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Background An epidemiological survey conducted in Japan in fiscal year 2010 revealed a high prevalence of chronic musculoskeletal pain, low patient satisfaction with treatment, a high incidence of protracted treatment lasting a year or more, and reduced quality of life. To improve the current system for treating chronic musculoskeletal pain, it is important to identify risk factors, including patient characteristics, for developing chronic pain. Thus, we sought to determine the incidence of new chronic pain in the Japanese population, as well as the persistence rate, associated factors, and current state of treatment of chronic pain, by repeating a postal survey in a nationwide representative sample group first surveyed in 2010. Methods Among 11,507 participants in the 2010 epidemiological survey, 1,717 reported chronic pain and 6,283 reported no chronic pain. A repeat questionnaire, mailed to subjects in these 2 groups in fiscal year 2011, received replies from 85 % of those who reported pain and 76 % of those without pain in 2010. Results The incidence of new chronic pain was 11.1 %. Risk factors for developing chronic pain included working in a professional, managerial, or clerical/specialist occupation, being female, having a BMI ≥25; currently using alcohol or cigarettes; and having completed an education level of vocational school or higher. Persistent chronic pain was reported by 45.2 % of respondents. Those with severe (VAS score ≥7) and constant lower-back pain lasting more than 5 years had the highest risk of the pain persisting. More than 80 % respondents with persistent chronic pain had a history of treatment, and while about 30 % were still receiving treatment at the time of the survey, the other 50 % had discontinued treatment despite the persistence of pain because of a low degree of satisfaction with treatment. Discussion We identified risk factors related to the development of new chronic pain and the persistence of chronic pain. Countermeasures to prevent chronic pain could be especially important for the high-risk populations for understanding the pathology of chronic pain.

The present study compared simultaneous and two-staged (stages 1 and 2 with 8-month interval on average) bilateral TKAs in terms of postoperative serological status and clinical consequences. The decrease in hemoglobin over 2 weeks postoperatively was similar between groups. C-reactive protein levels and creatine phosphokinase index peaking on day 2 were significantly higher in the simultaneous group than in either staged group (P0.05). Incidence of DVT on day 7 tended to be higher in the simultaneous group, but the difference was not significant. Considering the approximately 8-month interval and 2-month earlier functional recovery with stage 2 TKAs, 6 months were saved with the simultaneous bilateral TKA group. Collectively, simultaneous bilateral TKA is likely to offer a safe and effective procedure in appropriate clinical settings involving anti-bleeding and anti-venous thromboembolism prophylaxis.

Intervertebral disc degeneration is the leading cause of chronic back pain. Recent studies show that raised level of SDC4, a cell-surface heparan sulfate (HS) proteoglycan, plays a role in pathogenesis of disc degeneration. However, in nucleus pulposus (NP) cells of the healthy intervertebral disc, the mechanisms that control expression of SDC4 and its physiological function are unknown. Hypoxia induced SDC4 mRNA and protein expression by ∼2.4- and 4.4-fold (P

Study design A retrospective, observational, and multicenter study. Objective To identify the ideal lower instrumented vertebra (LIV) to prevent distal adding-on after surgical correction of Lenke type 2A curve. Summary of background data LIV level may affect the risk of postsurgical adding-on. The choice of the last touching vertebra (LTV)-the most caudal vertebra of the main thoracic curve that touches the central sacral vertical line when standing-as an appropriate LIV has been validated for Lenke type 1A but not type 2A curve. Methods Radiographs obtained before, immediately after, and 2 years after surgery were evaluated for 116 consecutive patients who underwent posterior thoracic fusion surgery for Lenke type 2A curve. The LIV was proximal to the LTV in 18 patients (PLTV), distal in 43 (DLTV), and at the LTV in 55 (ALTV). Significant independent factors associated with adding-on were analyzed first by univariate analysis, and then by stepwise logistic regression analysis. Results Distal adding-on was present in 16 patients (13.8%) at follow-up: 9 PLTV (50.0%), 3 DLTV (7.0%), and 4 ALTV (7.3%). Adding-on was significantly more common in the PLTV group. One PLTV-group patient required revision surgery to treat adding-on. Univariate analysis identified the following significant factors associated with adding-on: the T2-T5 kyphosis angle and shoulder height before, immediately after, and 2 years after surgery; the lumbar Cobb angle at the 2-year follow-up; the 2-year postoperative lumbar curve correction rate; and the difference between the LIV and the end vertebra, neutral vertebra, and LTV levels. Significant independent risk factors identified by stepwise logistic regression analysis included the clavicle angle at follow-up, the correction rate of the lumbar curve immediately after surgery, and the difference between the LIV and LTV levels. Conclusion A LIV at or distal to the LTV may prevent postoperative adding-on in Lenke type 2A curve. Level of evidence 3.

The aim of this study was to develop a new suture tension sensor for musculoskeletal soft tissue that shows deformation or movements. The suture tension sensor was 10 mm in size, which was small enough to avoid conflicting with the adjacent sensor. Furthermore, the sensor had good linearity up to a tension of 50 N, which is equivalent to the breaking strength of a size 1 absorbable suture defined by the United States Pharmacopeia. The design and mechanism were analyzed using a finite element model prior to developing the actual sensor. Based on the analysis, adequate material was selected, and the output linearity was confirmed and compared with the simulated result. To evaluate practical application, the incision of the skin and capsule were sutured during simulated total knee arthroplasty. When conventional surgery and minimally invasive surgery were performed, suture tensions were compared. In minimally invasive surgery, the distal portion of the knee was dissected, and the proximal portion of the knee was dissected additionally in conventional surgery. In the skin suturing, the maximum tension was 4.4 N, and this tension was independent of the sensor location. In contrast, the sensor suturing the capsule in the distal portion had a tension of 4.4 N in minimally invasive surgery, while the proximal sensor had a tension of 44 N in conventional surgery. The suture tensions increased nonlinearly and were dependent on the knee flexion angle. Furthermore, the tension changes showed hysteresis. This miniature tension sensor may help establish the optimal suturing method with adequate tension to ensure wound healing and early recovery.

Lateral retinacular release is still being performed in patients with recurrent patellar dislocation as an additional procedure with distal realignment or medial patellofemoral ligament (MPFL) reconstruction. However, consensus remains lacking regarding suitable indications for lateral retinacular release. A 20-year-old woman presented with patellar instability in both medial and lateral directions after undergoing lateral retinacular release with MPFL reconstruction. She displayed inherent systemic joint laxity meeting all seven Carter-Wilkinson criteria. Simultaneous MPFL revision and lateral retinaculum reconstruction successfully improved patellar instability in both directions. This case provides an example of iatrogenic medial patellar instability after failed lateral retinacular release.

Scoliosis in children poses serious problems including respiratory problems, trunk imbalance, and depression, as well as detracting from the child’s appearance. Scoliosis can also contribute to back pain later in life. Advanced surgical techniques allow for good correction and maintenance of progressive curves, and growth-sparing treatments are now available for patients with early-onset scoliosis (EOS). Posterior corrective surgeries using pedicle screw (PS) constructs, which allow curves to be corrected in three dimensions, has become the most popular surgical treatment for scoliosis. Several navigation systems and probes have been developed to aid in accurate PS placement. For thoracolumbar and lumbar curves, anterior surgery remains the method of choice. Growth-sparing techniques for treating EOS include growing rods, the Shilla method, anterior stapling, and vertical expandable prosthetic titanium rib, which was originally designed to treat thoracic insufficiency syndrome. However, these advanced surgical techniques do not always offer a perfect solution for pediatric scoliosis, and they are associated with complications such as infections and problems with instrumentation. Surgeons have developed several techniques in efforts to address these complications. We here review historic and recent advances in the surgical treatment of scoliosis in children, the problems associated with various techniques, and the challenges that remain to be overcome.

Secondary degeneration after spinal cord injury (SCI) is caused by increased vascular permeability, infiltration of inflammatory cells, and subsequent focal edema. Therapeutic interventions using neurotrophic factors have focused on the prevention of such reactions to reduce cell death and promote tissue regeneration. Vascular endothelial growth factor (VEGF) is a potent angiogenic and vascular permeability factor. However, the effect of VEGF on SCI remains controversial. VEGF signaling is primarily regulated through two primary receptors, VEGF receptor 1 (VEGF-R1) and VEGF receptor 2 (VEGF-R2). The purpose of this study was to examine the effects of intraperitoneal administration of VEGF-R1- and VEGF-R2-neutralizing antibodies on a mouse model of SCI. VEGF-R1 blockade, but not VEGF-R2 blockade, decreased the permeability and infiltration of inflammatory cells, and VEGF-R2 blockade caused a significant increase in neuronal apoptosis in the acute phase of SCI. VEGF-R2 blockade decreased the residual tissue area and the number of neural fibers in the chronic phase of SCI. VEGF-R2 blockade worsened the functional recovery and prolonged the latency of motor evoked potentials. These data suggest that endogenous VEGF-R2 plays a crucial role in neuronal protection after SCI.

Spinal dumbbell tumors are defined as tumors strangulated by the dura mater or the intervertebral foramen to form an hourglass shape [1]. Most spinal dumbbell tumors are nervous system tumors; 68 % are schwannomas, followed by meningiomas (5 %) [2]. Mesenchymal chondrosarcoma is a malignant tumor with a poor prognosis. Although initially reported by Lightenstein and Bernstein [3] in 1959, a mesenchymal chondrosarcoma originating in the spinal dura mater with a dumbbell shape is a rare phenomenon. Here, we report a case of a dumbbell mesenchymal chondrosarcoma at the lumbar level in a ten-year-old female presenting with sciatic pain and numbness of the right leg.

It has been suggested that noncontact anterior cruciate ligament injury commonly occurs during sports requiring acute deceleration or landing motion and that female athletes are more likely to sustain the injury than male athletes. The purpose of this study was to make task-to-task and male-female comparisons of knee kinematics and kinetics in several athletic activities. Three-dimensional knee kinematics and kinetics were investigated in 20 recreational athletes (10 males, 10 females) while performing hopping, cutting, turning, and sidestep and running (sharp deceleration associated with a change of direction). Knee kinematics and kinetics were compared among the four athletic tasks and between sexes. Subjects exhibited significantly lower peak flexion angle and higher peak extension moment in hopping compared with other activities (P < .05). In the frontal plane, peak abduction angle and peak adduction moment in cutting, turning, and sidestep and running were significantly greater compared with hopping (P < .05). No differences in knee kinematics and kinetics were apparent between male and female subjects. Recreational athletes exhibited different knee kinematics and kinetics in the four athletic motions, particularly in the sagittal and frontal planes. Male and female subjects demonstrated similar knee motions during the four athletic activities.

Purpose To assess the outcomes of our technique involving oblique headless compression screw for arthrodesis of the thumb interphalangeal joint and the distal interphalangeal joints of the other digits. Methods A total of 28 joints (19 thumb interphalangeal and 9 distal interphalangeal) in 23 patients with a mean age of 65 years (range, 58–74 y) were retrospectively analyzed. All operations were performed with the Acutrak2 micro-screw. After the resection of synovium and joint cartilage by a dorsal approach, a 0.88-mm diameter guide wire was inserted at the ulnar side of the proximal phalanx in the thumb and radial side of the middle phalanx in the other digits from proximal to distal to fix the joint obliquely. We verified its position under fluoroscopic control and placed the cannulated screw from proximal to distal over the guide wire. Results Intraoperative rigid fixation was obtained except for 1 case, which required additional K-wire fixation. The overall union rate was 96%. Average time to fusion was 11 weeks (range, 8–30 wk), with 76% achieving union within 3 months. There were 2 complications, 1 nonunion and 1 late infection. Other complications such as dorsal skin necrosis, nail deformity, and paresthesia did not occur. Conclusions Efforts to avoid invasion of the nailbed can be technically demanding. We believe that our proximal to distal technique with oblique placement of the headless compression screw is a straightforward and effective method with a relatively low risk of complication. Type of study/level of evidence Therapeutic IV.

Dumbbell tumors account for 13–18 % [1, 2] of reported spinal cord tumors. Most (71–83 %) dumbbell tumors are neurinomas; dumbbell meningiomas are extremely uncommon, comprising only 2–3.6 %. In approximately two-thirds of the reported cases of dumbbell meningioma, the tumor arose from the thoracic vertebrae. It is very uncommon for a dumbbell meningioma to occur at the level of the cervical vertebrae; our review of the literature revealed only seven such cases. Here, we report a case of dumbbell meningioma arising at the upper cervical level in a 49-year-old woman, who presented with progressive myelopathy.

In women, estrogen deficiency after menopause frequently accelerates osteoclastic bone resorption, leading to osteoporosis, the most common skeletal disorder. However, mechanisms underlying osteoporosis resulting from estrogen deficiency remain largely unknown. Here we show that in bone-resorbing osteoclasts, estrogen-dependent destabilization of hypoxia-inducible factor 1 alpha (HIF1α), which is unstable in the presence of oxygen, plays a pivotal role in promoting bone loss in estrogen-deficient conditions. In vitro, HIF1α was destabilized by estrogen treatment even in hypoxic conditions, and estrogen loss in ovariectomized (Ovx) mice stabilized HIF1α in osteoclasts and promoted their activation and subsequent bone loss in vivo. Osteoclast-specific HIF1α inactivation antagonized bone loss in Ovx mice and osteoclast-specific estrogen receptor alpha deficient mice, both models of estrogen-deficient osteoporosis. Oral administration of a HIF1α inhibitor protected Ovx mice from osteoclast activation and bone loss. Thus, HIF1α represents a promising therapeutic target in osteoporosis.

The prevalence of radiographic cervical ossification of the posterior longitudinal ligament (OPLL) in 1,562 Japanese from a population-based cohort was 1.9 %. The presence of OPLL showed a significant association with the femoral neck bone mineral density (BMD), presence of diffuse idiopathic skeletal hyperostosis (DISH) and plasma pentosidine levels. Only one new case of radiographic OPLL was detected, but OPLL progressed in all affected subjects.The purpose of this study was to clarify the prevalence and progression of radiographic OPLL and the associated factors, using the population-based cohort Research on Osteoarthritis/osteoporosis Against Disability (ROAD).In the ROAD study, 1,690 participants underwent X-ray examination of the entire spine and both knees. Radiographic OPLL, lumbar spondylosis, knee osteoarthritis and DISH were diagnosed by a single, well-experienced orthopaedic surgeon. An interviewer-administered questionnaire and tests for anthropometric measurements were administered, and the BMDs of the lumbar spine and proximal femur were determined. A new OPLL case was considered if heterotopic ossification in the posterior longitudinal ligament was absent at baseline but present during follow-up. Progression was defined as an increase in the maximum length or width of the ossification at follow-up over that at baseline.Radiographic OPLL was detected in 30 (17 men, 13 women) of 1,562 individuals who underwent X-ray examination of the cervical spine (prevalence = 1.9 %). Its prevalence was significantly higher in men than in women (p = 0.007), but no association with age was observed. In a logistic regression analysis, OPLL showed a significant association with the femoral neck BMD, presence of DISH and plasma pentosidine levels. Only one new case of radiographic OPLL was detected, but OPLL progressed in all affected subjects.This population-based study clarified the prevalence of radiographic OPLL in the Japanese population as well as its progression. OPLL showed significant association with plasma pentosidine levels, BMD and DISH.

Objective: Myxofibrosarcoma is clinically characterized by a high frequency of local recurrence after surgery. To improve the clinical outcome of patients with myxofibrosarcoma, it is imperative to control any postsurgical local recurrence. Methods: In this study, we performed a retrospective clinicopathologic analysis of 100 consecutive patients with myxofibrosarcoma to identify factors related to poor prognosis. All of the patients had been diagnosed, and had undergone surgery at the National Cancer Center Hospital between 1999 and 2008. Results: At the initial visit to our hospital, 64 patients had primary myxofibrosarcoma, whereas 36 had undergone primary unplanned resection at other facilities. Of the 36 patients, 11 consulted our hospital before recurrence and 25 did so after recurrence. A histologically positive margin after surgery was evident in 28% of the cases overall. The estimated 5-year recurrencefree survival rate was 74.8%. Univariate analysis showed that primary unplanned resection at another facility (P ¼ 0.0001) and a histologically positive margin (P ¼ 0.0224) were significant predictors of local recurrence. When these two factors were subjected to multivariate analysis, only primary unplanned resection at another facility was significantly correlated with the estimated recurrence-free survival rate (P ¼ 0.0011). Primary unplanned resection was also significantly related to the 5-year disease-free survival rate (P ¼ 0.0401). Conclusions: Our findings indicate that primary unplanned resection at a non-referral hospital is the most important risk factor related to poor prognosis of myxofibrosarcoma. Accurate diagnosis and adequate initial surgery are most important factors for improving the clinical outcomes of myxofibrosarcoma.

Our objective was to facilitate ligament tissue reconstruction by characterizing the mechanism of expression of ligament tissue. To accomplish this, we searched for proteins specific to the tissue and introduced them into mesenchymal stem cells. In the two-dimensional phosphorescent gel electrophoresis, the spots in common with the normal human ligament tissue were selected after removing the spots of the normal bone tissue from those of the ossified tissue in the spinal ligament. Proline/arginine-rich end leucine-rich repeat protein (PRELP) was identified in ligament-specific locations by liquid chromatography-tandem mass spectrometry. Transfection of PRELP into mouse mesenchymal stem cells yielded ligament-like connective tissue comprised of parallel fibers. Thus, expression of the PRELP protein could reconstruct the ligament tissue. Since zinc-related proteins were found with high incidence as a result of an array analysis of PRELP's ProtoArray, it was considered that there is a relationship to the zinc metabolism. Tissue induction was mediated by the tumor necrosis factor (TNF)-α via the zinc pathway. PRELP may be a useful gene in syndesmoplasty, provided zinc is present for tissue reconstruction. Chromosome division becomes active with the addition of zinc, and rapid tissue induction takes place in the presence of zinc and TNF-α. Currently, the reconstruction of a ruptured ligament tissue is difficult, but we expect that the PRELP protein expression may facilitate this process. This study describes the discovery of the gene responsible for the differentiation of stem cells into ligament tissue. This important finding may lead to treatments for gonarthrosis, cruciate ligament, and periodontal ligament ruptures, and ossification of the posterior longitudinal ligament.

A retrospective case series.To evaluate the long-term effectiveness and problems of total en bloc spondylectomy (TES) for treating metastatic thyroid cancer of the spine.Although TES is indicated for low-grade malignant spinal tumors, its efficacy in treating thyroid cancer metastases in the spine is uncertain.This study followed 8 patients who underwent TES for spinal metastasis of thyroid cancer (5 males, 3 females; mean age, 55.3 y; mean follow-up period, 6.4 y), 6 with follicular carcinomas and 2 with papillary carcinomas. In 6 patients without a marked paravertebral tumor extension, TES was performed using a posterior approach. Two patients had prominent anterior or anterolateral tumor extension into the thoracic and retroperitoneal cavities, and a combined anterior and posterior approach was used. We evaluated the patients' clinical symptoms, operative procedures, complications, and prognoses.Before surgery, the patients' neurological status was evaluated by the Frankel classification (grade C, 4 patients; grade D, 1 patient; grade E, 3 patients) and Tokuhashi scores (9, 1 patient; 11, 2 patients; 13 and 14, 1 patient each; 15, 3 patients). One year after surgery, all the patients had improved by at least a Frankel grade, and 4 patients classified as grade C before surgery had become ambulatory. At the final follow-up (average of 6.4 y), 5 patients had a grade E Frankel classification and 1 had grade D, but 2 patients had suffered neurological deterioration, because of tumor recurrence, at the same level as the TES in one patient and at an adjacent level in the other. At follow-up, all patients were alive; 5 showed no evidence of disease. Two patients experienced rod breakage, at 2.8 and at 3.3 years after TES, and 1 patient suffered an endplate fracture 6 months after TES; this patient developed a late infection, 7 years after TES.TES was effective in controlling spinal thyroid cancer metastasis locally and in preserving the ability to walk. However, instrumentation failure and other late complications arose during the patients' long survival times after TES.

We investigated the characteristics of patients who achieved Japanese-style deep flexion (seiza-sitting) after total knee replacement (TKR) and measured three-dimensional positioning and the contact positions of the femoral and tibial components. Seiza-sitting was achieved after surgery by 23 patients (29 knees) of a series of 463 TKRs in 341 patients. Pre-operatively most of these patients were capable of seiza-sitting, had a lower body mass index and a favourable attitude towards the Japanese lifestyle (27 of 29 knees). According to two-/three-dimensional image registration analysis in the seiza-sitting position, flexion, varus and internal rotation angles of the tibial component relative to the femoral component had means of 148° (sd 8.0), 1.9° (sd 3.2) and 13.4° (sd 5.9), respectively. Femoral surface contact positions tended to be close to the posterior edge of the tibial polyethylene insert, particularly in the lateral compartment, but only 8.3% (two of 24) of knees showed femoral subluxation over the posterior edge. The mean contact positions of the femoral cam on the tibial post were located 7.8 mm (sd 1.5) proximal to the lowest point of the polyethylene surface and 5.5 mm (sd 0.9) medial to the centre of the post, indicating that the post-cam contact position translated medially during seiza-sitting, but not proximally. Collectively, the seiza-sitting position seems safe against component dislocation, but the risks of posterior edge loading and breakage of the tibial polyethylene post remain.Cite this article: Bone Joint J 2013;95-B:782–7.

To clarify risk factors for the development of myelopathy in patients with cervical spondylotic cord compression. The authors reviewed articles in which risk factors for the development of myelopathy in patients with cervical spondylotic cord compression were discussed. Ossification of the posterior longitudinal ligament (OPLL) was also reviewed as a disease which causes cervical cord compression to clarify pathomechanism of the development of myelopathy. Cervical motion segment disorders are considered to be multifactorial, and developmental size of the canal and foramina, pathological encroachment, biomechanical effects, and circulatory deficiencies are always present to some degree. Static and dynamic factors should be considered for the development of myelopathy. To clarify the pathomechanism of the development of myelopathy in patients with cervical spondylotic spinal cord compression, the exact natural history of CSM should be understood. Several predictable risk factors for the development of myelopathy have been proposed in CSM or OPLL studies, but they were not definitive. Further prospective population-based study is needed to clarify the mechanism.

Adolescent idiopathic scoliosis (AIS) is the most common pediatric skeletal disease. We previously reported a locus on chromosome 10q24.31 associated with AIS susceptibility in Japanese using a genome-wide association study (GWAS) consisting of 1,033 cases and 1,473 controls. To identify additional AIS-associated loci, we expanded the study by adding X-chromosome SNPs in the GWAS and increasing the size of the replication cohorts. Through a stepwise association study including 1,819 cases and 25,939 controls, we identified a new susceptibility locus on chromosome 6q24.1 in Japanese (P = 2.25 × 10(-10); odds ratio (OR) = 1.28). The most significantly associated SNP, rs6570507, was in GPR126 (encoding G protein-coupled receptor 126). Its association was replicated in Han Chinese and European-ancestry populations (combined P = 1.27 × 10(-14); OR = 1.27). GPR126 was highly expressed in cartilage, and the knockdown of gpr126 in zebrafish caused delayed ossification of the developing spine. Our results should provide insights into the etiology and pathogenesis of AIS.

The epithelial-mesenchymal transition (EMT) contributes to the malignant progression of cancer cells including acquisition of the ability to undergo metastasis. However, whereas EMT-related transcription factors (EMT-TF) are known to play an important role in the malignant progression of epithelial tumors, their role in mesenchymal tumors remains largely unknown. We show that expression of the gene for Twist2 is downregulated in human osteosarcoma and correlates inversely with tumorigenic potential in mouse osteosarcoma. Forced expression of Twist2 in highly tumorigenic murine osteosarcoma cells induced a slight inhibition of cell growth in vitro but markedly suppressed tumor formation in vivo. Conversely, knockdown of Twist2 in osteosarcoma cells with a low tumorigenic potential promoted tumor formation in vivo, suggesting that Twist2 functions as a tumor suppressor in osteosarcoma cells. Furthermore, Twist2 induced expression of fibulin-5, which has been reported as a tumor suppressor. Medium conditioned by mouse osteosarcoma cells overexpressing Twist2 inhibited expression of the MMP9 gene as well as invasion in mouse embryonic fibroblasts, and forced expression of Twist2 in osteosarcoma cells suppressed MMP9 gene expression in tumor tissue. Data from the present study suggest that Twist2 inhibits formation of a microenvironment conducive to tumor growth and thereby attenuates tumorigenesis in osteosarcoma.

We hypothesized that the tibial plafond revealed a novel anatomical reference axis associated with the axial alignment through an image processing technique. The plafond axis (PLA) was defined as the line connecting the midpoints of the medial and lateral plafond margin. In terms of intraclass correlation coefficient, the reproducibility to identify the PLA was not less than that to identify a conventional trans-malleolar axis (TMA). When the proximal medial-lateral axis was applied, the tibial torsion with reference to the PLA and the TMA was 12.0° ± 8.4°, and 23.3° ± 8.6°, respectively. The PLA can be considered a reproducible reference and is expected to be applicable in preoperative planning as well as postoperative evaluation of the implant alignment in total knee arthroplasty.

Object The authors undertook this study to evaluate curve progression, risk factors for curve progression, and outcomes after decompression surgery in patients with degenerative lumbar scoliosis with minimal to moderate curvature. Methods Of 852 patients with lumbar canal stenosis treated by posterior decompression surgery, 50 patients had a lumbar curve greater than 10° at final follow-up. These patients were divided into 2 groups according to curve progression during the follow-up period: the P group (11 patients), with a curve progression of more than 5°, and the NP group (39 patients), with a curve progression of 5° or less. The authors compared preoperative parameters in these 2 groups to elucidate risk factors associated with curve progression and other surgical outcomes. Results The average lumbar curve progression in the total group of 50 patients was 3.4° ± 3.9° (range −2.0° to 22.0°). In the P group the average curve progression was 8.5°, and in the NP group it was 2.0°. Multivariate logistic regression analysis showed no significant association between curve progression and any of the potential risk factors evaluated (including curve magnitude, decompression method, and degenerative intervertebral disc changes). Spur formation, evaluated with the Nathan classification at the concave side of the curve, tended to be greater in the P group, although the difference was not statistically significant. There was no significant difference in revision surgery rate, and none of the patients required arthrodesis due to curve progression. Clinical outcomes, evaluated with the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire and the Scoliosis Research Society 22-question questionnaire, were also similar in the 2 groups. Conclusions Surgical outcomes did not deteriorate in the P group. While curve progression after decompression surgery could not be predicted from the preoperative factors considered, spur formation at the concave side of the curve may be a candidate factor. The results of this study indicate that spinal fixation to halt deformity progression is not always necessary if the patient's pathological condition derives mainly from canal stenosis.

STUDY DESIGN A genetic association study of single nucleotide polymorphisms (SNPs) previously reported to be associated with curve progression of adolescent idiopathic scoliosis (AIS). OBJECTIVE To determine whether the association of 5 SNPs with curve progression reported in Chinese with AIS are replicated in Japanese patients with AIS. SUMMARY OF BACKGROUND DATA AIS is a common spinal deformity and has a strong genetic predisposition. Predicting curve progression is important in clinical practice. The progression of AIS is reported to be associated with a number of genes. Associations with neurotrophin 3, G protein-coupled estrogen receptor, and tissue inhibitor of metalloproteinase 2 have been reported in Han Chinese with AIS; however, there has been no replication study for them. METHODS We recruited 2117 patients with AIS with a Cobb angle of 10° or greater of scoliosis curves. They were grouped into progression and nonprogression groups according to their scoliosis curves. Patients whose scoliotic curves were 40° or greater were included in the progression group, and those whose scoliotic curves were less than 30° and had reached skeletal maturation in the nonprogression group. We evaluated the association of 5 SNPs (rs11063714 in neurotrophin 3, rs3808351, rs10269151, and rs4266553 in G protein-coupled estrogen receptor, and rs8179090 in tissue inhibitor of metalloproteinase 2 with curve progression by comparing risk allele frequencies between the 2 groups and the mean Cobb angle for each genotype. RESULTS We evaluated the progression (N = 880) and nonprogression (N = 492) subjects, and their risk allele frequencies were not significantly different. The mean Cobb angle for each genotype also did not have statistical difference. We found no replication of the association on AIS curve progression in any of the SNPs. CONCLUSION The associations of the 5 SNPs with progression of AIS curve are not definite. Large-scale association studies based on appropriate criteria for progression would be necessary to identify SNPs associated with the curve progression.

Severe cervical kyphosis requiring surgical treatment is rare in patients with neurofibromatosis Type 1 (NF1). When it occurs, however, dystrophic changes in the vertebrae make surgical correction and fusion of the deformity extremely difficult. The authors report on 3 cases of severe cervical kyphosis associated with NF1 that were successfully treated with combined anterior and posterior correction and fusion. All patients underwent halo-gravity traction for approximately 1 month prior to surgery to correct the deformity gradually. Posterior correction and fusion were performed with segmental spinal instrumentation consisting of lateral mass screws, lamina screws, pedicle screws, and polyethylene tape for sublaminar wiring. Anterior spinal fusion was performed using a fibula strut to induce solid bone fusion. All patients used a halo vest for postoperative external fixation. Preoperative CT scans showed dystrophic cervical spine changes, and MR images demonstrated extensive neurofibromas outside the cervical spine in all 3 patients. The preoperative kyphotic angles were as follows: Case 1, 140°; Case 2, 81°; and Case 3, 72°; after halo-gravity traction, the kyphosis angles improved to 50°, 55°, and 51°, respectively; and after surgery, they were 50°, 15°, and 27°, respectively. Solid bone union was observed in all patients at the latest follow-up. All three patients experienced postoperative complications consisting of superficial infection, severe pneumonia, and partial dislocation of the distal fibula graft after removing the halo vest, in one patient each. Although dystrophic cervical vertebral changes in these patients with NF1 complicated the correction of severe cervical kyphosis, the use of preoperative halo-gravity traction, a combination of spinal instrumentations, an anterior strut bone graft, and postoperative halo-vest fixation made it possible to correct the kyphosis, maintain the correction, and achieve solid bone fusion.

Hypothesis The clavicle serves as a strut between the thorax and scapula, and lack of this function could affect shoulder mobility. We hypothesized that clavicular discontinuity changes shoulder kinematics, particularly affecting scapular motion. Materials and methods The study used 14 cadaveric shoulders. Cadavers were stabilized in the sitting position. Manual elevation in the sagittal, scapular, and coronal planes was performed in the intact and clavicular discontinuity models. The thorax-scapula distance and 3-dimensional scapular motion during shoulder elevation were recorded using an electromagnetic tracking device. The differences between the 2 experimental models at each position were analyzed. Results Clavicular discontinuity resulted in a decreased thorax-scapula distance and in reduced external rotation, upward rotation, and posterior tilting of the scapula. The kinematic changes were observed during elevations in all 3 planes but were greatest in the sagittal plane compared with the scapular and coronal planes. Conclusions The findings of this study revealed that discontinuity of the clavicle affects shoulder kinematics. Because of its anatomic shape and position, the clavicle stabilizes the external, upward, and posterior rotation of the scapula during arm movement. This function of the clavicle may assist glenohumeral joint motion and help prevent subacromial impingement.

Despite their nearly universal activation of mammalian target of rapamycin (mTOR) signaling, glioblastomas (GBMs) are strikingly resistant to mTOR-targeted therapy. We analyzed GBM cell lines, patient-derived tumor cell cultures, and clinical samples from patients in phase 1 clinical trials, and find that the promyelocytic leukemia (PML) gene mediates resistance to mTOR-targeted therapies. Direct mTOR inhibitors and EGF receptor (EGFR) inhibitors that block downstream mTOR signaling promote nuclear PML expression in GBMs, and genetic overexpression and knockdown approaches demonstrate that PML prevents mTOR and EGFR inhibitor-dependent cell death. Low doses of the PML inhibitor, arsenic trioxide, abrogate PML expression and reverse mTOR kinase inhibitor resistance in vivo, thus markedly inhibiting tumor growth and promoting tumor cell death in mice. These results identify a unique role for PML in mTOR and EGFR inhibitor resistance and provide a strong rationale for a combination therapeutic strategy to overcome it.

Severe arthritis or derangement of the distal radioulnar joint (DRUJ) leads to instability of the DRUJ, and the subluxation of the ulna causes pain on motion, loss of grip strength, and a restriction of forearm rotation.1 A variety of surgical procedures have been described to treat these.2 In 1912, Darrach described a resection of the ulnar head.3 Although this procedure could successfully restore forearm rotation, serious postoperative complications frequently occurred, such as a further loss of grip strength or pain over the proximal ulnar stump.4,5,6 As an alternative solution, Sauve and Kapandji described a distal radioulnar arthrodesis combined with an intentional pseudarthrosis of the distal ulna.7 Some reports of this technique have shown superior results both clinically and radiographically,8,9,10,11 and hence the Sauve-Kapandji (S-K) procedure has almost replaced Darrach's as the most common resection arthroplasty for the treatment of DRUJ dysfunction. The conventional S-K procedure is contraindicated, however, in patients with extremely poor bone quality, which is often seen in patients with advanced-stage rheumatoid arthritis (RA). Since 1994, we have modified the S-K procedure for the treatment of patients with a severely damaged DRUJ. This modification involves rotating the resected ulnar segment 90° and inserting it into the DRUJ to form a bridge between the eroded ulnar head and the decorticated ulnar notch of the radius to provide ulnar support as well as to maintain the radioulnar width of the wrist (Fig. 1). The extensor carpi ulnaris (ECU) tendon sheath attachment into the ulnar head and shaft is preserved, providing a dynamic stabilizing effect on the proximal stump. Fig. 1 Surgical procedure of the modified Sauve-Kapandji procedure. The resected ulnar segment is rotated 90° and inserted in the curetted distal radio-ulnar joint in existing form to bridge the thinned ulnar head and the sigmoid notch using ... The purpose of this study is to review the radiographic findings following the modified S-K procedure to assess its effectiveness at maintaining the radioulnar width of the wrist, controlling ulnar translocation, and maintaining the pseudarthrosis space.

Background: Several risk factors have been proposed for intervertebral disc degeneration (DD) among adolescent athletes. However, the causes of DD are not well understood, and there have been few prospective studies evaluating DD in adolescents. Purpose: To identify risk factors for DD among adolescent American football (AF) players. Study Design: Cohort study (prevalence); Level of evidence, 2. Methods: This study investigated the relationships between the progression of DD and the following factors: lumbar spine abnormalities on baseline radiographs, body mass index, AF position played (lineman or other), and length of playing career (2 full competitive AF seasons or Results: The mean decrease in signal intensity of the nucleus pulposus was 4.30% ± 11.63% in players who completed 2 AF seasons and 1.41% ± 10.03% in those who did not ( P = .12). Mean visual analog scale scores for LBP at follow-up were significantly higher ( P = .001) in players who had played for 2 full seasons (2.67 ± 2.81) than in those with a shorter career (0.99 ± 1.61). Decreases in signal intensity of the nucleus pulposus after 2 years of playing AF related significantly to playing a lineman position (partial regression coefficient, 3.47%), the presence of Schmorl nodes (partial regression coefficient, 3.58%), and disc herniation (partial regression coefficient, 4.09%). Conclusion: Significant risk factors for DD progression in high school AF players included playing a lineman position, the presence of Schmorl nodes, and disc herniation. Continuing to play AF through 2 years of high school was a risk factor for the onset of LBP.

Biodegradableα-tricalcium phosphate (α-TCP) cement based on the chelate-setting mechanism of inositol phosphate (IP6) was developed. This paper examined the effect of the milling time ofα-TCP powder on the material properties of the cement. In addition, biocompatibility of the result cementin vitrousing osteoblasts andin vivousing rabbit models will be studied as well. Theα-TCP powders were ballmilled using ZrO2beads in pure water for various durations up to 270 minutes, with a single-phaseα-TCP obtained at ballmilling for 120 minutes. The resulting cement was mostly composed ofα-TCP phase, and the compressive strength of the cement was8.5±1.1 MPa, which suggested that the cements set with keeping the crystallite phase of starting cement powder. The cell-culture test indicated that the resulting cements were biocompatible materials.In vivostudies showed that the newly formed bones increased with milling time at a slight distance from the cement specimens and grew mature at 24 weeks, and the surface of the cement was resorbed by tartrate-resistant acid phosphatase-(TRAP-)positive osteoclast-like cells until 24 weeks of implantation. The presentα-TCP cement is promising for application as a novel paste-like artificial bone with biodegradability and osteoconductivity.

Mesenchymal chondrosarcoma (MC) is an extremely rare subtype of chondrosarcoma. A tumor specific fusion gene, HEY1-NCOA2 fusion, was recently identified in this tumor. The finding raises the possibility that the diagnosis of MC can be improved by examining the fusion gene. In the present study, we aimed to evaluate the efficacy of fluorescence in situ hybridization (FISH) in detecting HEY1-NCOA2 fusion for the diagnosis of MC. Specimens from 10 patients diagnosed with MC were used for the study. Dual-color FISH was performed using two different probes that specifically hybridize to HEY1 and NCOA2, respectively. Fusion signals were identified in all but two specimens, in which no signal was detected, presumably because of inadequate sample preparation. In accordance with results of a previous study, FISH analysis was highly sensitive in detecting HEY1-NCOA2 fusion in adequately prepared MC samples. The current study adds further support for the use of HEY1-NCOA2 fusion as a valid diagnostic marker for MC.

Study design A retrospective multi-institutional study. Objective To clarify the distribution of intraoperative blood loss during cervical laminoplasty for ossification of the posterior longitudinal ligament (OPLL), and to identify the radiographical risk factors for the occurrence of major blood loss in patients with OPLL undergoing laminoplasty. Summary of background data The incidence of major intraoperative blood loss during laminoplasty for OPLL is unknown. Methods All patients who underwent cervical laminoplasty for OPLL between April 2005 and March 2008 at 27 institutions across Japan were included in this analysis. We investigated the patients' characteristics and surgical data, and compared the radiographical characteristics of OPLL in patients with and without major blood loss. Results The estimated intraoperative blood loss was reported for 545 patients (429 male and 116 female; mean age, 62.7 yr). The mean intraoperative blood loss was 223 g (median, 130 g; range, minimal to 3350 g). Excluding 1 patient with intraoperative vertebral artery injury, major blood loss greater than 500 g was reported in 45 patients (8.3%). Patients with major blood loss were more likely to have neurological complications (5/45 vs. 12/499) and a longer hospital stay (29.5 d vs. 28.8 d) in comparison with those without major blood loss. The occupying ratio of OPLL was greater in the major blood loss group (48.3% vs. 42.2%; P = 0.02). A multivariate analysis revealed an occupying ratio of 60% or greater to be associated with an increased risk of major intraoperative blood loss (odds ratio, 2.4; 95% confidence interval, 1.1-5.3). Conclusion Laminoplasty for OPLL is associated with a risk of major intraoperative blood loss, which can potentially give rise to devastating postoperative complications. An occupying ratio of 60% or greater is a risk factor for major blood loss during laminoplasty in patients with OPLL.

Bone homeostasis is maintained as a delicate balance between bone-resorption and bone-formation, which are coupled to maintain appropriate bone mass. A critical question is how bone-resorption is terminated to allow bone-formation to occur. Here, we show that TGFβs inhibit osteoclastogenesis and maintain bone-mass through Smad4 activity in osteoclasts. We found that latent-TGFβ1 was activated by osteoclasts to inhibit osteoclastogenesis. Osteoclast-specific Smad4 conditional knockout mice (Smad4-cKO) exhibited significantly reduced bone-mass and elevated osteoclast formation relative to controls. TGFβ1-activation induced expression of Irf8 and Bcl6, both of which encode factors inhibiting osteoclastogenesis, by blocking their negative regulator, Prdm1, in osteoclasts in a Smad4-dependent manner. Reduced bone-mass and accelerated osteoclastogenesis seen in Smad4-cKO were abrogated by Prdm1 deletion. Administration of latent-TGFβ1-Fc to wild-type mice antagonized LPS-induced bone destruction in a model of activated osteoclast-mediated bone destruction. Thus, latent-TGFβ1-Fc could serve as a promising new therapeutic agent in bone diseases marked by excessive resorption.

Whether Propionibacterium acnes (P. acnes) causes surgical-site infections (SSI) after orthopedic surgery is controversial. We previously reported that we frequently find P. acnes in intraoperative specimens, yet none of the patients have clinically apparent infections. Here, we tracked P. acnes for 6 months in a mouse osteomyelitis model. We inoculated P. acnes with an implant into the mouse femur in the implant group; the control group was treated with the bacteria but no implant. We then observed over a 6-month period using optical imaging system. During the first 2 weeks, bacterial signals were detected in the femur in the both groups. The bacterial signal completely disappeared in the control group within 28 days. Interestingly, in the implant group, bacterial signals were still present 6 months after inoculation. Histological and scanning electron-microscope analyses confirmed that P. acnes was absent from the control group 6 months after inoculation, but in the implant group, the bacteria had survived in a biofilm around the implant. PCR analysis also identified P. acnes in the purulent effusion from the infected femurs in the implant group. To our knowledge, this is the first report showing that P. acnes causes SSI only in the presence of an implant.

Although human induced pluripotent stem cell (hiPSC) derivatives are considered promising cellular resources for regenerative medicine, their tumorigenicity potentially limits their clinical application in hiPSC technologies. We previously demonstrated that oncogenic hiPSC-derived neural stem/progenitor cells (hiPSC-NS/PCs) produced tumor-like tissues that were distinct from teratomas. To gain insight into the mechanisms underlying the regulation of tumorigenicity in hiPSC-NS/PCs, we performed an integrated analysis using the Infinium HumanMethylation450 BeadChip array and the HumanHT-12 v4.0 Expression BeadChip array to compare the comprehensive DNA methylation and gene expression profiles of tumorigenic hiPSC-NS/PCs (253G1-NS/PCs) and non-tumorigenic cells (201B7-NS/PCs). Although the DNA methylation profiles of 253G1-hiPSCs and 201B7-hiPSCs were similar regardless of passage number, the methylation status of the global DNA methylation profiles of 253G1-NS/PCs and 201B7-NS/PCs differed; the genomic regions surrounding the transcriptional start site of the CAT and PSMD5 genes were hypermethylated in 253G1-NS/PCs but not in 201B7-NS/PCs. Interestingly, the aberrant DNA methylation profile was more pronounced in 253G1-NS/PCs that had been passaged more than 15 times. In addition, we identified aberrations in DNA methylation at the RBP1 gene locus; the DNA methylation frequency in RBP1 changed as 253G1-NS/PCs were sequentially passaged. These results indicate that different NS/PC clones have different DNA methylomes and that DNA methylation patterns are unstable as cells are passaged. Therefore, DNA methylation profiles should be included in the criteria used to evaluate the tumorigenicity of hiPSC-NS/PCs in the clinical setting.

White matter abnormalities in the CNS have been reported recently in various neurological and psychiatric disorders. Quantitation of non-Gaussianity for water diffusion byq-space diffusional MRI (QSI) renders biological diffusion barriers such as myelin sheaths; however, the time-consuming nature of this method hinders its clinical application. In the current study, we aimed to refine QSI protocols to enable their clinical application and to visualize myelin signals in a clinical setting. For this purpose, animal studies were first performed to optimize the acquisition protocol of a non-Gaussian QSI metric. The heat map of standardized kurtosis values derived from optimal QSI (myelin map) was then created. Histological validation of the myelin map was performed in myelin-deficient mice and in a nonhuman primate by monitoring its variation during demyelination and remyelination after chemical spinal cord injury. The results demonstrated that it was sensitive enough to depict dysmyelination, demyelination, and remyelination in animal models. Finally, its utility in clinical practice was assessed by a pilot clinical study in a selected group of patients with multiple sclerosis (MS). The human myelin map could be obtained within 10 min with a 3 T MR scanner. Use of the myelin map was practical for visualizing white matter and it sensitively detected reappearance of myelin signals after demyelination, possibly reflecting remyelination in MS patients. Our results together suggest that the myelin map, a kurtosis-related heat map obtainable with time-saving QSI, may be a novel and clinically useful means of visualizing myelin in the human CNS.SIGNIFICANCE STATEMENTMyelin abnormalities in the CNS have been gaining increasing attention in various neurological and psychiatric diseases. However, appropriate methods with which to monitor CNS myelin in daily clinical practice have been lacking. In the current study, we introduced a novel MRI modality that produces the “myelin map.” The myelin map accurately depicted myelin status in mice and nonhuman primates and in a pilot clinical study of multiple sclerosis patients, suggesting that it is useful in detecting possibly remyelinated lesions. A myelin map of the human brain could be obtained in

Anterior decompression with fusion (ADF) for patients with cervical ossification of the posterior longitudinal ligament (OPLL) is reportedly associated with a higher incidence of complications than is laminoplasty. However, the frequency of perioperative complications associated with ADF for cervical OPLL has not been fully established. The purpose of this study was to investigate the incidence of perioperative complications, especially neurological complications, following ADF performed to relieve compressive cervical myelopathy due to cervical OPLL.Study participants comprised 150 patients who had undergone ADF for cervical OPLL at 27 institutions between 2005 and 2008. Perioperative--especially neurological--complications occurring within 2 weeks after ADF were analyzed. Preoperative imaging findings, including Cobb angle, between C2 and C7 and occupying ratio of OPLL were investigated. Multivariate analysis with logistic regression was performed to identify independent risk factors for neurological complications.Three patients (2.0 %) showed deterioration of lower-extremity function after ADF. One of the three patients had not regained their preoperative level of function 6 months after surgery. Upper-extremity paresis occurred in 20 patients (13.3 %), five of whom had not returned to preoperative levels 6 months after surgery. Patients with upper-extremity paresis showed significantly higher occupying ratios of OPLL, greater blood loss, longer operation times, fusion of more segments, and higher rates of cerebrospinal fluid leakage than those without paresis. Independent risk factors for upper-extremity paresis were a high occupying ratio of OPLL and large blood loss during surgery.The incidences of deterioration in upper- and lower-extremity functions were 13.3 % and 2.0 %, respectively. Patients with a high occupying ratio of OPLL are at higher risk of developing neurological deterioration.

We have developed novel calcium-phosphate cements (CPCs) based on the chelate-setting mechanism of inositol phosphate (IP6) using hydroxyapatite (HAp), β-tricalcium phosphate (β-TCP) and α-TCP as starting materials. These cements (IP6-HAp, IP6-β-TCP and IP6-α-TCP cements) have different bioresorbability due to the chemical composition of starting materials. In the present study, biocompatibility and bioresorbability of the above three cements and commercially available cement (Biopex®-R) was histologically evaluated in vivo using rabbit model for 4, 8, and 24 weeks, in addition to their dissolution in vitro. The dissolution of these cements increased in the order of IP6-HAp, IP6-β-TCP and IP6-α-TCP cements. The newly-formed bones were directly in contact with both the IP6-HAp and Biopex®-R cement specimens. As for the IP6-β-TCP and IP6-α-TCP cements, newly-formed bones were formed time-dependently slightly apart from the cement specimens. Resorption rate for Biopex®-R, IP6-HAp, IP6-β-TCP, and IP6-α-TCP cements after 24 weeks implantation were of 7.2, 5.0, 13.7, and 16.2%, respectively, compared to original cements. The present chelate-setting cements with different bioresorbability are promising candidates for application as the novel CPCs.

To investigate the frequency of tandem lumbar and cervical intervertebral disc degeneration in asymptomatic subjects.We evaluated magnetic resonance imaging (MRI) results from 94 volunteers (48 men and 46 women; mean age 48 years) for age-related intervertebral disc degeneration in the lumbar and cervical spine.MRI indicated degenerative changes in the lumbar spine in 79 subjects (84 %), with decreased disc signal intensity in 74.5 %, posterior disc protrusion in 78.7 %, anterior compression of the dura in 81.9 %, disc space narrowing in 21.3 %, and spinal canal stenosis in 12.8 %. These findings were more common in older subjects at caudal levels. MRI showed degenerative changes in both the lumbar and cervical spine in 78.7 % of the volunteers.Degenerative findings in both the lumbar and cervical spine, suggesting tandem disc degeneration, was common in asymptomatic subjects. These results provide normative data for evaluating patients with degenerative lumbar and cervical disc diseases.

Macrophage lineage cells such as osteoclasts and foreign body giant cells (FBGCs) form multinuclear cells by cell-cell fusion of mononuclear cells. Recently, we reported that two seven-transmembrane molecules, osteoclast stimulatory transmembrane protein (OC-STAMP) and dendritic cell-specific transmembrane protein (DC-STAMP), were essential for osteoclast and FBGC cell-cell fusion in vivo and in vitro. However, signaling required to regulate FBGC fusion remained largely unknown. Here, we show that signal transducer and activator of transcription 1 (STAT1) deficiency in macrophages enhanced cell-cell fusion and elevated DC-STAMP expression in FBGCs. By contrast, lack of STAT6 increased STAT1 activation, significantly inhibiting cell-cell fusion and decreasing OC-STAMP and DC-STAMP expression in IL-4-induced FBGCs. Furthermore, either STAT1 loss or co-expression of OC-STAMP/DC-STAMP was sufficient to induce cell-cell fusion of FBGCs without IL-4. We conclude that the STAT6-STAT1 axis regulates OC-STAMP and DC-STAMP expression and governs fusogenic mechanisms in FBGCs.

Object This study was conducted to determine whether postoperative changes in the fractional anisotropy (FA) value and diffusion tensor imaging of the cervical spinal cord can predict functional outcome for patients with cervical compressive myelopathy (CCM). Methods Twenty patients with CCM were treated by laminoplasty from 2008 to 2009. Both T2-weighted MRI and diffusion tensor imaging were performed before and after surgery. The FA values were analyzed and fiber tracking was performed. The fiber tract (FT) ratio was calculated according to the following formula: (number of fibers at the compressed level)/(number of fibers at the C-2 level) × 100%. The Japanese Orthopaedic Association scoring system for cervical myelopathy was used to determine pre- and postoperative neurological status of the patients, and the Hirabayashi method was used to calculate the recovery rate. Results There was no significant difference in recovery rates between patients with and those without intramedullary high signal intensity on preoperative T2-weighted images. Substantial differences in FA value among spinal cord, bone, and CSF made it difficult to obtain a precise FA value for the compressed spinal cord. There was a significant correlation between the preoperative FT ratio and the recovery rate (p = 0.0006). A poor outcome (recovery rate < 40%) could be anticipated for CCM patients with preoperative FT ratios below 60%. Conclusions The preoperative FT ratio correlated significantly with the recovery rates in CCM patients. Preoperative diffusion tensor tractography can be a new prognostic predictor for neurological recovery in CCM patients after laminoplasty.

Bone resorption, which is regulated by osteoclasts, is excessively activated in bone destructive diseases such as osteoporosis. Thus, controlling osteoclasts would be an effective strategy to prevent pathological bone loss. Although several transcription factors that regulate osteoclast differentiation and function could serve as molecular targets to inhibit osteoclast formation, those factors have not yet been characterized using a loss of function approach in adults. Here we report such a study showing that inactivation of B-lymphocyte induced maturation protein 1 (Blimp1) in adult mice increases bone mass by suppressing osteoclast formation. Using an ex vivo assay, we show that osteoclast differentiation is significantly inhibited by Blimp1 inactivation at an early stage of osteoclastogenesis. Conditional inactivation of Blimp1 inhibited osteoclast formation and increased bone mass in both male and female adult mice. Bone resorption parameters were significantly reduced by Blimp1 inactivation in vivo. Blimp1 reportedly regulates immune cell differentiation and function, but we detected no immune cell failure following Blimp1 inactivation. These data suggest that Blimp1 is a potential target to promote increased bone mass and prevent osteoclastogenesis.

BACKGROUND: Because an idiopathic spinal extradural arachnoid cyst (SEAC) is rare, its optimal surgical treatment remains controversial. OBJECTIVE: To evaluate the results of surgical treatments for SEACs and to clarify features of the disease associated with poor outcomes. METHODS: Twelve patients with SEACs who underwent surgery at our hospital between 1988 and 2008 were examined retrospectively. The mean follow-up period was 4.7 years. Total resection of the cyst was performed in 7 patients and closure of the dural defect without cyst resection in 5 patients. Surgical outcomes were evaluated with regard to the duration of symptoms, the size of the cyst, and the surgical procedure used. RESULTS: Neurological recovery was observed in all patients, and there was no recurrence. Poor outcomes were observed in patients with a long duration of symptoms (>1 year, P 5 vertebrae, P < .05). The surgical procedure had no significant association with the postoperative neurological recovery. However, there was a significant difference in the degree of the mean postoperative kyphotic angle between the patients treated by total resection of the cyst (9.7 degrees) and those treated by closure of the dural defect without cyst resection through selective laminectomy (2.2 degrees) (P < .01). CONCLUSION: There was no significant difference in postoperative neurological recovery between the 2 surgical procedures. However, closure of the dural defect without cyst resection was less invasive, preventing postoperative kyphotic deformity of the thoracolumbar spine.

Introduction Long-term follow-up studies focusing on the posterior extensor muscles in patients suffering from whiplash injury are scarce. The purpose of this study was to elucidate the changes in the posterior extensor muscles 10 years after whiplash injury. Methods Twenty-three patients who had suffered from whiplash injury in 1994–1996 and had undergone MRI using a 1.5-T superconductive imager participated in this follow-up study (13 males, 10 females, mean age 51.8 years, mean follow-up 11.5 years). In addition, 60 healthy volunteers who had undergone MRI in the same period were included as controls (36 males, 24 females, mean age 47.8 years, mean follow-up 11.1 years). All participants underwent follow-up MRI. The cross-sectional areas of the deep posterior muscles (CSA) including the multifidus, semispinalis cervicis, semispinalis capitis, and splenius capitis were digitally measured at C3-4, C4-5, and C5-6 using NIH image. The long-term changes in the CSA were compared between the two groups. In addition, correlations between the CSA and cervical spine-related symptoms were evaluated. Results The mean total CSA per patient (the sum of the area from C3-4 to C5-6) was 4811.6 ± 878.4 mm 2 in the whiplash patients and 4494.9 ± 1032.7 mm 2 in the controls at the initial investigation ( p = 0.20), and 5173.4 ± 946.1 mm 2 and 4713.0 ± 1065.3 mm 2 at the follow-up ( p = 0.07). The mean change in CSA over time was 361.8 ± 804.9 mm 2 in the whiplash patients and 218.1 ± 520.7 mm 2 in the controls ( p = 0.34). Ten whiplash patients (43.5%) had neck pain and 11 (47.8%) had shoulder stiffness. However, there was no difference in the change in CSA over time between the symptomatic and asymptomatic patients. Conclusions There was no significant difference in the change in CSA between whiplash patients and healthy volunteers after a 10-year follow-up period. In both groups, the cross-sectional area slightly increased at follow-up. In addition, there was no association between the change in CSA and clinical symptoms such as neck and shoulder pain. These results suggest that whiplash injury is not associated with symptomatic atrophy of the posterior cervical muscles over the long term.

Adaptive response to hypoxia in nucleus pulposus cells of the intervertebral disc is regulated by the hypoxia-inducible factors, HIF-1α and HIF-2α. Moreover, oxygen-dependent turnover of HIF-1α in these cells is controlled by the prolyl-4-hydroxylase domain (PHD) family of proteins. Whether HIF homologues control expression of PHDs and whether PHDs control hypoxia-inducible factor (HIF) turnover and/or activity under hypoxia is not known. Here, we show that in nucleus pulposus cells, hypoxia robustly induces PHD3 expression and, to a lesser extent, of PHD2 and PHD1. Reporter analysis shows that the hypoxic induction of the PHD2 promoter is HIF-1α dependent, whereas PHD3 promoter/enhancer activity is dependent on both HIF-1α and HIF-2α. Lentiviral delivery of HIF-1α, ShHIF-1α, and ShHIF-1β confirmed these observations. Noteworthy, HIF-1α maintains basal expression of PHD1 in hypoxia at the posttranscriptional level. Finally, loss of function studies using lentiviral transduction of ShPHDs clearly shows that even at 1% O2, PHD2 selectively degrades HIF-1α. In contrast, in hypoxia, PHD3 enhances HIF-1α transcriptional activity without affecting protein levels. To correlate these observations with disc disease, a condition characterized by tissue vascularization, we analyzed human tissues. Increased PHD1 mRNA expression but decreased PHD2 and PHD3 expression is observed in degenerate tissues. Interestingly, the hypoxic responsiveness of all the PHDs is maintained in isolated nucleus pulposus cells regardless of the disease state. We propose that PHD2 and PHD3 can be used as a biomarker of tissue oxygenation in the disc and that, as such, it may have important clinical implications.

We conducted a prospective follow-up MRI study of originally asymptomatic healthy subjects to clarify the development of Modic changes in the cervical spine over a ten-year period and to identify related factors. Previously, 497 asymptomatic healthy volunteers with no history of cervical trauma or surgery underwent MRI. Of these, 223 underwent a second MRI at a mean follow-up of 11.6 years (10 to 12.7). These 223 subjects comprised 133 men and 100 women with a mean age at second MRI of 50.5 years (23 to 83). Modic changes were classified as not present and types 1 to 3. Changes in Modic types over time and relationships between Modic changes and progression of degeneration of the disc or clinical symptoms were evaluated. A total of 31 subjects (13.9%) showed Modic changes at follow-up: type 1 in nine, type 2 in 18, type 3 in two, and types 1 and 2 in two. Modic changes at follow-up were significantly associated with numbness or pain in the arm, but not with neck pain or shoulder stiffness. Age (≥ 40 years), gender (male), and pre-existing disc degeneration were significantly associated with newly developed Modic changes. In the cervical spine over a ten-year period, type 2 Modic changes developed most frequently. Newly developed Modic changes were significantly associated with age, gender, and pre-existing disc degeneration.

Study design Retrospective case series. Objective To evaluate the treatment strategies for spinal meningioma. Summary of background data Although previous studies have demonstrated favorable surgical outcomes for spinal meningioma, with a low incidence of tumor recurrence, few have examined long-term surgical outcomes. Methods The influence of patient age, surgical margin status (Simpson grade), tumor location, and histological subtype on tumor recurrence were examined retrospectively. In addition, the resected dura mater from Simpson grade I cases was examined for invasive tumor cells and compared with the presence or absence of a dural tail sign on magnetic resonance image. Results Complete resection (Simpson grades I and II) was performed in 62 patients. Among them, the tumor recurrence rate was 9.7%, all in patients who underwent grade II resection for ventral spinal lesions. The mean duration to reoperation in these patients was 12.2 ± 5.2 years. Of the 6 patients who underwent incomplete resection (Simpson grade III/IV), all required reoperation for tumor recurrence or regrowth, 5 years later on average. Patients younger than 50 years at the initial surgery had a significantly higher recurrence rate than those aged 50 years or older. Histologic examination of 43 dura mater specimens from Simpson grade I-resection patients revealed tumor cell invasion between the inner and outer layers in 15 patients. This invasion was noted in 8 (29%) of 28 patients who were negative for the dural tail sign on magnetic resonance image, and in 7 (47%) of 15 patients who showed a positive dural tail sign. The MIB-1 index reached about 10% for dumbbell-type meningiomas invading the vertebral body; these were associated with repeated recurrence and unfavorable prognosis. Conclusion Long-term follow-up after surgery for meningiomas indicated that Simpson grade I resection should be selected whenever practicable when treating younger patients or dumbbell-type meningiomas. Tumors recurred at 12 years, on average, in approximately 30% of patients who underwent grade II resection.

Purpose The objective of this study was to evaluate 2 years post-surgical loss of three-dimensional correction in adolescent idiopathic scoliosis (AIS) patients using multi-planar reconstruction computed tomography (CT).