in each group was 73, 12, 7, and 8 in Groups C, P, E, and T, respectively. As for preoperative radiological features, slippage and an upper migrated disc in Group P, disc wedging and an upper migrated disc in Group E, and lamina inclination and posterior opening in Group T were evident. The cutoff value of preoperative slippage with a poor outcome was 13%. Conclusions: Surgical outcomes of decompression surgery for degenerative spondylolisthesis were successful in 73% cases. Preoperative radiological features for poor outcomes were slippage of more than 13%, an upper migrated disc, disc wedging, and lamina inclination.

Study Design: Retrospective study. Objective: There have been few reports of adjacent segment disease (ASD) after posterior lumbar interbody fusion (PLIF) with large numbers and long follow-up. The purpose of this study was to investigate (1) ASD incidence and time periods after primary PLIF, (2) repeat ASD incidence and time periods, and (3) ASD incidence and time periods by fusion length, age, and preoperative pathologies. Methods: A total of 1000 patients (average age 67 years, average follow-up 8.3 years) who underwent PLIF for degenerative lumbar disorders were reviewed. ASD was defined as a symptomatic condition in which revision surgery was required. Results: The overall ASD rate was 9.0%, and the average ASD period was 4.7 years after primary surgery. With respect to clinical features of ASD, degenerative spondylolisthesis at the cranial fusion segment was the most frequent. In terms of repeat ASD, second and third ASD incidences were 1.1% and 0.4%, respectively. As for ASD by fusion length, age, and preoperative pathologies, ASD incidence was increased by fusion length, while the time period to ASD was significantly shorter in elderly patients and those with degenerative lumbar scoliosis. Conclusions: In the present study, the overall ASD incidence was 9.0%, and the average ASD period was 4.7 years after primary operation. Second and third ASD incidences were 1.1% and 0.4%, respectively. Fusion length affected the ASD incidence, while aging factor and preoperative pathology affected the ASD time period.

Study design A retrospective study. Objective The purpose of this study was to investigate: (1) patient-based surgical outcomes of posterior lumbar interbody fusion (PLIF); (2) correlations between patient-based surgical outcomes and surgeon-based surgical outcomes; (3) factors associated with patient satisfaction. Summary of background data There have been no reports of patient-based surgical outcomes of PLIF for lumbar spondylolisthesis. Methods Patients who underwent PLIF for L4 degenerative spondylolisthesis between 2006 and 2009 were reviewed (n = 121). Surgical outcomes were assessed 5 years after primary surgery using a questionnaire, a numerical rating scale (NRS) of pain, the 36-Item Short Form Health Survey (SF-36), the Japanese Orthopedic Association score (JOA score), and the recovery rate. The original questionnaire consisted of 5 categories, with scoring out of 100 points for surgery, satisfaction, improvement, recommendation to others, and willingness to undergo repeat surgery. Patient-based outcomes were divided into 3 groups according to the questionnaire responses as positive, intermediate, and negative and were compared with the JOA scores. Results A total of 103 patients responded, for a response rate of 85%. The average patient-evaluated score for surgery was 82 points. The positive response rate in each category was 78% for satisfaction, 88% for improvement, 74% for recommendation, and 71% for repeat. The average pre- and postoperative JOA scores were 11.2 and 23.2, respectively. The average recovery rate was 68.5%. There were significant correlations between patient-based surgical outcomes and the JOA score. Furthermore, there were significant correlations between patient-based surgical outcomes and the NRS and physical component scores of the SF-36. Postoperative permanent motor loss was a major factor related to a negative response. Conclusion The patient-evaluated score for surgery was 82 points. More than 70% of patients gave positive responses in all sections of the questionnaire. There were significant correlations between patient-based and surgeon-based surgical outcomes. Level of evidence 2.

Case A 48-year-old woman underwent anterior cervical discectomy and fusion at C5/6. Extubation was performed immediately after surgery. Tachycardia, limb tremor, and panic attack developed approximately 4 hours after surgery at 16:15. Thirty minutes later, cessation of respiration occurred at 16:50. An experienced anesthesiologist attempted intubation but was unsuccessful because of laryngopharyngeal edema at the C2 level. Finally, an otolaryngologist performed tracheotomy and secured the airway at 17:20 but hypoxic encephalopathy ensued. Conclusion Predicting the airway obstruction caused by laryngopharyngeal edema was very difficult; hence, to prevent critical complications, systematic perioperative management is essential in anterior cervical spine surgery.

Study Design Retrospective clinical study. Objective To investigate the age-related surgical outcomes of laminoplasty. Methods One hundred patients who underwent an en bloc laminoplasty for cervical spondylotic myelopathy from 2004 to 2008 and were followed for at least 1 year were included in this study. The clinical outcomes were assessed with the Japanese Orthopaedic Association (JOA) score. Acquired points (postoperative JOA score minus preoperative JOA score) were also calculated. To investigate the age-related effect for laminoplasty, two analyses were conducted: (1) the correlation between age and clinical outcome; and (2) the clinical outcomes by decade. Patients were divided into four groups according to their age at the time of operation as follows: group 50s, 50 to 59 years old; group 60s, 60 to 69 years; group 70s, 70 to 79 years; and group 80s, 80 to 89 years. The pre- and postoperative JOA scores, acquired points, preoperative comorbidities, and postoperative complications were then compared among the groups. Results Significant correlations were detected between age and JOA scores at the preoperative ( p = 0.03), postoperative maximum ( p Conclusions Although an age-related decline of JOA scores was found over all periods, there were no severe sequelae and no differences in the acquired points that were age-related.

Study Design Case report. Objective To present two cases of neurogenic shock that occurred immediately following posterior lumbar interbody fusion (PLIF) and that appeared to have been caused by the vasovagal reflex after dural injury and incarceration of the cauda equina. Case Report We present two cases of neurogenic shock that occurred immediately following PLIF. One patient had bradycardia, and the other developed cardiac arrest just after closing the surgical incision and opening the drainage tube. Cardiopulmonary resuscitation was performed immediately, and the patients recovered successfully, but they showed severe motor loss after awakening. The results of laboratory data, chest X-ray, electrocardiogram, computed tomography, and echocardiography ruled out pulmonary embolism, hemorrhagic shock, and cardiogenic shock. Although the reasons for the postoperative shock were obscure, reoperation was performed to explore the cause of paralysis. At reoperation, a cerebrospinal fluid collection and the incarceration of multiple cauda equina rootlets through a small dural tear were observed. The incarcerated cauda equina rootlets were reduced, and the dural defect was closed. In both cases, the reoperation was uneventful. From the intraoperative findings at reoperation, it was thought that the pathology was neurogenic shock via the vasovagal reflex. Conclusion Incarceration of multiple cauda equina rootlets following the accidental dural tear by suction drainage caused a sudden decrease of cerebrospinal fluid pressure and traction of the cauda equina, which may have led to the vasovagal reflex.

OBJECTIVE The importance of spinopelvic balance and its implications for clinical outcomes after spinal arthrodesis has been reported in recent studies. However, little is known about the relationship between adjacent-segment disease (ASD) after lumbar arthrodesis and spinopelvic alignment. The purpose of this study was to clarify the relationship between spinopelvic radiographic parameters and symptomatic ASD after L4–5 single-level posterior lumbar interbody fusion (PLIF). METHODS This was a retrospective 1:5 matched case-control study. Twenty patients who had undergone revision surgery for symptomatic ASD after L4–5 PLIF and had standing radiographs of the whole spine before primary and revision surgeries were enrolled from 2005 to 2012. As a control group, 100 age-, sex-, and pathology-matched patients who had undergone L4–5 PLIF during the same period, had no signs of symptomatic ASD for more than 3 years, and had whole-spine radiographs at preoperation and last follow-up were selected. Mean age at the time of primary surgery was 68.9 years in the ASD group and 66.7 years in the control group. Several radiographic spinopelvic parameters were measured as follows: sagittal vertical axis (SVA), thoracic kyphosis (TK), sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), lumbar lordosis (LL), and segmental lordosis at L4–5 (SL) in the sagittal view, and C7–central sacral vertical line (C7-CSVL) in the coronal view. Radiological parameters were compared between the groups. RESULTS No significant change was found between pre- and postoperative radiographic parameters in each group. In terms of preoperative radiographic parameters, the ASD group had significantly lower LL (40.7° vs 47.2°, p < 0.01) and significantly higher PT (27° vs 22.9°, p < 0.05) than the control group. SVA ≥ 50 mm was observed in 10 of 20 patients (50%) in the ASD group and in 21 of 100 patients (21%, p < 0.01) in the control group. PI-LL ≥ 10° was noted in 15 of 20 patients (75%) in the ASD group and in 40 of 100 patients (40%, p < 0.01) in the control group on preoperative radiographs. Postoperatively, the ASD group had significantly lower TK (22.5° vs 30.9°, p < 0.01) and lower LL (39.3° vs 48.1°, p < 0.05) than the control group had. PI-LL ≥ 10° was seen in 15 of 20 patients (75%) in the ASD group and in 43 of 100 patients (43%, p < 0.01) in the control group. CONCLUSIONS Preoperative global sagittal imbalance (SVA > 50 mm and higher PT), pre- and postoperative lower LL, and PI-LL mismatch were significantly associated with ASD. Therefore, even with a single-level PLIF, appropriate SL and LL should be obtained at surgery to improve spinopelvic sagittal imbalance. The results also suggest that the achievement of the appropriate LL and PI-LL prevents ASD after L4–5 PLIF.

One of the most important sequelae affecting long-term results is adjacent-segment degeneration (ASD) after posterior lumbar interbody fusion (PLIF). Although several reports have described the incidence rate, there have been no reports of repeated ASD. The purpose of this report was to describe 1 case of repeated ASD after PLIF. A 62-year-old woman with L-4 degenerative spondylolisthesis underwent PLIF at L4–5. At the second operation, L3–4 PLIF was performed for L-3 degenerative spondylolisthesis 6 years after the primary operation. At the third operation, L2–3 PLIF was performed for L-2 degenerative spondylolisthesis 1.5 years after the primary operation. Vertebral collapse of L-1 was detected 1 year after the third operation, and the collapse had progressed. At the fourth operation, 3 years after the third operation, vertebral column resection of L-1 and replacement of titanium mesh cages with pedicle screw fixation between T-4 and L-5 was performed. Although the patient's symptoms resolved after each operation, the time between surgeries shortened. The sacral slope decreased gradually although each PLIF achieved local lordosis at the fused segment.

OBJECTIVE Tranexamic acid (TXA), a synthetic antifibrinolytic drug, has been reported to reduce blood loss in orthopedic surgery, but there have been few reports of its use in spine surgery. Previous studies included limitations in terms of different TXA dose regimens, different levels and numbers of fused segments, and different surgical techniques. Therefore, the authors decided to strictly limit TXA dose regimens, surgical techniques, and fused segments in this study. There have been no reports of using TXA for prevention of intraoperative and postoperative blood loss in posterior lumbar interbody fusion (PLIF). The purpose of the study was to evaluate the efficacy of high-dose TXA in reducing blood loss and its safety during single-level PLIF. METHODS The study was a nonrandomized, case-controlled trial. Sixty consecutive patients underwent single-level PLIF at a single institution. The first 30 patients did not receive TXA. The next 30 patients received 2000 mg of intravenous TXA 15 minutes before the skin incision was performed and received the same dose again 16 hours after the surgery. Intra- and postoperative blood loss was compared between the groups. RESULTS There were no statistically significant differences in preoperative parameters of age, sex, body mass index, preoperative diagnosis, or operating time. The TXA group experienced significantly less intraoperative blood loss (mean 253 ml) compared with the control group (mean 415 ml; p < 0.01). The TXA group also had significantly less postoperative blood loss over 40 hours (mean 321 ml) compared with the control group (mean 668 ml; p < 0.01). Total blood loss in the TXA group (mean 574 ml) was significantly lower than in the control group (mean 1080 ml; p < 0.01). From 2 hours to 40 hours, postoperative blood loss in the TXA group was consistently significantly lower. There were no perioperative complications, including thromboembolic events. CONCLUSIONS High-dose TXA significantly reduced both intra- and postoperative blood loss without causing any complications during or after single-level PLIF.

The purpose of this retrospective study was to demonstrate the surgical outcomes of anterior spinal fusion (ASF) and posterior subtraction osteotomy (PSO) for osteoporotic vertebral collapse (OVC). Forty patients who underwent surgery for OVC at the thoracolumbar junction with neurological deficits were included in this study. ASF was primarily chosen for patients without vertebral compression fracture at other levels, and PSO was chosen for patients with more severe kyphosis or with multiple vertebral fractures. ASF was performed in 26 patients and PSO was performed in 14 patients. We evaluated the pre- and postoperative clinical status consisting of pain, gait, paralysis, and bladder function analysis. Additionally, pre- and postoperative kyphosis, correction angle, correction loss, and upright balance were investigated radiologically. Improvements in pain level, gait, paralysis, and bladder function were obtained in both groups. Average correction angles in the ASF and PSO groups were 16 and 37, respectively. Average correction losses at the final follow-up in the ASF and PSO groups were 7 and 13, respectively. Newly developed postsurgical vertebral compression fracture adjacent to the level of instrumentation was observed in four patients (15%) in the ASF group and in 11 patients (79%) from the PSO group. ASF provided satisfactory outcomes for patients with thoracolumbar OVC, who have no vertebral compression fracture at other levels. Although PSO has benefits for the correction of kyphosis, several problems persist with this procedure, especially for patients with severe osteoporosis.

Introduction: Posterior lumbar interbody fusion (PLIF) has produced satisfactory clinical outcomes; however, all previous reports have only included evaluations by surgeon-based methods. The purpose of this study was to investigate patient-based surgical outcomes and the factors associated with patient satisfaction for PLIF. Methods: Patients who underwent PLIF for lumbar spondylolisthesis were reviewed (n=443). The average follow-up period was 8 years. Surgical outcomes were assessed using an original questionnaire, a numerical rating scale (NRS), the 36-Item Short Form Health Survey (SF-36), the Japanese Orthopedic Association (JOA) score, and the recovery rate. The original questionnaire consisted of five categories, with patient-evaluated score out of 100 points for surgery, satisfaction, improvement, recommendation to others, and willingness to undergo repeat surgery on a 5-point scale. According to the questionnaire responses, patient-based outcomes were divided into three groups: positive, intermediate, and negative and were compared with the NRS, SF-36, and JOA scores. Furthermore, factors associated with patient satisfaction were examined. Results: A total of 273 patients responded. Response rate was 62%. The average patient-evaluated score for surgery was 82 points. In terms of satisfaction section, positive, intermediate, and negative response rates were 82%, 7%, and 11%, respectively. With respect to other sections, positive, intermediate, and negative response rates were 87%, 7%, and 6% in improvement section; 66%, 23%, and 11% in recommending section; and 72%, 18%, and 10% in repeat section, respectively. The average pre- and postoperative JOA scores were 12 and 24, respectively. Significant correlations were detected between patient-based surgical outcomes and the NRS scores, physical component scores of the SF-36, and the JOA score. Postoperative permanent motor loss and multiple revision surgery were the major factors related to a negative response. Conclusions: High satisfaction rate to PLIF and significant correlation between patient- and surgeon-based surgical outcomes were detected. Postoperative permanent motor loss and multiple revision surgery were the major factors related to a negative response.

RUNX2 is an essential transcription factor for osteoblast differentiation, because osteoblast differentiation is completely blocked in Runx2-deficient mice. However, it remains to be clarified whether RUNX2 is sufficient for osteoblast differentiation during embryogenesis. To address this issue, Runx2 transgenic mice were generated under the control of the Prrx1 promoter, which directs the transgene expression to mesenchymal cells before the onset of bone development. The transgene expression was detected in the cranium, limb buds, and the region from the mandible to anterior chest wall. The skull became small and the limbs were shortened depending on the levels of the transgene expression. Early onset of Runx2 expression in the cranial mesenchyme induced mineralization on E13.0, when no mineralization was observed in wild-type mice, and resulted in craniosynostosis as shown by the closure of sutures and fontanelles on E18.5. Col1a1 and Spp1 expressions were detected in the mineralized regions on E12.5-13.5. The limb bones were hypoplastic and fused, and ectopic bones were formed in the hands and feet. Col2a1 expression was inhibited but Col1a1 expression was induced in the limb buds on E12.5. In the anterior chest wall, ectopic bones were formed through the process of intramembranous ossification, interrupting the formation of cartilaginous anlagen of sternal manubrium. These findings indicate that RUNX2 is sufficient to direct mesenchymal cells to osteoblasts and lead to intramembranous bone formation during embryogenesis; Runx2 inhibits chondrocyte differentiation at an early stage; and that Runx2 expression at appropriate level, times and spaces during embryogenesis is essential for skeletal development.

Runx2 and Sp7 are essential transcription factors for osteoblast differentiation. However, the molecular mechanisms responsible for the proliferation of osteoblast progenitors remain unclear. The early onset of Runx2 expression caused limb defects through the Fgfr1?3 regulation by Runx2. To investigate the physiological role of Runx2 in the regulation of Fgfr1?3, we compared osteoblast progenitors in Sp7?/? and Runx2?/? mice. Osteoblast progenitors accumulated and actively proliferated in calvariae and mandibles of Sp7?/? but not of Runx2?/? mice, and the number of osteoblast progenitors and their proliferation were dependent on the gene dosage of Runx2 in Sp7?/? background. The expression of Fgfr2 and Fgfr3, which were responsible for the proliferation of osteoblast progenitors, was severely reduced in Runx2?/? but not in Sp7?/? calvariae. Runx2 directly regulated Fgfr2 and Fgfr3, increased the proliferation of osteoblast progenitors, and augmented the FGF2-induced proliferation. The proliferation of Sp7?/? osteoblast progenitors was enhanced and strongly augmented by FGF2, and Runx2 knockdown reduced the FGF2-induced proliferation. Fgfr inhibitor AZD4547 abrogated all of the enhanced proliferation. These results indicate that Runx2 is required for the proliferation of osteoblast progenitors and induces proliferation, at least partly, by regulating Fgfr2 and Fgfr3 expression., Scientific Reports, 8(1), art.no.13551; 2018

The Japanese Orthopaedic Association (JOA) scoring system is a physician-based outcome that has been used to evaluate treatment effectiveness after lumbar surgery. However, patient-centered evaluation becomes increasingly important. There is no study that has examined the relationship between the JOA scoring system and patients' self-reported improvement.The purpose of the present study was to validate the JOA scoring system for assessment of patient-reported improvement after lumbar surgery.This is a retrospective review of prospectively collected data.The patient sample included 273 mail-in responders of the 466 consecutive patients who underwent posterior lumbar interbody fusion for spondylolisthesis between 1996 and 2008 in a single hospital.The outcome measures were the JOA scoring system and patients' self-reported improvement.Two hundred seventy three patients were divided into five anchoring groups based on self-reported improvement from "Much better" to "Much worse." Outcomes (ie, recovery rate, amount of change from preoperative condition, and postoperative score) based on the JOA scoring system were compared among groups. Using the patient's self-reported improvement scale as an anchor, the association among each of the outcomes was examined. The cutoff point and the area under the curve (AUC) that differentiated "Improved" from "Neither improved nor worse" was calculated using receiver operating characteristic (ROC) curve analysis.The recovery rate and postoperative score were significantly different in 9 of 10 pairs of anchoring groups. The amount of change was significantly different in six pairs. Spearman correlation coefficient for the 5-point scale anchors of patients' self-reported improvement was 0.20 (p=.001) for the baseline score, 0.31 (p.001) for the amount of change, 0.55 (p.001) for the recovery rate, and 0.56 (p.001) for the postoperative score. According to ROC analysis, the best cutoff points and AUCs were 13 points and 0.69, respectively, for the amount of change, 67% and 0.73, respectively, for recovery rate, and 23 points and 0.72, respectively, for postoperative score.The JOA scoring system is a valid method for assessment of patients' self-reported improvement. Patients' self-reported improvement is more likely to be associated with the final condition, such as postoperative score or recovery rate, rather than the change from the preoperative condition.

Object The management of isthmic spondylolisthesis remains controversial, especially with respect to reduction. There have been no reports regarding appropriate slip reduction. The purpose of this study was to investigate the following issues: 1) surgical outcomes of posterior lumbar interbody fusion (PLIF) with total facetectomy for low-dysplastic isthmic spondylolisthesis, including postoperative complications; 2) effects of slip reduction on surgical outcomes; and 3) appropriate slip reduction. Methods A total of 106 patients who underwent PLIF with total facetectomy for low-dysplastic isthmic spondylolisthesis and who were followed for at least 2 years were reviewed. The average follow-up period was 8 years. Surgical outcomes, including the scores assessed using the Japanese Orthopaedic Association scoring system, the recovery rate, and postoperative complications were investigated. As for radiographic evaluations, pre- and postoperative slip and disc height, instrumentation failure, and fusion status were also examined. Results The pre- and postoperative average Japanese Orthopaedic Association scores were 14 (range 3–25) and 25 (range 11–29) points, respectively. The average recovery rate was 73% (range 0%–100%). The average pre- and postoperative slip was 24% and 10%, respectively. A significant correlation between postoperative slip and clinical outcomes was found; clinical outcomes were better in proportion to slip reduction. Although no statistical difference was detected in clinical outcomes between postoperative slip of less than 10% and from 10% to 20%, patients with postoperative slip of more than 20% showed significantly worse clinical outcomes. Postoperative complications included neurological deficits in 7 patients (transient motor loss in 6 and permanent motor loss in 1), instrumentation failures in 7, adjacent-segment degeneration in 5, and nonunion in 4. Instrumentation failures occurred significantly more often in patients with more slip reduction, although slip reduction did not affect the other postoperative complications. All patients with instrumentation failure showed postoperative slip reduction within 10%. Conclusions The use of PLIF with total facetectomy for low-dysplastic isthmic spondylolisthesis appears to produce satisfactory clinical outcomes, with an average of 73% recovery rate and few postoperative complications. Although clinical outcomes were better in proportion to slip reduction, excessive reduction caused instrumentation failure, and patients with less reduction demonstrated worse clinical outcomes. Appropriate reduction resulted in a postoperative slip ranging from 10% to 20%.

One of the most important sequelae affecting long-term results is adjacent-segment degeneration (ASD) after posterior lumbar interbody fusion (PLIF). Although several reports have described the incidence rate, there have been no reports of repeated ASD. The purpose of this report was to describe 1 case of repeated ASD after PLIF. A 62-year-old woman with L-4 degenerative spondylolisthesis underwent PLIF at L4-5. At the second operation, L3-4 PLIF was performed for L-3 degenerative spondylolisthesis 6 years after the primary operation. At the third operation, L2-3 PLIF was performed for L-2 degenerative spondylolisthesis 1.5 years after the primary operation. Vertebral collapse of L-1 was detected 1 year after the third operation, and the collapse had progressed. At the fourth operation, 3 years after the third operation, vertebral column resection of L-1 and replacement of titanium mesh cages with pedicle screw fixation between T-4 and L-5 was performed. Although the patient's symptoms resolved after each operation, the time between surgeries shortened. The sacral slope decreased gradually although each PLIF achieved local lordosis at the fused segment.

Radiculopathy Due to Fracture of an Inferior Articular Process Anomaly at the 5th Lumbar Vertebra: A Case Report This case report details lumbar radiculopathy due to fracture of an inferior articular process anomaly. The inferior articular process at the 5th lumbar vertebra bifurcated to both ventral and dorsal sides of the superior articular process at the sacrum. The ventral spur was fractured and lay just dorsal to the L5 nerve root. Although this anomaly could not be classified as congenital or acquired, this ventral spur was speculated to be fractured by high-energy trauma, resulting in compression of the nerve root.

Surgical strategy for thoracic disc herniation (TDH) remains controversial. We have performed posterior thoracic interbody fusion (PTIF) by bilateral total facetectomies with pedicle screw fixation. The objectives of this retrospective study are to demonstrate the surgical outcomes of PTIF for TDH.We enrolled 11 patients who underwent PTIF for myelopathy due to TDH and were followed for at least 1 year. The mean age at surgery was 55.2 years and the average period of follow-up was 4.3 years. The levels of operation were T10-T11 in three cases, T12-L1 in three, and T2-T3, T3-T4, T9-T10, T11-T12, and T10-T12 in one case, respectively. The pre- and postoperative clinical status was evaluated according to the modified Frankel grade and the Japanese Orthopaedic Association (JOA) score modified for thoracic myelopathy. Additionally, postoperative complications were assessed. Local kyphosis at the operated segment and status of fusion were evaluated using plain radiographs and computed tomography.Improvement of at least one modified Frankel grade was observed in all but one patient. Average pre- and postoperative JOA scores were 4.9 and 8.8 points, respectively. The average recovery rate was 61%. Bony union was observed in ten cases. One patient's postsurgical outcome resulted in pseudoarthrosis, which required revision surgery due to kyphosis deterioration. Cerebrospinal fluid leakage was observed in one patient postoperatively with neither neurological deficit nor evidence of infection.PTIF has produced satisfactory outcomes for myelopathy due to TDH. Therefore, PTIF is one of the surgical treatments of choice for patients with TDH causing myelopathy.

An 8-year-old girl with systemic-onset juvenile idiopathic arthritis (JIA) required surgical reduction for a dislocated left hip joint following failure of skin traction for 1 week. Unaided walking was achieved by 3 months postoperatively. Incongruence and irregularity of the hip joint remained but may resolve with maturation. Joint laxity caused by synovitis, flexion/adduction contracture with pain, and acetabular dysplasia by growth disturbance apparently caused hip dislocation.

Reduced mechanical stress is a major cause of osteoporosis in the elderly, and the osteocyte network, which comprises a communication system through processes and canaliculi throughout bone, is thought to be a mechanosensor and mechanotransduction system; however, the functions of osteocytes are still controversial and remain to be clarified. Unexpectedly, we found that overexpression of BCL2 in osteoblasts eventually caused osteocyte apoptosis. Osteoblast and osteoclast differentiation were unaffected by BCL2 transgene in vitro. However, the cortical bone mass increased due to enhanced osteoblast function and suppressed osteoclastogenesis at 4 months of age, when the frequency of TUNEL-positive lacunae reached 75%. In the unloaded condition, the trabecular bone mass decreased in both wild-type and BCL2 transgenic mice at 6 weeks of age, while it decreased due to impaired osteoblast function and enhanced osteoclastogenesis in wild-type mice but not in BCL2 transgenic mice at 4 months of age. Rankl and Opg were highly expressed in osteocytes, but Rankl expression in osteoblasts but not in osteocytes was increased at unloading in wild-type mice but not in BCL2 transgenic mice at 4 months of age. Sost was locally induced at unloading in wild-type mice but not in BCL2 transgenic mice, and the dissemination of Sost was severely interrupted in BCL2 transgenic mice, showing the severely impaired osteocyte network. These findings indicate that the osteocyte network is required for the upregulation of Rankl in osteoblasts and Sost in osteocytes in the unloaded condition. These findings suggest that the osteocyte network negatively regulate bone mass by inhibiting osteoblast function and activating osteoclastogenesis, and these functions are augmented in the unloaded condition at least partly through the upregulation of Rankl expression in osteoblasts and that of Sost in osteocytes, although it cannot be excluded that low BCL2 transgene expression in osteoblasts contributed to the enhanced osteoblast function., PLoS ONE, 7(6), e40143; 2012