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Study Design: Case report. Objective: To discuss the development of delayed myelopathy due to the progression of ossification of the posterior longitudinal ligament (OPLL) after cervical laminoplasty. Summary Of Background Data: The progression of OPLL after cervical laminoplasty for the treatment of OPLL is often shown in long-term follow-up; however, few patients with reoperation due to OPLL progression have been reported. Methods: The patient was a 70-year-old male carpenter. At 57-years of age, he underwent open door laminoplasty between C3 and C7 with dome-like laminectomy of C2 for the treatment of myelopathy due to mixed-type OPLL (continuous type at C3-C4 and segmental type at C5). Five years after the initial surgery, the disorder of skilled motor activity in the bilateral hands and ambulatory difficulties recurred as a result of cranial progression of OPLL (between C2 and C4). He underwent laminectomy and posterior fusion between C2 and C5 and returned to work. Four years after resurgery, the same symptoms recurred. Results: CT revealed the progression of OPLL thickness at C5 level and longitudinal progression of OPLL to C6/7. Sagittal view of MRI demonstrated spinal cord compression between C5 and C6/7 because of OPLL at C5 and hypertrophic ligamentum flavum at C5-C6 and C6-C7. Posterior fusion extending up to C7 with laminectomy of C6 and C7 was performed. His symptoms were alleviated and he could walk again. Conclusion: We reported a patient with OPLL who had undergone resurgery twice because of myelopathy due to the progression of ossification. It was important to establish a sufficiently longitudinal and transverse decompression, taking the risk of the unexpected progression of ossification into consideration. [ABSTRACT FROM AUTHOR]

Pedicle screw fixation is frequently used for spinal fusion in elderly patients. The application of pedicle screw fixation for elderly patients with degenerative lumbar disease remains controversial due to problems such as surgical invasion, osteoporosis, and cost performance. Outcomes of spinal fusion using pedicle screw fixation were evaluated in patients older than 70 years with lumbar spinal canal stenosis. Eighty-one patients older than 70 years with degenerative disorders of the lumbar spine were treated with pedicle screw fixation before 1997. They were 70 to 85 years at screw fixation (mean, 74.1 years). The postoperative follow-up period was 3 to 18 years (mean, 8.2 years). The number of fused levels by pedicle screw fixation was 1 to 7 (mean, 2.1), and bone grafting was performed in 19 patients who underwent posterolateral lumbar fusion with posterior lumbar interbody fusion and in 62 (76.5%) who underwent posterolateral lumbar fusion alone. Bone union was radiographically observed in 90.1%. The grade of independence (Independence [Bedridden] Criteria of the Daily Life of the Impaired Elderly) had been rank J (life independence) in all patients 1 year preoperatively, but deteriorated to rank A1 (capable of going out with a helper) in 51.8% of patients and rank B1 (using a wheelchair) in 19.8% immediately preoperatively. The grade of independence was rank J in 85.6% of patients 3 years postoperatively and remained rank J in 40 (87.0%) of the 46 who were alive 10 years postoperatively. Few complications associated with surgical invasion were found, and the grade of independence tended to remain at a high level for 10 years postoperatively. [ABSTRACT FROM AUTHOR]

In general, osteoporosis is evaluated using the bone mineral density (BMD) of the lumbar spine, which can be obtained from dual energy x-ray absorptiometry (DEXA) in lumbar spine radiographs. However, measurements are sometimes difficult in fracture cases, and corrections are necessary among measurement devices or different types of these devices. Furthermore, correlation coefficients vary at different measurement sites. In this study, we attempted to evaluate osteoporosis in tbe pedicle cortex in anteroposterior (AP) views of plain lumbar radiographs.The width of the cortical bone of tbe pedicle (distance between the external and internal margins of the cortical bone) and the cortical bone of the pedicle index in 190 women were determined using AP plain radiographs of the L2 and L3 pedicle, and their relationships with BMD were categorized and investigated by age and BMD (BMD was determined using DEXA).The measurement of the widtb of tbe cortical bone of the pedicle and the cortical bone of the pedicle index for L2 and L3 were found to be suitable for evaluation of the relationship between thickness of tbe cortex of pedicles and osteoporosis. The width of the cortical bone of the pedicle and the cortical bone of the pedicle index for L2 and L3 significantly decreased with age. Correlation coefficients of 0.589 and 0.601 were found between the width of the cortical bone of the pedicle and age and BMD, respectively. Using AP plain lumbar radiographs, the width of the cortical bone of the pedicle for L2 and L3 was determined and a correlation with BMD was obtained. Measurements of the width of the cortical bone of the pedicle may be useful for evaluation of degree of osteoporosis. [ABSTRACT FROM AUTHOR]

Introduction: Mature adipocyte-derived dedifferentiated fat cells (DFATs) represent a subtype of multipotent cells that exhibit comparable phenotypic and functional characteristics to adipose-derived stem cells (ASCs). In this study, we assessed the chondroprotective properties of intra-articularly administrated DFATs in a rat model of osteoarthritis (OA). We also investigated in vitro the expression of anti-inflammatory and chondroprotective genes in DFATs prepared from the infrapatellar fat pad (IFP) and subcutaneous adipose-tissue (SC) of human origin., Methods: In the cell transplantation experiment, rats were assigned to the DFAT and Control group (n = 10 in each group) and underwent anterior cruciate ligament transection (ACLT) accompanied by medial meniscus resection (MMx) to induce OA. One week later, they received intra-articular injections of 1 × 10 6 DFATs (DFAT group) or PBS (control group) four times, with a weekly administration frequency. Macroscopic and microscopic evaluations were conducted five weeks post-surgery. In the in vitro experiments. DFATs derived from the IFP (IFP-DFATs) and SC (SC-DFATs) were prepared from donor-matched tissue samples (n = 3). The gene expression of PTGS2 , TNFAIP6, PRG4, BMP2, and BMP6 under TNF-α or IFN-γ stimulation in these cells was evaluated using RT-PCR. Furthermore, the effect of co-culturing synovial fibroblasts with DFATs on the gene expression of ADAMTS4 and IL-6 were evaluated., Results: Intra-articular injections of DFATs significantly inhibited cartilage degeneration in the rat OA model induced by ACLT and MMx. RT-PCR analysis revealed that both IFP-DFATs and SC-DFATs upregulated the expression of genes involved in immune regulation, anti-inflammation, and cartilage protection such as PTGS2 , TNFAIP6 , and BMP2 , under stimulation by inflammatory cytokines. Co-culture with DFATs suppressed the expression of ADAMTS4 and IL6 in synovial fibroblasts., Conclusions: The intra-articular injection of DFATs resulted in chondroprotective effects in the rat OA model. Both SC-DFATs and IFP-DFATs induced the expression of anti-inflammatory and chondroprotective genes in vitro. These results indicate that DFATs appear to possess therapeutic potential in inhibiting cartilage degradation and could serve as a promising cellular resource for OA treatment., Competing Interests: None., (© 2024 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Background: Mesenchymal stem cells (MSCs) are known to have different differentiation potential depending on the tissue of origin. Dedifferentiated fat cells (DFATs) are MSC-like multipotent cells that can be prepared from mature adipocytes by ceiling culture method. It is still unknown whether DFATs derived from adipocytes in different tissue showed different phenotype and functional properties. In the present study, we prepared bone marrow (BM)-derived DFATs (BM-DFATs), BM-MSCs, subcutaneous (SC) adipose tissue-derived DFATs (SC-DFATs), and adipose tissue-derived stem cells (ASCs) from donor-matched tissue samples. Then, we compared their phenotypes and multilineage differentiation potential in vitro. We also evaluated in vivo bone regeneration ability of these cells using a mouse femoral fracture model., Methods: BM-DFATs, SC-DFATs, BM-MSCs, and ASCs were prepared from tissue samples of knee osteoarthritis patients who received total knee arthroplasty. Cell surface antigens, gene expression profile, and in vitro differentiation capacity of these cells were determined. In vivo bone regenerative ability of these cells was evaluated by micro-computed tomography imaging at 28 days after local injection of the cells with peptide hydrogel (PHG) in the femoral fracture model in severe combined immunodeficiency mice., Results: BM-DFATs were successfully generated at similar efficiency as SC-DFATs. Cell surface antigen and gene expression profiles of BM-DFATs were similar to those of BM-MSCs, whereas these profiles of SC-DFATs were similar to those of ASCs. In vitro differentiation analysis revealed that BM-DFATs and BM-MSCs had higher differentiation tendency toward osteoblasts and lower differentiation tendency toward adipocytes compared to SC-DFATs and ASCs. Transplantation of BM-DFATs and BM-MSCs with PHG enhanced bone mineral density at the injection sites compared to PHG alone in the mouse femoral fracture model., Conclusions: We showed that phenotypic characteristics of BM-DFATs were similar to those of BM-MSCs. BM-DFATs exhibited higher osteogenic differentiation potential and bone regenerative ability compared to SC-DFATs and ASCs. These results suggest that BM-DFATs may be suitable sources of cell-based therapies for patients with nonunion bone fracture., (© 2023. The Author(s).)

Background Context: Although osteoporotic vertebral fractures (OVFs) are the most common type of osteoporotic fracture, few reports have closely investigated the factors contributing to the quality of life (QOL) in the chronic phase after thoracolumbar OVFs using detailed radiographic evaluation., Purpose: This study aimed to identify factors associated with the QOL in the chronic phase after thoracolumbar OVF., Design: Post hoc analysis of a prospective randomized study., Patient Sample: Participants included 195 patients with fresh thoracolumbar OVF managed conservatively with a brace who were available for radiographic analysis 48 weeks after injury., Outcome Measures: The degree of QOL impairment at 48 weeks after thoracolumbar OVF was assessed using the Japanese three-level version of the EuroQol five-dimensional questionnaire (EQ-5D) score., Methods: Univariate and multivariate regression analyses were used to evaluate the relationships between the QOL and radiographic factors., Results: The univariate analysis showed that age, analgesic use, T10/L5 Cobb angle on magnetic resonance imaging (MRI), subsequent vertebral fracture, and nonunion were significantly associated with the EQ-5D score at 48 weeks after thoracolumbar OVF. The multiple regression analysis showed that nonunion, analgesic use, subsequent vertebral fracture, and sacral slope on MRI were independently associated with the EQ-5D score at 48 weeks after thoracolumbar OVF. Receiver operating characteristic analysis for the deterioration of QOL showed that the cutoff value for sacral slope on MRI was 35 degrees., Conclusions: This study demonstrated that nonunion, subsequent vertebral fracture, and lower sacral slope were independently associated with poorer QOL in the chronic phase of thoracolumbar OVF managed conservatively with a brace. Therefore, improving or preventing these factors in patients with thoracolumbar OVF in the chronic phase may improve the QOL of the affected patients., Competing Interests: Declarations of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Although artificial joints using polyethylene have been developed for various joints, the development of Posterior Dynamic Stabilization system of the spine using polyethylene has proceeded at a much slower pace. There are no studies which compare the abrasion resistance of vitamin-E-blended crosslinked polyethylene (VE) and conventional polyethylene (Virgin) in the spinal region. The purpose of this study was to compare the wear resistance of VE and Virgin in a Posterior Dynamic Stabilization System of the spine., Methods: Posterior Dynamic Stabilization System of the spine uses a polyethylene ball as a sliding surface. A fatigue wear test was repeated up to 1 million cycles at a speed of ±5°, 1 Hz while the rod was being pulled at a load of 50 N. Balls were compared using VE and Virgin in 6 samples each. Ti-6AL-4 V (Ti 64) and Co-Cr-Mo (CoCr) rods were used. Abrasion loss and shape change of the polyethylene balls were compared., Results: When Ti 64 was used as the rod, the average wear amount was -0.01 mg (0.02 mg, 0.01 mg, -0.06 mg) for VE, and 0.23 mg (0.18 mg, 0.13 mg, 0.38 mg) for Virgin. When CoCr was used as the rod, the average wear amount was 0.42 mg (0.71 mg, -0.06 mg, 0.61 mg) for VE, and 0.73 mg (0.72 mg, 0.70 mg, 0.76 mg) for Virgin. Most polyethylene samples showed indentations of 0.1 m or less at the contact point with the set screw. In the combination of Virgin and CoCr, a white patch was observed on the inner side of the polyethylene samples, with a maximum depression of 0.1 mm., Conclusions: A fatigue wear test showed VE to be more efficient in abrasion resistance than Virgin in a Posterior Dynamic Stabilization System of the spine in the laboratory., Competing Interests: Declaration of competing interest We received assistance from Teijin Nakashima Medical for the production of screws and materials. We bought prototype screws and materials from Teijin Nakashima Medical. The research was funded by Teijin Nakashima Medical, Neither the funding agency nor any outside organization has participated in study design or have any competing of interest., (Copyright © 2021 The Japanese Orthopaedic Association. All rights reserved.)

Survivin is overexpressed in various cancers and is correlated with treatment resistance and prognosis. MicroRNAs (miRNAs) directly regulate several target genes and are potential therapeutic agents for various cancers. The present study evaluated multiple gene targets of miR‑218, including survivin, in osteosarcoma and compared the anti‑tumor effects of miR‑218 with those of YM155, an anti‑survivin agent. It assessed the expression levels of miR‑218 and survivin in osteosarcoma and osteoblast cell lines, as well as the proliferative, migratory and invasive capacities of cells following treatment with miR‑218 or YM155. The form of cell death was assessed using fluorescence‑activated cell sorting analysis to examine the expression of invasion ability‑related genes. Osteosarcoma cell lines were subcutaneously injected into immunodeficient mice; the mice were then treated with miR‑218 or YM155 to assess the anti‑tumor effects of these agents. The results showed that miR‑218 was downregulated, whereas survivin was overexpressed in the osteosarcoma cell line compared with normal osteoblast cells. The expression of survivin was suppressed upon overexpression of miR‑218 (miR‑218 group) or administration of YM155 (YM155 group), leading to apoptosis and inhibition of osteosarcoma cell proliferation. Invasion and migration abilities were inhibited in the miR‑218 group, but not in the YM155 group. In the animal model, both the miR‑218 and YM155 groups showed a reduced tumor volume and decreased survivin expression. In osteosarcoma, miR‑218 showed a wider range of therapeutic efficacy compared with YM155, suggesting that miR‑218 should be evaluated as a treatment target.

Although osteoporotic vertebral fractures (OVFs) are the most common type of osteoporotic fracture, few reports have investigated the factors contributing to residual low back pain in the chronic phase after OVFs by using radiographic evaluation. We examined the contribution of nonunion, vertebral deformity, and thoracolumbar alignment to the severity of residual low back pain post-OVF. This post hoc analysis of a prospective randomized study included 195 patients with a 48-week follow-up period. We investigated the associations between radiographic variables with the visual analog scale (VAS) scores for low back pain at 48 weeks post-OVF using a multiple linear regression model. Univariate analysis revealed that analgesic use, the local angle on magnetic resonance imaging, anterior vertebral body compression percentage on X-ray, and nonunion showed a significant association with VAS scores for low back pain. Multiple regression analysis produced the following equation: VAS for low back pain at 48 weeks = 15.49 + 0.29 × VAS for low back pain at 0 weeks + (with analgesics: +8.84, without analgesics: -8.84) + (union: -5.72, nonunion: -5.72). Among local alignment, thoracolumbar alignment, and nonunion, nonunion independently contributed to residual low back pain at 48 weeks post-OVF. A treatment strategy that reduces the occurrence of nonunion is desirable.

Introduction: Mature adipocyte-derived dedifferentiated fat cells (DFATs) are mesenchymal stem cell (MSC)-like cells with high proliferative ability and multilineage differentiation potential. In this study, we first examined whether DFATs can be prepared from infrapatellar fat pad (IFP) and then compared phenotypic and functional properties of IFP-derived DFATs (IFP-DFATs) with those of subcutaneous adipose tissue (SC)-derived DFATs (SC-DFATs)., Methods: Mature adipocytes isolated from IFP and SC in osteoarthritis patients (n = 7) were cultured by ceiling culture method to generate DFATs. Obtained IFP-DFATs and SC-DFATs were subjected to flow cytometric and microarray analysis to compare their immunophenotypes and gene expression profiles. Cell proliferation assay and adipogenic, osteogenic, and chondrogenic differentiation assays were performed to evaluate their functional properties., Results: DFATs could be prepared from IFP and SC with similar efficiency. IFP-DFATs and SC-DFATs exhibited similar immunophenotypes (CD73 + , CD90 + , CD105 + , CD31 - , CD45 - , HLA-DR - ) and tri-lineage (adipogenic, osteogenic, and chondrogenic) differentiation potential, consistent with the minimal criteria for defining MSCs. Microarray analysis revealed that the gene expression profiles in IFP-DFATs were very similar to those in SC-DFATs, although there were certain number of genes that showed different levels of expression. The proliferative activity in IFP-DFATs was significantly (p < 0.05) higher than that in the SC-DFATs. IFP-DFATs showed higher chondrogenic differentiation potential than SC-DFATs in regard to production of soluble galactosaminogalactan and gene expression of type II collagen., Conclusions: IFP-DFATs showed higher cellular proliferative potential and higher chondrogenic differentiation capacity than SC-DFATs. IFP-DFAT cells may be an attractive cell source for chondrogenic regeneration., Competing Interests: The authors declare that there is no conflict of interests in this article., (© 2022 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.)

Importance: The optimal management for acute traumatic cervical spinal cord injury (SCI) is unknown., Objective: To determine whether early surgical decompression results in better motor recovery than delayed surgical treatment in patients with acute traumatic incomplete cervical SCI associated with preexisting canal stenosis but without bone injury., Design, Setting, and Participants: This multicenter randomized clinical trial was conducted in 43 tertiary referral centers in Japan from December 2011 through November 2019. Patients aged 20 to 79 years with motor-incomplete cervical SCI with preexisting canal stenosis (American Spinal Injury Association [ASIA] Impairment Scale C; without fracture or dislocation) were included. Data were analyzed from September to November 2020., Interventions: Patients were randomized to undergo surgical treatment within 24 hours after admission or delayed surgical treatment after at least 2 weeks of conservative treatment., Main Outcomes and Measures: The primary end points were improvement in the mean ASIA motor score, total score of the spinal cord independence measure, and the proportion of patients able to walk independently at 1 year after injury., Results: Among 72 randomized patients, 70 patients (mean [SD] age, 65.1 [9.4] years; age range, 41-79 years; 5 [7%] women and 65 [93%] men) were included in the full analysis population (37 patients assigned to early surgical treatment and 33 patients assigned to delayed surgical treatment). Of these, 56 patients (80%) had data available for at least 1 primary outcome at 1 year. There was no significant difference among primary end points for the early surgical treatment group compared with the delayed surgical treatment group (mean [SD] change in ASIA motor score, 53.7 [14.7] vs 48.5 [19.1]; difference, 5.2; 95% CI, -4.2 to 14.5; P = .27; mean [SD] SCIM total score, 77.9 [22.7] vs 71.3 [27.3]; P = .34; able to walk independently, 21 of 30 patients [70.0%] vs 16 of 26 patients [61.5%]; P = .51). A mixed-design analysis of variance revealed a significant difference in the mean change in ASIA motor scores between the groups (F1,49 = 4.80; P = .03). The early surgical treatment group, compared with the delayed surgical treatment group, had greater motor scores than the delayed surgical treatment group at 2 weeks (mean [SD] score, 34.2 [18.8] vs 18.9 [20.9]), 3 months (mean [SD] score, 49.1 [15.1] vs 37.2 [20.9]), and 6 months (mean [SD] score, 51.5 [13.9] vs 41.3 [23.4]) after injury. Adverse events were common in both groups (eg, worsening of paralysis, 6 patients vs 6 patients; death, 3 patients vs 3 patients)., Conclusions and Relevance: These findings suggest that among patients with cervical SCI, early surgical treatment produced similar motor regain at 1 year after injury as delayed surgical treatment but showed accelerated recovery within the first 6 months. These exploratory results suggest that early surgical treatment leads to faster neurological recovery, which requires further validation., Trial Registration: ClinicalTrials.gov Identifier: NCT01485458; umin.ac.jp/ctr Identifier: UMIN000006780.

Purpose: To investigate the incidence and characteristics of subsequent vertebral fracture after osteoporotic vertebral fractures (OVFs) and identify risk factors for subsequent vertebral fractures., Methods: This post-hoc analysis from a prospective randomized multicenter trial included 225 patients with a 48-week follow-up period. Differences between the subsequent and non-subsequent fracture groups were analyzed., Results: Of the 225 patients, 15 (6.7%) had a subsequent fracture during the 48-week follow-up. The annual incidence of subsequent vertebral fracture after fresh OVFs in women aged 65-85 years was 68.8 per 1000 person-years. Most patients (73.3%) experienced subsequent vertebral fractures within 6 months. At 48 weeks, European Quality of Life-5 Dimensions, the Japanese Orthopedic Association Back Pain Evaluation Questionnaire pain-related disorder, walking ability, social life function, and lumbar function scores were significantly lower, while the visual analog scale (VAS) for low back pain was higher in patients with subsequent fracture. Cox proportional hazards analysis showed that a VAS score ≥ 70 at 0 weeks was an independent predictor of subsequent vertebral fracture. After adjustment for history of previous fracture, there was a ~ 67% reduction in the risk of subsequent vertebral fracture at the rigid-brace treatment., Conclusion: Women with a fresh OVF were at higher risk for subsequent vertebral fracture within the next year. Severe low back pain and use of soft braces were associated with higher risk of subsequent vertebral fractures. Therefore, when treating patients after OVFs with these risk factors, more attention may be needed for the occurrence of subsequent vertebral fractures., Level of Evidence: III., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background: Adjacent vertebral fracture (AVF) is a major complication following Balloon Kyphoplasty (BKP). There is no scoring system for predicting AVF using only preoperative elements. The purposes of this study were to develop a scoring system for predicting early AVF after BKP based on preoperative factors and to investigate the appropriate surgical indication for BKP., Methods: Of 220 patients who underwent BKP at a single institution since 2011, 65 patients over the age of 60 who had undergone a standing whole spine X-ray preoperatively were enrolled. Factors affecting the occurrence of early AVF were examined. A scoring system was created consisting of the factors exhibiting significant differences, and the correlation between the total score and the incidence of early AVF was investigated., Results: Twenty of the 65 patients (30.8%) had early AVF. In a univariate analysis, age, previous vertebral fracture, pelvic tilt, and Local kyphosis significantly influenced early AVF. In a multivariate logistic regression analysis, age had an odds ratio of 1.136 (95% CI 1.001-1.289), previous vertebral fractures 4.181 (1.01-17.309), and Local kyphosis 1.103 (1.021-1.191). The scoring system was set as follows: ①Age (<75 years: 0 points(P), 75years≦: 1P), ②The number of previous vertebral fractures (0: 0 P, 1: 1P, 2: 2P, 3 or more: 3P), and ③Local kyphosis (<10°: 0P, 10°≦: 1P). There was a correlation between the total score and the incidence of early AVF (r = 0.812, ∗P = 0.05). The incidence of early AVF was 6.4% (2 cases/31 cases) for a score of ≦1P and 54.5% (18 cases/33 cases) for a score of ≧2P., Conclusions: There was a correlation between the total score and the incidence of early AVF. A score of 1 point or less may represent the appropriate surgical indication for BKP., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Studies on the clinical and radiographic risk factors for the residual low back pain beyond 6 months after osteoporotic vertebral fractures (OVFs) are lacking. Hence, this study aimed to characterize a patient population with residual low back pain 48 weeks after acute OVFs and to identify the risk factors associated with residual low back pain., Methods: This prospective multicenter study included 166 female patients aged 65-85 years with acute one-level OVFs. We defined the residual low back pain as visual analog scale (VAS) for low back pain ≥3.5 at 48 weeks in this study, as VAS score ≥3.5 is used to describe moderate or severe pain. Thus, outcome and risk factor analyses were performed by comparing patients with VAS scores <3.5 and ≥ 3.5. In the radiographic analysis, the anterior vertebral body compression percentage was measured at 0, 12, and 48 weeks. Magnetic resonance imaging (MRI) was performed at enrollment and 48 weeks., Results: Of the 166 patients analyzed, 58 complained of residual low back pain at 48 weeks after OVFs. At 0 weeks, the VAS score was significantly higher, and the JOABPEQ mental health score and anterior vertebral body compression percentage were significantly lower in patients with persistent pain 48 weeks after OVFs. The independent risk factors in the acute phase for persistent pain 48 weeks after OVFs were a high VAS score, MRI T2 fluid-intensity image pattern, and a lower anterior vertebral body compression percentage., Conclusions: Severe low back pain, MRI T2 fluid-intensity image pattern, and severe vertebral body collapse in the acute phase were significant risk factors for residual low back pain 48 weeks after OVFs. Patients with acute OVFs who have these risk factors should be carefully monitored for the possible development of residual chronic low back pain., Competing Interests: Declaration of Competing Interest Hiroaki Nakamura is an associate editor of Journal of Orthopaedic Science. There are no other conflicts of interest., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Purpose: No study has investigated the clinical and radiographic risk factors for the deterioration of quality of life (QOL) beyond 6 months after osteoporotic vertebral fractures (OVF). The purpose of this study was to identify the predictors associated with poor QOL improvement after OVF., Methods: This post hoc analysis included 166 women aged 65-85 years with acute 1-level OVFs. For the patient-reported outcome measures, scores on the European Quality of Life-5 Dimensions (EQ-5D) scale, and visual analogue scale (VAS) for low back pain were used. Lateral radiography at 0, 12, and 48 weeks and magnetic resonance imaging (MRI) at enrollment and at 48 weeks were performed. The associations between baseline variables with change scores for EQ-5D were investigated using a multiple linear regression model., Results: Univariate analysis showed that time since fracture, EQ-5D score, and VAS for low back pain at 0 week showed significant association with increased EQ-5D score from 0 to 48 weeks. According to the multiple regression analysis, the following equation was obtained: increased EQ-5D score from 0 to 48 weeks = 1.305 - 0.978 × EQ-5D at 0 week - 0.021 × VAS for low back pain at 0 week - 0.006 × age + (fluid-intensity T2-weighted MR image patterns: - 0.037, except for fluid-intensity T2-weighted MR image patterns: + 0.037)., Conclusion: In conclusion, older patients with severe low back pain and fluid-intensity T2-weighted MR image patterns were more likely to have lower QOL improvements after OVFs and may therefore need extra support to improve QOL.

Patients with metastatic spinal tumors often experience paralysis caused by spinal cord compression. Several studies have investigated metastatic lesion-related spinal cord compression. This study is the first to examine the relationship between the epidural spinal cord compression (ESCC) scale, which measures circumferential compression, and the functional outcomes of treatment, which were assessed at regular intervals after treatment until death. A total of 191 patients who had grade D or worse paralysis on the American Spinal Injury Association (ASIA) classification scale and a grade 1b or more severe cord compression on the ESCC scale were included in the study. Patients had been treated with surgery combined with radiotherapy (n=146) or radiotherapy alone (n=45). Three spinal surgeons assessed the ESCC grade of for patient, and the grade agreed to by at least 2 surgeons was adopted. After 4 weeks, re-evaluations were conducted by the same examiners. The authors also calculated the mean kappa coefficients for inter- and intra-examiner variability (0.88 and 0.93, respectively). The distribution of the ASIA grade differed significantly among the ESCC scale grades (P=.0102). However, the degree of improvement in paralysis in terms of the ASIA grade (≥1 grade of improvement, no change, or ≥1 grade of aggravation) was not significantly associated with the ESCC grade (P=.2334). The ESCC scale was found to be a useful indicator of circumferential spinal cord compression but was not identified as a significant functional prognostic factor for paralysis. [Orthopedics. 2020;43(6):e567-e573.]., (Copyright 2020, SLACK Incorporated.)

Study Design: Prospective cohort study., Objective: To characterize a patient population with nonunion after acute osteoporotic vertebral fractures (OVFs) and compare the union and nonunion groups to identify risk factors for nonunion., Summary of Background Data: While OVFs are the most common type of osteoporotic fracture, the predictive value of a clinical assessment for nonunion at 48 weeks after OVF has not been extensively studied., Methods: This prospective multicenter cohort study included female patients aged 65 to 85 years with acute one-level osteoporotic compression fractures. In the radiographic analysis, the anterior vertebral body compression percentage was measured at 0, 12, and 48 weeks. Magnetic resonance imaging (MRI) was performed at enrollment and at 48 weeks to confirm the diagnosis and union status. The patient-reported outcome measures included scores on the European Quality of Life-5 Dimensions (EQ-5D), a visual analogue scale for low back pain, and the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) at 0, 12, and 48 weeks., Results: In total, 166 patients completed the 12-month follow-up, 29 of whom had nonunion. Patients with nonunion at 48 weeks after OVF had lower EQ-5D and JOABPEQ walking ability, social life function, mental health, and lumbar function scores than those with union at 48 weeks after injury. The independent risk factors for nonunion after OVF in the acute phase were a diffuse low type pattern on T1-weighted MRI and diffuse low and fluid type patterns on T2-weighted MRI. The anterior vertebral body compression percentage and JOABPEQ social life function scores were independent risk factors at 12 weeks., Conclusion: A diffuse low type pattern on T1-weighted MRI and diffuse low and fluid type patterns on T2-weighted MRI were independent risk factors for nonunion in the acute phase. Patients who have acute OVFs with these risk factors should be carefully monitored for nonunion., Level of Evidence: 2.

Background: The popliteus tendon (PT) or lateral collateral ligament (LCL) stabilizes the postero-lateral aspects of the knees. When surgeons perform total knee arthroplasty (TKA), PT and LCL iatrogenic injuries are a risk because the femoral attachments are relatively close to the femoral bone resection area. The purpose of this study was to evaluate the distance between the PT or LCL footprint and the TKA implant using a 3D template system and to evaluate any significant differences according to the implant model., Methods: Eighteen non-paired formalin fixed cadaveric lower limbs were used (average age: 80.3). Whole length lower limbs were resected from the pelvis. All the surrounding soft tissue except the PT, knee ligaments and meniscus were removed from the limb. Careful dissection of the PT and LCL was performed, and the femoral footprints were detected. Each footprint periphery was marked with a 1.5 mm K-wire. Computed tomography (CT) scanning of the whole lower limb was then performed. The CT data was analyzed with a 3D template system. This simulation models for TKA were the Journey II BCS and the Persona PS. The area of each footprint, and the length between the most distal and posterior point of the lateral femoral condyle and the edge of each footprint were measured. Matching the implant model to the CT image of the femur, the shortest length between each footprint and the bone resection area were calculated., Results: PT and LCL footprint were detected in all knees. The area of the PT and LCL footprints was 38.7 ± 17.7 mm 2 and 58.0 ± 24.6 mm 2 , respectively. The length between the most distal and posterior point of the lateral femoral condyle and the edge of the PT footprint was 10.3 ± 2.4 mm and 14.2 ± 2.8 mm, respectively. The length between most distal and most posterior point of the lateral femoral condyle and the edge of the LCL footprint was 16.3 ± 2.3 mm and 15.5 ± 3.3 mm, respectively. Under TKA simulation, the shortest length between the PT footprint and the femoral bone resection area for the Journey II BCS and the Persona PS was 4.3 ± 2.5 mm and 3.2 ± 2.9 mm, respectively. The shortest length between the LCL footprint and the femoral bone resection area for the Journey II BCS and the Persona PS was 7.2 ± 2.3 mm and 5.6 ± 2.1 mm, respectively. The PT attachment was damaged by the bone resection of the Journey II BCS and the Persona PS TKA in 3 and 9 knees, respectively., Conclusion: The PT and LCL femoral attachments existed close to the femoral bone resection area of the TKA. To prevent postero-lateral instability in TKA, careful attention is needed to avoid damage to the PT and LCL during surgical procedures.

Background: The benefits of surgery for symptomatic spinal metastases have been demonstrated, largely based on series of patients undergoing debulking and instrumentation operations. However, as cancer treatments improve and overall survival lengths increase, the incidence of recurrent spinal cord compression after debulking may increase. The aim of the current paper is to document the postoperative evolution of neurological function, pain, and quality of life following debulking and instrumentation in the Global Spine Tumor Study Group (GSTSG) database., Methods: The GSTSG database is a prospective multicenter data repository of consecutive patients that underwent surgery for a symptomatic spinal metastasis. For the present analysis, patients were selected from the database that underwent decompressive debulking surgery with instrumentation. Preoperative tumor type, Tomita and Tokuhashi scores, EQ-5D, Frankel, Karnofsky, and postoperative complications, survival, EQ-5D, Frankel, Karnofsky, and pain numeric rating scores (NRS) at 3, 6, 12, and 24 months were analyzed., Results: A total of 914 patients underwent decompressive debulking surgery with instrumentation and had documented follow-up until death or until 2 years post surgery. Median preoperative Karnofsky performance index was 70. A total of 656 patients (71.8%) had visceral metastases and 490 (53.6%) had extraspinal bone metastases. Tomita scores were evenly distributed above (49.1%) and below or equal to 5 (50.9%), and Tokuhashi scores almost evenly distributed below or equal to 8 (46.3%) and above 8 (53.7%). Overall, 12-month survival after surgery was 56.3%. The surgery resulted in EQ-5D health status improvement and NRS pain reduction that was maintained throughout follow-up. Frankel scores improved at first follow-up in 25.0% of patients, but by 12 months neurological deterioration was observed in 18.8%., Conclusion: We found that palliative debulking and instrumentation surgeries were performed throughout all Tomita and Tokuhashi categories. These surgeries reduced pain scores and improved quality of life up to 2 years after surgery. After initial improvement, a proportion of patients experienced neurological deterioration by 1 year, but the majority of patients remained stable.

Objective: Caudal epidural blocks often fail due to the difficulty of appropriate needle insertion. This study aimed to evaluate the anatomy of the sacral hiatus using ultrasound imaging., Methods: This was a retrospective study involving 76 patients with spinal disorders. The following factors were analyzed to see if they affected the palpability of the sacral hiatus: sex, body mass index (BMI), and the morphology of the sacral hiatus on ultrasound imaging. The difficulty of needle insertion and the factors that influenced it were investigated in 28 of the 76 patients, who underwent landmark-based caudal epidural block procedures performed by the same doctor., Results: Among the 76 patients, the mean length of the sacral hiatus was 21.3 ± 5.6 mm, the mean distance from the skin to the sacral cornua was 5.2 ± 3.4 mm, and the mean angle of the sacral hiatus was 16.4 ± 5.5 degrees. Sacral base protrusion was present and absent in 35 and 41 cases, respectively. The sacral hiatus exhibited good and poor palpability in 53 and 23 cases, respectively. The mean distance from the skin to the sacral cornua and BMI were found to significantly influence the palpability of the sacral hiatus. Only sacral base protrusion significantly influenced the difficulty of needle insertion., Conclusion: The mean distance from the skin to the sacral cornua and BMI were found to be associated with the palpability of the sacral hiatus, and sacral base protrusion was demonstrated to be associated with the difficulty of needle insertion into the sacral hiatus., (© 2019 World Institute of Pain.)

Purpose: The prognosis of hepatocellular carcinoma (HCC) has recently improved, and so clinicians have greater opportunity to treat HCC-derived spinal metastases. Therefore, predicting life expectancy is important for determining the optimal treatment strategy for such tumors. This study aimed to investigate the prognostic factors for HCC-derived metastatic spine tumors and to develop a scoring system for predicting life expectancy in such cases., Methods: The posttreatment survival time and factors that might influence it were investigated in 62 patients with HCC-derived metastatic spine tumors who were treated at our department (surgery: 27 patients and conservative treatment: 35 patients), and a prognostic scoring system for predicting life expectancy was developed by combining the factors that significantly influenced survival., Results: In the univariate analyses, sex, the patient's general condition, the presence/absence of major internal organ metastasis, the total revised Tokuhashi score, the serum albumin level, Child-Pugh class, spinal surgery, and bone-modifying agent (BMA) treatment were found to influence the posttreatment survival time. These factors were subjected to multivariate analysis, and a novel scoring system for predicting life expectancy based on the patient's general condition, the serum albumin level (or Child-Pugh class), and BMA treatment was developed. In the retrospective analysis, the concordance rate between the patients' life expectancy and actual survival times was 90.3%., Conclusion: The patient's general condition, the serum albumin level (or Child-Pugh class), and BMA treatment influenced the posttreatment survival times of patients with HCC-derived metastatic spine tumors. A prognostic scoring system based on these factors was proposed.

The patient was a 40-year-old female who had been treated at our hospital for left peroneal tendonitis due to an ankle sprain 2 years earlier. She re-injured that ankle while dancing. The pain in the lateral left foot soon improved, but she had difficulty standing with the left foot in equinus. Complete peroneus longus and brevis tendon ruptures were diagnosed. The ipsilateral semitendinosus and gracilis tendons were harvested and used to reconstruct the tendons. Three months after surgery, the patient was able to stand in equinus, and at 5 months after surgery she resumed her original level of sports activities., Competing Interests: No potential conflict of interest relevant to this article was reported.

Background: Therapeutic intervention has recently been actively performed for metastatic spine tumor even though spinal cord paralysis is not clearly observed, but there has been no report in which the degree of spinal cord compression by tumor was taken into consideration for the paralysis-preventing effect of treatment. Thus, we investigated the neurological outcome after treatment of patients with spinal cord compression in a state of impending paralysis., Methods: A retrospective cohort study. The subjects were 88 patients with epidural spinal cord compression (ESCC) scale 1b or severer compression with American Spinal Injury Association (ASIA) E spinal metastasis. The neurological outcome after the therapeutic intervention was investigated at regular intervals until death. The therapeutic intervention was posterior decompression and stabilization in 18 patients, stabilization without posterior decompression in 15, and radiotherapy in 55 patients (3 groups)., Results: The ASIA aggravation group was comprised of 15 patients, and the severity of paralysis was ASIA A in 3, B in 3, C in 6, and D in 3. Paralysis appeared in 16.7% in the posterior decompression and stabilization group, 13.3% in the posterior stabilization without decompression group, and 18.8% in the radiotherapy group. In the transverse view, the incidence was high in cases with advancement to the intervertebral foramen and circumferential-type advancement, and paralysis developed in more than 20% of ESCC 1c or severer cases. Factors influencing neurological aggravation were investigated, but there was no significant factor., Conclusion: In ESCC 1b or severer cases with ASIA E spinal metastasis, paralysis aggravated after therapeutic intervention in 16.7% in the posterior decompression and stabilization group, 13.3% in the stabilization without decompression group, and 16.7% in the radiotherapy group. There was no significant factor influencing the development of paralysis.

Although low-back pain is considered to be associated with cigarette smoking, the influence of cigarette smoking on the intervertebral discs (IVD) has not been confirmed. We established a rat model of passive cigarette smoking-induced IVD degeneration, and investigated the cytohistological changes in the IVD and the accompanying changes in gene expression. IVD from rats exposed to 8 weeks of passive cigarette smoking were stained with Elastica van Gieson, and exhibited marked destruction of the supportive structure of the reticular matrix in the nucleus pulposus (NP). Positive signals on safranin O, alcian blue, type II collagen and aggrecan staining were decreased in the destroyed structure. Safranin O and type II collagen signals were also decreased in the cartilage end-plate (CEP) after 4- and 8-weeks of cigarette smoking. In the CEP, the potential for apoptosis was increased significantly, as demonstrated by staining for single-strand DNA. However, there were no signs of apoptosis in the NP or annulus fibrosus cells. Based on these findings, we hypothesized that passive cigarette smoking-induced stress stimuli first affect the CEP through blood flow due to the histological proximity, thereby stimulating chondrocyte apoptosis and reduction of the extracellular matrix (ECM). This leads to reduction of the ECM in the NP, destroying the NP matrix, which can then progress to IVD degeneration., Competing Interests: This work was funded in part by Ono Pharmaceutical Co., Ltd., Stryker Japan K. K. and Nakashima Medical Co., Ltd. received by YT. There are no patents, products in development or marketed products associated with this research to declare. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Background: Percutaneous pedicle screw (PPS) fixation has been introduced into palliative surgery for metastatic spine tumors; however, the therapeutic effects of PPS on the outcomes of multidisciplinary treatment for such tumors are unclear. Therefore, the therapeutic impact of PPS was investigated among patients with metastatic spine tumors and with revised Tokuhashi scores of ≤8., Materials and Methods: A total of 47 patients who underwent conventional palliative surgery (posterior decompression and stabilization, 33; posterior stabilization alone, 14) before the introduction of PPS and 38 patients who underwent PPS (posterior decompression and stabilization, 19; posterior stabilization alone, 19) were included. Surgical stress (operative time, blood loss, complications, etc.) and treatment outcomes (postoperative survival time, visual analog scale scores, Frankel classification, and the Barthel index at the final followup) were compared between the conventional and PPS groups., Results: The age of the indicated patients significantly increased after the introduction of PPS ( P < 0.05). Regarding posterior decompression and stabilization, there were no significant intergroup differences in surgical stress or treatment outcomes. As for posterior stabilization alone, there were significant preoperative differences in various parameters between the conventional and PPS groups ( P < 0.01) and also significant postoperative intergroup differences between surgical stress and treatment outcomes ( P < 0.01)., Conclusions: For patients with early-stage metastatic spine tumors, the use of PPS-based posterior stabilization combined with multidisciplinary adjuvant therapy has changed the age range of the patients indicated for surgery and caused significant improvements in surgical stress, postoperative survival time, and Barthel index., Competing Interests: There are no conflicts of interest.

Background: There have been only a few reports of subsequent postoperative vertebral fracture following posterior spinal instrumentation fusion, especially in elderly female patients. This study attempted to evaluate the long-term prevalence of subsequent postoperative vertebral fracture in female patients aged 70 years and older who underwent spine decompression and fusion surgery with pedicle screw fixation., Methods: We retrospectively reviewed prospectively collected data from 125 patients who met our inclusion and exclusion criteria. Patients were divided into 2 groups according to age: patients aged 70 years and older (Group A) and patients aged under 70 years of age (Group B). We evaluated incidence of subsequent postoperative vertebral fractures, type and timing of vertebral fractures, preoperative bone mineral density (BMD), preoperative diagnosis, surgical procedure, number of levels fused, extension of fusion to the lumbosacral junction, and presence of a transverse fixator., Results: Baseline characteristics excluding patients' age were not statistically different between the two groups. Preoperative BMD of Group A was an average 81.7% of the young adult mean (YAM) value and that of Group B was an average 85.1% YAM value. Subsequent postoperative vertebral fractures occurred in 22 (41.5%) of 53 in Group A. On the other hand, fracture occurred in 17 (23.6%) of 72 in Group B. There were significant differences between the groups (p = 0.02). The odds ratio for subsequent vertebral fracture was 2.4 (95% confidence interval: 1.1-5.2) in favor of Group A. Survival analysis showed that the rate of subsequent vertebral fracture was significantly higher in Group A (log-rank test, P = 0.007)., Conclusions: The incidence of subsequent vertebral fracture in patients aged 70 years and older was significantly higher than in patients aged under 70 years of age. In the case of pedicle screw fixation in elderly female patients, it is necessary to note the high risk of subsequent vertebral fracture despite short or non-rigid fusion. Vertebral fracture after posterior fusion surgery even for degenerative lumbar pathology could occur in more than one-third of female patients aged 70 years and older.

Backgrounds: "Anatomical" anterior cruciate ligament (ACL) reconstruction is defined as the functional restoration of the ACL to its native dimensions. It is essential to obtain more accurate predictors of ACL size before surgery. The purpose of this study was to investigate the correlation between the native femoral ACL footprint size and the morphology of the distal femur using three-dimensional CT (3D-CT)., Methods: Thirty non-paired Japanese human cadaver knees were used. All soft tissues around the knee were resected except the ACL. For the evaluation of femoral condyle morphology, trans-epicondylar length (TEL), notch outlet length, axial notch area, and notch width index were measured using 3D-CT. The ACL was cut in the middle, and the femoral bone was cut at the most proximal point of the femoral notch. The ACL was carefully dissected, and the boundaries of the ACL insertion site were outlined on the femoral side. An accurate lateral view of the femoral condyle was photographed with a digital camera. The size of the femoral ACL footprint, length of Blumensaat's line, and the height and area of the lateral wall of the femoral intercondylar notch were measured with ImageJ software., Results: Notch height, lateral notch area, and TEL were significantly correlated with the femoral ACL footprint area. Both axial notch area and notch outlet length were significantly correlated with the femoral mid-substance insertion area., Conclusion: Morphological evaluation using 3D-CT preoperatively may be useful in predicting the femoral ACL footprint size.

While bracing is the standard conservative treatment for acute osteoporotic compression fracture, the efficacy of different brace treatments has not been extensively studied. We aimed to clarify and compare the preventive effect of the different brace treatments on the deformity of the vertebral body and other clinical results in this patient cohort. This multicenter nationwide prospective randomized study included female patients aged 65⁻85 years with acute one-level osteoporotic compression fractures. We assigned patients within four weeks of injury to either a rigid-brace treatment or a soft-brace treatment. The main outcome measure was the anterior vertebral body compression percentage at 48 weeks. Secondary outcome measures included scores on the European Quality of Life-5 Dimensions (EQ-5D), visual analog scale (VAS) for lower back pain, and the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ). A total of 141 patients were assigned to the rigid-brace group, whereas 143 patients were assigned to the soft-brace group. There were no statistically significant differences in the primary outcome and secondary outcome measures between groups. In conclusion, among patients with fresh vertebral compression fractures, the 12-week rigid-brace treatment did not result in a statistically greater prevention of spinal deformity, better quality of life, or lesser back pain than soft-brace., Competing Interests: The authors declare no conflict of interest.

Spontaneous spinal epidural hematoma (SSEH) very rarely develops in infants younger than 1 year old. To our knowledge, no previous case of delayed-onset paralysis induced by SSEH communicated with hematoma in the paraspinal muscle has been reported in the literature. The authors present the case of a 6-month-old girl with a tumor mass on her back who developed a paresis of her bilateral lower limbs. On spinal magnetic resonance imaging, the epidural mass appeared to be a dumbbell type and communicated with the mass in the paraspinal muscle through T12/L1 intervertebral foramen at the right side. After excision of the mass in the paraspinal muscle, hemi-laminectomy of T10-L3 was performed. No solid lesion was also present in the spinal canal and it was found to be an epidural hematoma. No malignancy was observed on pathological examination, and vascular and nerve system tumors were negative. When a tumor mass suddenly develops on the back of an infant and motor impairment of the lower limbs develops as the mass gradually enlarges, differential diagnosis should be performed taking SSEH into consideration.

Aim: Surgery for spinal metastases can improve symptoms, but sometimes complications can negate the benefits. Operations may have different indications, complexities and risks, and the choice for an individual is a tailor-made personalised decision. Previous prognostic scoring systems are becoming out of date and inaccurate. We designed a risk calculator to estimate survival after surgery, to inform clinicians and patients when making management decisions., Methods: A prospective cohort study was performed, including 1430 patients with spinal metastases who underwent surgery. Of them, 1264 patients from 20 centres were used for model development using a Cox frailty model. Calibration slope, D-statistic and C-index were used for model validation based on 166 patients. Follow-up was to death or minimum of 2 years after surgery. Pre-operative indices (examination findings, pain, Karnofsky physical functioning score, and radiology) were assessed., Results: An algorithm to predict survival was constructed including the tumour type, ambulatory status, analgesic use, American Society of Anesthesiologists score, number of spinal metastases, previous radiotherapy or chemotherapy, presence of visceral metastases, cervical or thoracic spine involvement, as predictors. An Internet-based risk calculator was developed based on this algorithm, with similar or improved accuracy compared to other validated prognostic scoring systems (C-index, 0.68; 95% confidence interval, 0.63--0.73, and calibration slope, 1.00; 95% confidence interval, 0.68--1.32)., Conclusion: A large, prospective, surgical series of patients with symptomatic spinal metastases was used to create a validated risk calculator that can help clinicians to inform patients about the most appropriate treatment plan. The calculator is available at www.spinemet.com., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background/aim: miRNA-1(miR-1) is down-regulated in various cancer cells including osteosarcoma cells. This study was conducted to analyze the function of miR-1 in osteosarcoma cells., Materials and Methods: miR-1 expression in osteosarcoma cells was evaluated by qRT-PCR. Cell proliferation was evaluated after transfecting miR-1 by WST8 assay and FACS analysis, both in vitro and in vivo., Results: Overexpression of miR-1 suppressed cell proliferation and induced cell-cycle arrest in the G 0 -G 1 phase by increasing p21 levels via a p53-independent pathway. Overexpression of miR-1 down-regulated PAX3, a potential p21-regulating gene. Moreover, knockdown of PAX3 suppressed cell proliferation by increasing p21 levels, and induced arrest at the G 0 /G 1 phase. Administration of miR-1 showed an in vivo antitumor effect., Conclusion: Overexpression of miR-1 suppressed cell proliferation and induced arrest in the G 0 /G 1 phase by increasing p21 levels via a p53-independent pathway through PAX3 suppression. These results indicate that miR-1 could be a therapeutic target for osteosarcoma., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)