Decrease in pelvic incidence after adult spinal deformity surgery is a predictive factor for progression of hip joint osteoarthritis.

BACKGROUND: This study aimed to evaluate the association between spinopelvic alignment parameters and hip osteoarthritis progression after spinal alignment correction surgery for adult spinal deformity, focusing on the preoperative to postoperative change in spinopelvic alignment. METHODS: This retrospective study enrolled 100 adult spinal deformity patients (196 hip joints) who underwent spinal fusion surgery, after excluding four joints with previous total hip arthroplasty. Acetabular roof obliquity (ARO), center edge angle (CE) and Kellgren and Lawrence (KL) grade were measured in the hip joint. Spinopelvic alignment parameters were measured preoperatively and 1-month postoperatively and the changes (Δ) during this period were calculated. Patients were followed-up for ≥ 5 years and factors associated with KL grade progression at 5-years postoperatively were determined by logistic regression analysis. RESULTS: In the analysis with all cases, KL grade progressed in 23 joints. Logistic regression analysis revealed age (OR: 1.098, 95% CI: 1.007-1.198, p = 0.019), ARO (OR: 1.176, 95% CI: 1.01-1.37, p = 0.026), and Δ PI (OR: 0.791, 95% CI: 0.688-0.997, p < 0.001) as parameters significantly associated with KL grade progression. On the other hand, in the analysis limited to 185 cases with 1-month postoperative KL grade of 0, KL grade progressed in 13 joints. Logistic regression analysis revealed PI-LL (OR: 1.058, 95% CI: 1.001-1.117, p = 0.04), ΔPI (OR: 0.785, 95% CI: 0.649-0.951, p < 0.001), and ΔCobb (OR: 1.127, 95% CI: 1.012-1.253, p = 0.009) as parameters significantly associated with progression. CONCLUSIONS: Both the overall and limited analyzes of this study identified preoperative to postoperative change in PI as parameters affecting the hip osteoarthritis progression after spinal fusion surgery. Decrease in PI might represent preexisting sacroiliac joint laxity. Patients with this risk factor should be carefully followed for possible hip osteoarthritis progression.

Histology and chronological magnetic resonance images of congenital spinal deformity: An experimental study in mice model.

BACKGROUND: The natural history of the congenital spinal deformity and its clinical magnitude vary widely in human species. However, we previously reported that the spinal deformities of congenital scoliosis mice did not progress throughout our observational period according to soft X-ray and MRI data. In this study, congenital vertebral and intervertebral malformations in mice were assessed via magnetic resonance (MR) and histological images. METHODS: Congenital spinal anomalies were chronologically assessed via soft X-ray and 7 T MR imaging. MR images were compared to the histological images to validate the findings around the malformations. RESULTS: Soft X-ray images showed the gross alignment of the spine and the contour of the malformed vertebrae, with the growth plate and cortical bone visible as higher density lines, but could not be used to distinguish the existence of intervertebral structures. In contrast, MR images could be used to distinguish each structure, including the cortical bone, growth plate, cartilaginous end plate, and nucleus pulposus, by combining the signal changes on T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI). The intervertebral structure adjacent to the malformed vertebrae also exhibited various abnormalities, such as growth plate and cartilaginous end plate irregularities, nucleus pulposus defects, and bone marrow formation. In the chronological observation, the thickness and shape of the malformed structures on T1WI did not change. CONCLUSIONS: Spinal malformations in mice were chronologically observed via 7 T MRI and histology. MR images could be used to distinguish the histological structures of normal and malformed mouse spines. Malformed vertebrae were accompanied by adjacent intervertebral structures that corresponded to the fully segmented structures observed in human congenital scoliosis, but the intervertebral conditions varied. This study suggested the importance of MRI and histological examinations of human congenital scoliosis patients with patterns other than nonsegmenting patterns, which may be used to predict the prognosis of patients with spinal deformities associated with malformed vertebrae.

Deep learning-based prediction model for postoperative complications of cervical posterior longitudinal ligament ossification.

PURPOSE: Postoperative complication prediction helps surgeons to inform and manage patient expectations. Deep learning, a model that finds patterns in large samples of data, outperform traditional statistical methods in making predictions. This study aimed to create a deep learning-based model (DLM) to predict postoperative complications in patients with cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: This prospective multicenter study was conducted by the 28 institutions, and 478 patients were included in the analysis. Deep learning was used to create two predictive models of the overall postoperative complications and neurological complications, one of the major complications. These models were constructed by learning the patient's preoperative background, clinical symptoms, surgical procedures, and imaging findings. These logistic regression models were also created, and these accuracies were compared with those of the DLM. RESULTS: Overall complications were observed in 127 cases (26.6%). The accuracy of the DLM was 74.6 ± 3.7% for predicting the overall occurrence of complications, which was comparable to that of the logistic regression (74.1%). Neurological complications were observed in 48 cases (10.0%), and the accuracy of the DLM was 91.7 ± 3.5%, which was higher than that of the logistic regression (90.1%). CONCLUSION: A new algorithm using deep learning was able to predict complications after cervical OPLL surgery. This model was well calibrated, with prediction accuracy comparable to that of regression models. The accuracy remained high even for predicting only neurological complications, for which the case number is limited compared to conventional statistical methods.

Anterior fusion surgery with overcorrection in the treatment of adolescent idiopathic scoliosis with Lenke 1 AR curve type: how to achieve overcorrection and its effect on postoperative spinal alignment.

BACKGROUND: The efficacy of anterior fusion with overcorrection in the instrumented vertebra for Lenke 1 AR type curves has been reported, but how to achieve overcorrection and how overcorrection affects spinal alignment are unclear. The purpose of this study was to identify the factors that cause overcorrection, and to investigate how overcorrection affects postoperative spinal alignment in the surgical treatment of Lenke 1 AR type curves. METHODS: Patients who had anterior surgery for a Lenke type 1 or 2 and lumbar modifier AR (L4 vertebral tilt to the right) type scoliosis and minimum 2-year follow-up were included. The radiographic data were measured at preoperative, postoperative 1 month, and final follow-up. The UIV-LIV Cobb angle was determined as the Cobb angle between the upper instrumented vertebra (UIV) and the lower instrumented vertebra (LIV), and a negative number for this angle was considered overcorrection. The screw angle was determined to be the sum of the angle formed by the screw axis and the lower and upper endplates in the LIV and UIV, respectively. The change (Δ) in the parameters from postoperative to final follow-up was calculated. The relationships between the UIV-LIV Cobb angle and other radiographic parameters were evaluated by linear regression analyses. RESULTS: Fourteen patients met the inclusion criteria. Their median age was 15.5 years, and the median follow-up period was 53.6 months. The median UIV-LIV Cobb angle was -1.4° at postoperative 1 month. The median screw angle was 4.7°, and overcorrection was achieved in 11 (79%) cases at postoperative 1 month. The screw angle (r2 = 0.42, p = 0.012) and Δ FDUV-CSVL (the deviation of the first distal uninstrumented vertebra from the central sacral vertical line, r2 = 0.53, p = 0.003) were significantly correlated with the UIV-LIV Cobb angle. CONCLUSIONS: Screw placement in the UIV and LIV not parallel to the endplate, but angled, was an effective method to facilitate overcorrection in the instrumented vertebrae. The results of the present study suggest that overcorrection could bring spontaneous improvement of coronal balance below the instrumented segment during the postoperative period.

Randomized trial of granulocyte colony-stimulating factor for spinal cord injury.

Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 µg/m2/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population.

Thoracic kyphosis in light of lumbosacral alignment in thoracic adolescent idiopathic scoliosis: recognition of thoracic hypokyphosis and therapeutic implications.

BACKGROUND: The uniqueness of spinal sagittal alignment in thoracic adolescent idiopathic scoliosis (AIS), for example, the drastically smaller thoracic kyphosis seen in some patients, has been recognized but not yet fully understood. The purpose of this study was to clarify the characteristics of sagittal alignment of thoracic AIS and to determine the contributing factors. METHODS: Whole spine radiographs of 83 thoracic AIS patients (73 females) were analyzed. The measured radiographic parameters were the Cobb angle of thoracic scoliosis, thoracic kyphosis (TK), lumbar lordosis (LL), C7 sagittal vertical axis (C7 SVA), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). Additionally, max-LL, which was defined as the maximum lordosis angle from the S1 endplate, the inflection point between thoracic kyphosis and lumbar lordosis, and the SVA of the inflection point (IP SVA) were measured. The factors significantly related to a decrease in TK were assessed by stepwise logistic regression analysis. In addition, cluster analysis was performed to classify the global sagittal alignment. RESULTS: The significant factors for a decrease in TK were an increase in SS (p = 0.0003, [OR]: 1.16) and a decrease in max-LL (p = 0.0005, [OR]: 0.89). According to the cluster analysis, the global sagittal alignment was categorized into the following three types: Type 1 (low SS, low max-LL, n = 28); Type 2 (high SS, low max-LL, n = 22); and Type 3 (high SS, high max-LL, n = 33). CONCLUSIONS: In thoracic AIS, a decreased TK corresponded to an increased SS or a decreased max-LL. The sagittal alignment of thoracic AIS patients could be classified into three types based on SS and max-LL. One of these three types includes the unique sagittal profile of very small TK.

Bi-allelic loss of function variants of TBX6 causes a spectrum of malformation of spine and rib including congenital scoliosis and spondylocostal dysostosis.

BACKGROUND: Congenital scoliosis (CS) is a common vertebral malformation. Spondylocostal dysostosis (SCD) is a rare skeletal dysplasia characterised by multiple vertebral malformations and rib anomalies. In a previous study, a compound heterozygosity for a null mutation and a risk haplotype composed by three single-nucleotide polymorphisms in TBX6 have been reported as a disease-causing model of CS. Another study identified bi-allelic missense variants in a SCD patient. The purpose of our study is to identify TBX6 variants in CS and SCD and examine their pathogenicity. METHODS: We recruited 200 patients with CS or SCD and investigated TBX6 variants. We evaluated the pathogenicity of the variants by in silico prediction and in vitro experiments. RESULTS: We identified five 16p11.2 deletions, one splice-site variant and five missense variants in 10 patients. In vitro functional assays for missense variants identified in the previous and present studies demonstrated that most of the variants caused abnormal localisation of TBX6 proteins. We confirmed mislocalisation of TBX6 proteins in presomitic mesoderm cells induced from SCD patient-derived iPS cells. In induced cells, we found decreased mRNA expressions of TBX6 and its downstream genes were involved in somite formation. All CS patients with missense variants had the risk haplotype in the opposite allele, while a SCD patient with bi-allelic missense variants did not have the haplotype. CONCLUSIONS: Our study suggests that bi-allelic loss of function variants of TBX6 cause a spectrum of phenotypes including CS and SCD, depending on the severity of the loss of TBX6 function.

Osseointegration improves bone-implant interface of pedicle screws in the growing spine: a biomechanical and histological study using an in vivo immature porcine model.

PURPOSE: Implant failure is a frequent complication in corrective surgery for early onset scoliosis, since considerable forces are acting on small and fragile vertebrae. Osseointegration showing biomechanical and histological improvement in bone-implant interface (BII) after dental implant placement has been well investigated. However, there are no studies regarding osseointegration in immature vertebral bone. The purpose was to evaluate the timecourse of biomechanical and histological changes at BII after pedicle screw placement using in vivo immature porcine model. METHODS: Ten immature porcine were instrumented with titanium pedicle screws in the thoracic spine. After a 0-, 2-, 4-, and 6-month survival periods, the spines were harvested at the age of 12 months. Histological evaluation of BII was conducted by bone volume/tissue volume (BV/TV) and bone surface/implant surface (BS/IS) measurements. Bone mineral density (BMD) measurement and biomechanical testing of BII were done. RESULTS: Contact surface and bone volume around the screw threads were significantly increased over the time. BV/TV and BS/IS were improved with statistically significant differences between 0- and ≥4-month (p ≤ 0.001) periods. BMD in all subjects was determined to be the same (p ≥ 0.350). Pullout strength was also increased over time with significant differences between 0- and ≥2-month (p ≤ 0.011) periods. CONCLUSION: Improved stability at BII caused by osseointegration was confirmed by in vivo immature porcine model. A two-stage operation is proposed based on the osseointegration theory, in which an implant is installed in advance in the vertebrae at the first stage and deformity correction surgery is performed after sufficient stability is obtained by osseointegration at a later stage.

Multiple concave rib head resection improved correction rate of posterior spine fusion in treatment of adolescent idiopathic scoliosis.

BACKGROUND: Hybrid constructs have been widely used to surgically correct thoracic adolescent idiopathic scoliosis (AIS). To enhance the correction obtained with hybrid constructs, we perform concave rib head resection and convex costovertebral release as posterior release procedures. The objective of the study was to evaluate coronal and sagittal curve correction in patients with adolescent idiopathic scoliosis (AIS) treated with hybrid constructs combined with concave rib head resection and convex transverse process resection as posterior release procedures. METHODS: The records of 24 patients with Lenke type 1 or 2 AIS treated with hybrid constructs combined with posterior release procedures were retrospectively reviewed. The mean age at surgery was 14.3 years. The mean follow-up period was 33.0 months (range, 24-60 months). Radiographs were evaluated before surgery, immediately postoperatively, and at latest follow-up. RESULTS: The average preoperative Cobb angle of the main thoracic (MT) curve was 58.1 ± 12.6° (range, 45-88°). The MT curve was corrected to 12.8 ± 9.0° (range, 0-38°) immediately after surgery. At the latest follow-up, the average Cobb angle was 13.6 ± 9.9° (range, 0-44°; correction, 77.5 ± 14.0%). The average loss of coronal correction was 0.8°. The average preoperative flexibility of the MT curve was 54.6 ± 17.4%. The average Cincinnati correction index was 1.53 ± 0.48 at the latest follow-up. The average preoperative thoracic kyphosis (TK) was 13.7 ± 12.0° (range, -12-34°). Immediately after surgery, TK was corrected to 18.6 ± 5.9° (range, 10-29°). At the latest follow-up, TK measured 18.1 ± 6.5° (range, 6-32°). CONCLUSIONS: Hybrid instrumentation combined with concave rib head resection and convex transverse process resection as posterior release procedures achieved satisfactory coronal and sagittal curve correction with little loss of correction at 2-year follow-up.

Optimum pelvic incidence minus lumbar lordosis value can be determined by individual pelvic incidence.

PURPOSE: Adult spinal deformity (ASD) classification showing that ideal pelvic incidence minus lumbar lordosis (PI-LL) value is within 10° has been received widely. But no study has focused on the optimum level of PI-LL value that reflects wide variety in PI among patients. This study was conducted to determine the optimum PI-LL value specific to an individual's PI in postoperative ASD patients. METHODS: 48 postoperative ASD patients were recruited. Spino-pelvic parameters and Oswestry Disability Index (ODI) were measured at the final follow-up. Factors associated with good clinical results were determined by stepwise multiple regression model using the ODI. The patients with ODI under the 75th percentile cutoff were designated into the "good" health related quality of life (HRQOL) group. In this group, the relationship between the PI-LL and PI was assessed by regression analysis. RESULTS: Multiple regression analysis revealed PI-LL as significant parameters associated with ODI. Thirty-six patients with an ODI <22 points (75th percentile cutoff) were categorized into a good HRQOL group, and linear regression models demonstrated the following equation: PI-LL = 0.41PI-11.12 (r = 0.45, P = 0.0059). CONCLUSIONS: On the basis of this equation, in the patients with a PI = 50°, the PI-LL is 9°. Whereas in those with a PI = 30°, the optimum PI-LL is calculated to be as low as 1°. In those with a PI = 80°, PI-LL is estimated at 22°. Consequently, an optimum PI-LL is inconsistent in that it depends on the individual PI.

Dynamic global sagittal alignment evaluated by three-dimensional gait analysis in patients with degenerative lumbar kyphoscoliosis.

PURPOSE: Sagittal vertical axis (SVA) is the most commonly used parameter for evaluating global sagittal alignment (GSA) in a static condition. However, its dynamic statuses remain unclear. The aim of this study was to evaluate dynamic GSA of degenerative lumbar kyphoscoliosis (DLKS) using three-dimensional motion analysis system (3D-MAS). METHODS: Twenty-six patients with DLKS underwent gait analysis using 3D-MAS. Static (S-) and dynamic (D-) trunk angle (TA) (the angle between the vertical axis and the line connecting C7 and S1 spinous processes) and S-sagittal trunk shift (STS) and D-STS (the distance between the two vertical lines running through C7 and S1 spinous process) were recorded during treadmill walking. Pelvic angle (PA) (the angle between the horizontal axis and the line connecting the posterior and anterior superior iliac spine) were also recorded. S-PA and D-PA represent retroversion or anteversion of the pelvis, which can be substituted for pelvic tilt. As to dynamic parameters, those at the initial five steps (Di) and the final five steps (Df) of treadmill walking were also recorded. RESULTS: The median S-TA, S-STS, and S-PA were 16.0°, 11.9 cm, and -5.5° (retroversion). The median D parameters were Di-TA/Df-TA 21.8°/26.9°; Di-STS/Df-STS 14.1/21.1 cm; and Di-PA/Df-PA 15.7°/22.8° (anteversion). All D parameters were significantly greater than S parameters (P < 0.01) and all Df parameters were also significantly worse than Di parameters (P < 0.001). Thus, compensated GSA by pelvic retroversion in static condition was lost due to anteversion change of the pelvis immediately after start of walking and worsened over time. CONCLUSION: Dynamic GSA assessment using 3D-MAS can avoid underestimation of GSA loss that is detected by static standing full-length radiography.

Safety and feasibility of intravenous administration of a single dose of allogenic-Muse cells to treat human cervical traumatic spinal cord injury: a clinical trial.

INTRODUCTION: Spinal cord injury (SCI) is a devastating injury and remains one of the largest medical and social burdens because of its intractable nature. According to the recent advances in stem cell biology, the possibility of spinal cord regeneration and functional restoration has been suggested by introducing appropriate stem cells. Multilineage-differentiating stress enduring (Muse) cells are a type of nontumorigenic endogenous reparative stem cell. The positive results of Muse cell transplantation for SCI was shown previously. As a first step for clinical application in human SCI, we conducted a clinical trial aiming to confirm the safety and feasibility of intravenously injected donor-Muse cells. METHODS: The study design of the current trial was a prospective, multicenter, nonrandomized, nonblinded, single-arm study. The clinical trial registration number was JRCT1080224764. Patients with a cervical SCI with a neurological level of injury C4 to C7 with the severity of modified Frankel classification B1 and B2 were included. A primary endpoint was set for safety and feasibility. Our protocol was approved by the PMDA, and the trial was funded by the Life Science Institute, Tokyo, Japan. The present clinical trial recruited 10 participants (8 males and 2 females) with an average age of 49.3 ± 21.2 years old. All 10 participants received a single dose of allogenic CL2020 (a total of 15 × 106 cells, 2.1-2.7 × 105 cells/kg of body weight), which is a Muse cell-based product produced from human mesenchymal stem cells, by an intravenous drip. RESULTS: There were two reported severe adverse events, both of which were determined to have no causal relationship with Muse cell treatment. The change in the ISNCSCI motor score, the activity of daily living and quality of life scores showed statistically significant improvements compared to those data at the time of CL2020 administration. CONCLUSION: In the present trial, no safety concerns were identified, and Muse cell product transplantation demonstrated good tolerability. Future clinical trials with appropriate study designs incorporating a control arm will clarify the definitive efficacy of single-dose allogenic Muse cell treatment with intravenous administration to treat SCI. TRIAL REGISTRATION: jRCT, JRCT1080224764. Registered 03 July 2019, https://jrct.niph.go.jp/latest-detail/jRCT1080224764 .

Residual Neuropathic Pain in Postoperative Patients With Cervical Ossification of Posterior Longitudinal Ligament.

STUDY DESIGN: A prospective multi-institutional observational study. OBJECTIVE: To investigate and identify risk factors for residual neuropathic pain after surgery in patients with cervical ossification of posterior longitudinal ligament (c-OPLL). SUMMARY OF BACKGROUND DATA: Patients with c-OPLL often require surgery for numbness and paralysis of the extremities; however, postoperative neuropathic pain can considerably deteriorate their quality of life. METHODS: Out of 479 patients identified from multicenter c-OPLL registries between 2014 and 2017, 292 patients who could be followed up for 2 years postoperatively were reviewed, after excluding patients with nervous system comorbidities. Demographic details; medical history; radiographic factors including the K-line, spinal canal occupancy rate of OPLL, cervical kyphosis angle, and presence of spinal cord myelomalacia; preoperative Japanese Orthopaedic Association (JOA) score; surgical procedure (fusion or decompression surgery); postoperative neurological deterioration; and the visual analogue scale for pain and numbness in the upper extremities (U/E) or trunk/lower extremities (L/E) at baseline and at 2 years postoperatively were assessed. Patients were grouped into residual and non-residual groups based on a postoperative visual analogue scale ≥40 mm. Risk factors for residual neuropathic pain were evaluated by multiple logistic regression analysis. RESULTS: The prevalence of U/E and L/E residual pain in postoperative c-OPLL patients was 51.7% and 40.4%, respectively. The U/E residual group had a poor preoperative JOA score and longer illness duration, and fusion surgery was more common in the residual group than in non-residual group. The L/E residual group was older with a poorer preoperative JOA score. On multivariate analysis, risk factors for U/E residual pain were long illness duration and poor preoperative JOA score, whereas those for L/E residual pain were age and poor preoperative JOA score. CONCLUSIONS: The risk factors for residual spinal neuropathic pain after c-OPLL surgery were age, long duration of illness, and poor preoperative JOA score. LEVEL OF EVIDENCE: IV.

Evidence of causality of low body mass index on risk of adolescent idiopathic scoliosis: a Mendelian randomization study.

Introduction: Adolescent idiopathic scoliosis (AIS) is a disorder with a three-dimensional spinal deformity and is a common disease affecting 1-5% of adolescents. AIS is also known as a complex disease involved in environmental and genetic factors. A relation between AIS and body mass index (BMI) has been epidemiologically and genetically suggested. However, the causal relationship between AIS and BMI remains to be elucidated. Material and methods: Mendelian randomization (MR) analysis was performed using summary statistics from genome-wide association studies (GWASs) of AIS (Japanese cohort, 5,327 cases, 73,884 controls; US cohort: 1,468 cases, 20,158 controls) and BMI (Biobank Japan: 173430 individual; meta-analysis of genetic investigation of anthropometric traits and UK Biobank: 806334 individuals; European Children cohort: 39620 individuals; Population Architecture using Genomics and Epidemiology: 49335 individuals). In MR analyses evaluating the effect of BMI on AIS, the association between BMI and AIS summary statistics was evaluated using the inverse-variance weighted (IVW) method, weighted median method, and Egger regression (MR-Egger) methods in Japanese. Results: Significant causality of genetically decreased BMI on risk of AIS was estimated: IVW method (Estimate (beta) [SE] = -0.56 [0.16], p = 1.8 × 10-3), weighted median method (beta = -0.56 [0.18], p = 8.5 × 10-3) and MR-Egger method (beta = -1.50 [0.43], p = 4.7 × 10-3), respectively. Consistent results were also observed when using the US AIS summary statistic in three MR methods; however, no significant causality was observed when evaluating the effect of AIS on BMI. Conclusions: Our Mendelian randomization analysis using large studies of AIS and GWAS for BMI summary statistics revealed that genetic variants contributing to low BMI have a causal effect on the onset of AIS. This result was consistent with those of epidemiological studies and would contribute to the early detection of AIS.

Identification of a Functional Susceptibility Variant for Adolescent Idiopathic Scoliosis that Upregulates Early Growth Response 1 (EGR1)-Mediated UNCX Expression.

Adolescent idiopathic scoliosis (AIS) is a serious health problem affecting 3% of live births all over the world. Many loci associated with AIS have been identified by previous genome wide association studies, but their biological implication remains mostly unclear. In this study, we evaluated the AIS-associated variants in the 7p22.3 locus by combining in silico, in vitro, and in vivo analyses. rs78148157 was located in an enhancer of UNCX, a homeobox gene and its risk allele upregulated the UNCX expression. A transcription factor, early growth response 1 (EGR1), transactivated the rs78148157-located enhancer and showed a higher binding affinity for the risk allele of rs78148157. Furthermore, zebrafish larvae with UNCX messenger RNA (mRNA) injection developed body curvature and defective neurogenesis in a dose-dependent manner. rs78148157 confers the genetic susceptibility to AIS by enhancing the EGR1-regulated UNCX expression. © 2022 American Society for Bone and Mineral Research (ASBMR).

Comparison of laminoplasty and posterior fusion surgery for cervical ossification of posterior longitudinal ligament.

This prospective multicenter study, established by the Japanese Ministry of Health, Labour and Welfare and involving 27 institutions, aimed to compare postoperative outcomes between laminoplasty (LM) and posterior fusion (PF) for cervical ossification of the posterior longitudinal ligament (OPLL), in order to address the controversy surrounding the role of instrumented fusion in cases of posterior surgical decompression for OPLL. 478 patients were considered for participation in the study; from among them, 189 (137 and 52 patients with LM and PF, respectively) were included and evaluated using the Japanese Orthopaedic Association (JOA) scores, the JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), and radiographical measurements. Basic demographic and radiographical data were reviewed, and the propensity to choose a surgical procedure was calculated. Preoperatively, there were no significant differences among the participants in terms of patient backgrounds, radiographical measurements (K-line or cervical alignment on X-ray, OPLL occupation ratio on computed tomography, increased signal intensity change on magnetic resonance imaging), or clinical status (JOA score and JOACMEQ) after adjustments. The overall risk of perioperative complications was found to be lower with LM (odds ratio [OR] 0.40, p = 0.006), and the rate of C5 palsy occurrence was significantly lower with LM (OR 0.11, p = 0.0002) than with PF. The range of motion (20.91° ± 1.05° and 9.38° ± 1.24°, p < 0.0001) in patients who had PF was significantly smaller than in those who had LM. However, multivariable logistic regression analysis showed no significant difference among the participants in JOA score, JOA recovery rate, or JOACMEQ improvement at two years. In contrast, OPLL progression was greater in the LM group than in the PF group (OR 2.73, p = 0.0002). Both LM and PF for cervical myelopathy due to OPLL had resulted in comparable postoperative outcomes at 2 years after surgery.

Prospective Investigation of Surgical Outcomes after Anterior Decompression with Fusion and Laminoplasty for the Cervical Ossification of the Posterior Longitudinal Ligament: A Propensity Score Matching Analysis.

The ideal surgical strategy for cervical ossification of the posterior longitudinal ligament (OPLL) remains controversial due to the lack of high-quality evidence. Herein, we prospectively investigated the surgical outcomes of anterior cervical decompression with fusion (ADF) and laminoplasty (LAMP) with cervical OPLL. Three hundred patients were included in this study (ADF: n = 89; LAMP: n = 211 patients), and propensity score matching yielded 67 pairs of patients with ADF and LAMP, in which clinical outcomes were compared. Crude analysis revealed that the ADF group showed greater neurological recovery in cervical Japanese Orthopedic Association scores at two years, compared with that in the LAMP group (53.1% vs. 44.3%, p = 0.037). The ratio of minimum clinically important difference (MCID) success was significantly greater in the ADF group (59.6% vs. 43.6%, p = 0.016). Multivariate analysis showed that the factors affecting MCID success were age, body mass index, duration of symptoms, and choice of ADF. In the 1:1 matched analysis, neurological improvement was more favorable in the ADF group (57.2%) compared to the LAMP group (46.8%) at two years (p = 0.049). However, perioperative complications, such as dysphagia and graft-related complications, were more common in the ADF group.

Clinical Indicators of Surgical Outcomes After Laminoplasty for Patients With Cervical Ossification of the Posterior Longitudinal Ligament: A Prospective Multicenter Study.

STUDY DESIGN: A prospective multicenter study. OBJECTIVE: This study aims to evaluate patient-reported outcomes using the Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) and clarify clinical factors that affect the therapeutic effects for patients with cervical ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: Although previous studies identified factors that affected the surgical outcomes, their assessment was mainly based on the Japanese Orthopedic Association score, which only includes neurological function. Investigating this pathology through multiple functions and quality of life (QOL) is pivotal to understanding the comprehensive clinical pictures of the cervical OPLL and its therapeutic outcomes. MATERIALS AND METHODS: This study was performed by the Japanese Multicenter Research Organization for Ossification of the Spinal Ligament. A total of 478 patients with myelopathy caused by cervical OPLL from 28 institutions were prospectively registered from 2014 to 2017 and followed up for 2 years. Of the patients, 168 received laminoplasties and fully completed questionnaires. Demographic information, imaging findings, and clinical outcomes were collected. Patients were grouped according to effective or ineffective surgical outcomes as defined by the JOACMEQ using logistic regression analyses. RESULTS: Laminoplasty resulted in functional improvement in the cervical spine and upper extremity around 40% of the patients, while QOL showed only 21.4% ( P <0.01). Multivariable analyses revealed that younger age and a postoperative decrease in arm or hand pain were correlated with significantly improved function of the upper extremities. A reduction in lower limb pain favorably affected the postoperative lower extremity function. A postoperative reduction in upper extremity pain enhanced the QOL recovery. CONCLUSIONS: Surgeons should recognize the diversity of surgical outcomes after laminoplasty and understand the necessity of pain management even after the surgery to enhance bodily functions and QOL in patients with cervical OPLL.

Impact of obesity on cervical ossification of the posterior longitudinal ligament: a nationwide prospective study.

Positive association between ossification of the posterior longitudinal ligament of the spine (OPLL) and obesity is widely recognized; however, few studies focused on the effects of obesity on treatment of cervical OPLL. The effects of obesity on surgical treatment of cervical OPLL were investigated by a Japanese nationwide, prospective study. Overall, 478 patients with cervical myelopathy due to OPLL were prospectively enrolled. To clarify the effects of obesity on the surgical treatment for cervical OPLL, patients were stratified into two groups, non-obese (< BMI 30.0 kg/m2) and obese (≥ BMI 30.0 kg/m2) groups. The mean age of the obese group was significantly younger than that of non-obese group. There were no significant differences between the two groups in other demographic information, medical history, and clinical and radiographical findings. Alternatively, the obese group had a significantly higher rate of surgical site infection (SSI) than that of non-obese group. Approach-specific analyses revealed that the SSI was significantly higher in the obese group than in the non-obese group. A logistic regression analysis revealed that age, BMI, and duration of symptoms were significant factors affecting the postoperative minimum clinically important difference success. The result of this study provides useful information for future cervical OPLL treatment.

Severity of Myelopathy is Closely Associated With Advanced Age and Signal Intensity Change in Cervical Ossification of the Posterior Longitudinal Ligament: A Prospective Nationwide Investigation.

STUDY DESIGN: Prospective, nationwide case series. OBJECTIVE: To identify preoperative factors associated with myelopathy and neurological impairment in patients with cervical ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: Various studies have reported clinical outcomes following the surgical treatment of OPLL. However, there has been no large-scale study of preoperative clinical features in patients with cervical OPLL. MATERIALS AND METHODS: Data were prospectively collected from 28 institutions nationwide in Japan. In total, 512 patients with neurological impairment caused by cervical OPLL requiring surgery were enrolled. Basic demographic and clinical data, including age, sex, diabetes status, body mass index, smoking history, and disease duration were collected. C2-7 lordotic angle, canal narrowing ratio, range of motion in flexion-extension at C2-7, and type of OPLL were evaluated on lateral radiographs to identify factors influencing the clinical features of patients with OPLL in whom surgery was planned. RESULTS: Complete documentation was available for 490 patients (362 male, 128 female). In total, 34 patients had the localized type, 181 had the segmental type, 64 had the continuous type, and 211 had the mixed type. Although there were no significant differences in age, body mass index, disease duration, Japanese Orthopedic Association (JOA) score, and lordotic angle at C2-7 according to the type of OPLL, significant differences were observed in a range of motion at C2-7 and the canal narrowing ratio among the 4 types. Multiple regression analysis revealed that the JOA score was significantly associated with age and signal intensity change on magnetic resonance imaging. CONCLUSIONS: This is the first large-scale, prospective, multicenter case series study to investigate factors influencing preoperative neurological status in patients with OPLL. Age and signal intensity change on magnetic resonance images were significantly associated with JOA score in patients requiring surgery. LEVEL OF EVIDENCE: Level II.