Appropriate pelvic obliquity measurement method in Lenke type 5C adolescent idiopathic scoliosis: a preliminary study.

Background: Although pelvic obliquity (PO) is a risk factor for postoperative coronal decompensation in corrective surgery in adolescent idiopathic scoliosis (AIS), especially Lenke 5C, methods of measuring PO are controversial. This study aimed to establish an appropriate measurement method using multiplanar reconstructed computed tomography (MPR-CT) images instead of standing posteroanterior (PA) whole-spine radiographs to evaluate PO in patients with Lenke 5C AIS. Methods: This study was a retrospective cross-sectional study. Twenty-five patients who underwent corrective surgery for AIS in Osaka University Hospital from August 2014 to February 2023 were included. Cobb angle, L5 tilt, C7 plumb line to center sacral vertebral line (C7PL-CSVL), and leg length discrepancy (LLD) were measured on standing PA whole-spine radiographs preoperatively. Sacral obliquity (SO), the slope of the upper endplate of S1, and iliac obliquity (IO), the tilt of the line connecting the iliac crests, were measured on standing PA whole-spine radiographs and MPR-CT (SO/IO-X-ray, SO/IO-CT, respectively). S1 angle and S2 angle were measured on CT. Results: The mean age of the patients was 18.7±3.9 years and all of them were females. SO-X-ray and SO-CT were larger than IO-X-ray and IO-CT, respectively. SO-X-ray was highly correlated with SO-CT (r=0.838, P<0.001). L5 tilt had higher correlation with SO-CT (r=0.884, P<0.001) than with SO-X-ray (r=0.726, P=0.001) and IO-CT (r=0.550, P=0.22). L5 tilt was correlated poorly with IO-X-ray (r=0.104, P=0.69). The S1 angle was 4.5±3.5° meanwhile the S2 angle was 1.2±2.1°, the sacral deformity was mainly due to the S1 vertebral wedging. Conclusions: Given the asymmetric sacral morphology, SO is more appropriate pelvic parameter than IO to represent the sacral tilt of Lenke 5C AIS, especially when measured using CT images to overcome the poor visibility on PA whole-spine radiographs.

Multimodal Deep Learning-based Radiomics Approach for Predicting Surgical Outcomes in Patients with Cervical Ossification of the Posterior Longitudinal Ligament.

STUDY DESIGN: A retrospective analysis. OBJECTIVE: This research sought to develop a predictive model for surgical outcomes in patients with cervical ossification of the posterior longitudinal ligament (OPLL) using deep learning and machine learning (ML) techniques. SUMMARY OF BACKGROUND DATA: Determining surgical outcomes assists surgeons in communicating prognosis to patients and setting their expectations. Deep learning and ML are computational models that identify patterns from large datasets and make predictions. METHODS: Of the 482 patients, 288 patients were included in the analysis. A minimal clinically important difference (MCID) was defined as gain in Japanese Orthopaedic Association (JOA) score of 2.5 points or more. The predictive model for MCID achievement at 1 year post-surgery was constructed using patient background, clinical symptoms, and preoperative imaging features (x-ray, CT, MRI) analyzed via LightGBM and deep learning with RadImagenet. RESULTS: The median preoperative JOA score was 11.0 (IQR: 9.0-12.0), which significantly improved to 14.0 (IQR: 12.0-15.0) at 1 year after surgery (P < 0.001, Wilcoxon signed-rank test). The average improvement rate of the JOA score was 44.7%, and 60.1% of patients achieved the MCID. Our model exhibited an area under the receiver operating characteristic curve of 0.81 and the accuracy of 71.9% in predicting MCID at 1 year. Preoperative JOA score and certain preoperative imaging features were identified as the most significant factors in the predictive models. CONCLUSION: A predictive ML and deep learning model for surgical outcomes in OPLL patients is feasible, suggesting promising applications in spinal surgery. LEVEL OF EVIDENCE: 4.

Prospective Registration Study for Establishing Minimal Clinically Important Differences in Patients Undergoing Surgery for Spinal Metastases.

STUDY DESIGN: Multicenter, prospective registry study. OBJECTIVE: To clarify minimal clinically important differences (MCIDs) for surgical interventions for spinal metastases, thereby enhancing patient care by integrating quality of life (QoL) assessments with clinical outcomes. SUMMARY OF BACKGROUND DATA: Despite its proven usefulness in degenerative spinal diseases and deformities, the MCID remains unexplored regarding surgery for spinal metastases. METHODS: This study included 171 (out of 413) patients from the multicenter "Prospective Registration Study on Surgery for Metastatic Spinal Tumors" by the Japan Association of Spine Surgeons. These were evaluated preoperatively and at 6 months postoperatively using the Face scale, EuroQol-5 Dimensions-5 Levels (EQ-5D-5L), including the visual analog scale (VAS), and performance status. The MCIDs were calculated using an anchor-based method, classifying participants into the improved, unchanged, and deteriorated groups based on the Face scale scores. Focusing on the improved and unchanged groups, the change in the EQ-5D-5L values from before to after treatment was analyzed, and the cutoff value with the highest sensitivity and specificity was determined as the MCID through receiver operating characteristic curve analysis. The validity of the MCIDs was evaluated using a distribution-based calculation method for patient-reported outcomes. RESULTS: The improved, unchanged, and deteriorated groups comprised 121, 28, and 22 participants, respectively. The anchor-based MCIDs for the EQ-5D-5L index, EQ-VAS, and domains of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression were 0.21, 15.50, 1.50, 0.50, 0.50, 0.50, and 0.50, respectively; the corresponding distribution-based MCIDs were 0.17, 15,99, 0.77, 0.80, 0.78, 0.60, and 0.70, respectively. CONCLUSION: We identified MCIDs for surgical treatment of spinal metastases, providing benchmarks for future clinical research. By retrospectively examining whether the MCIDs are achieved, factors favoring their achievement and risks affecting them can be explored. This could aid in decisions on surgical candidacy and patient counseling.

Identification of unapproved orthopedic regenerative medicine: Usefulness of the Act on Safety of Regenerative Medicine.

In Japan, the Act on Safety of Regenerative Medicine regulates unapproved regenerative medicine. Other nations market regenerative medicine products, bypassing regulatory approval. To identify unapproved orthopedic regenerative medicine, we have used data based on the Act. Platelet-rich plasma was often used. The common target was the knee. Prices averaged $2,490.

Automated entry of paper-based patient-reported outcomes: Applying deep learning to the Japanese orthopaedic association back pain evaluation questionnaire.

BACKGROUND: Health-related patient-reported outcomes (HR-PROs) are crucial for assessing the quality of life among individuals experiencing low back pain. However, manual data entry from paper forms, while convenient for patients, imposes a considerable tallying burden on collectors. In this study, we developed a deep learning (DL) model capable of automatically reading these paper forms. METHODS: We employed the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, a globally recognized assessment tool for low back pain. The questionnaire comprised 25 low back pain-related multiple-choice questions and three pain-related visual analog scales (VASs). We collected 1305 forms from an academic medical center as the training set, and 483 forms from a community medical center as the test set. The performance of our DL model for multiple-choice questions was evaluated using accuracy as a categorical classification task. The performance for VASs was evaluated using the correlation coefficient and absolute error as regression tasks. RESULT: In external validation, the mean accuracy of the categorical questions was 0.997. When outputs for categorical questions with low probability (threshold: 0.9996) were excluded, the accuracy reached 1.000 for the remaining 65 % of questions. Regarding the VASs, the average of the correlation coefficients was 0.989, with the mean absolute error being 0.25. CONCLUSION: Our DL model demonstrated remarkable accuracy and correlation coefficients when automatic reading paper-based HR-PROs during external validation.

Development of patient-reported outcome for adult spinal deformity: validation study.

Adult spinal deformity (ASD) is a complex condition that combines scoliosis, kyphosis, pain, and postoperative range of motion limitation. The lack of a scale that can successfully capture this complex condition is a clinical challenge. We aimed to develop a disease-specific scale for ASD. The study included 106 patients (mean age; 68 years, 89 women) with ASD. We selected 29 questions that could be useful in assessing ASD and asked the patients to answer them. The factor analysis found two factors: the main symptom and the collateral symptom. The main symptom consisted of 10 questions and assessed activity of daily living (ADL), pain, and appearance. The collateral symptom consisted of five questions to assess ADL due to range of motion limitation. Cronbach's alpha was 0.90 and 0.84, respectively. The Spearman's correlation coefficient between the change of main symptom and satisfaction was 0.48 (p < 0.001). The effect size of Cohen's d for comparison between preoperative and postoperative scores was 1.09 in the main symptom and 0.65 in the collateral symptom. In conclusion, we have developed a validated disease-specific scale for ASD that can simultaneously evaluate the benefits and limitations of ASD surgery with enough responsiveness in clinical practice.

Early Versus Delayed Surgery for Elderly Traumatic Cervical Spinal Injury: A Nationwide Multicenter Study in Japan.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: The effectiveness of early surgery for cervical spinal injury (CSI) has been demonstrated. However, whether early surgery improves outcomes in the elderly remains unclear. This study investigated whether early surgery for CSI in elderly affects complication rates and neurological outcomes. METHODS: This retrospective multicenter study included 462 patients. We included patients with traumatic acute cervical spinal cord injury aged ≥65 years who were treated surgically, whereas patients with American Spinal Injury Association (ASIA) Impairment Scale E, those with unknown operative procedures, and those waiting for surgery for >1 month were excluded. The minimum follow-up period was 6 months. Sixty-five patients (early group, 14.1%) underwent surgical treatment within 24 hours, whereas the remaining 397 patients (85.9%) underwent surgery on a standby basis (delayed group). The propensity score-matched cohorts of 63 cases were compared. RESULTS: Patients in the early group were significantly younger, had significantly more subaxial dislocations (and fractures), tetraplegia, significantly lower ASIA motor scores, and ambulatory abilities 6 months after injury. However, no significant differences in the rate of complications, ambulatory abilities, or ASIA Impairment Scale scores 6 months after injury were observed between the matched cohorts. At 6 months after injury, 61% of the patients in the early group (25% unsupported and 36% supported) and 53% of the patients in the delayed group (34% unsupported and 19% supported) were ambulatory. CONCLUSIONS: Early surgery is possible for CSI in elderly patients as the matched cohort reveals no significant difference in complication rates and neurological or ambulatory recovery between the early and delayed surgery groups.

Influence of the timing of surgery for cervical spinal cord injury without bone injury in the elderly: A retrospective multicenter study.

BACKGROUND: Although previous studies have demonstrated the advantages of early surgery for traumatic spinal cord injury (SCI), the appropriate surgical timing for cervical SCIs (CSCIs) without bone injury remains controversial. Here, we investigated the influence of relatively early surgery within 48 h of injury on the neurological recovery of elderly patients with CSCI and no bone injury. METHODS: In this retrospective multicenter study, we reviewed data from 159 consecutive patients aged ≥65 years with CSCI without bone injury who underwent surgery in participating centers between 2010 and 2020. Patients were followed up for at least 6 months following CSCI. We divided patients into relatively early (≤48 h after CSCI, n = 24) and late surgery (>48 h after CSCI, n = 135) groups, and baseline characteristics and neurological outcomes were compared between them. Multivariate analysis was performed to identify factors associated with neurological recovery. RESULTS: The relatively early surgery group demonstrated a lower prevalence of cardiac disease, poorer baseline American Spinal Injury Association (ASIA) impairment scale grade, and lower baseline ASIA motor score (AMS) than those of the late surgery group (P < 0.030, P < 0.001, and P < 0.001, respectively). Although the AMS was lower in the relatively early surgery group at 6 months following injury (P = 0.001), greater improvement in this score from baseline to 6-months post injury was observed (P = 0.010). Multiple linear regression analysis revealed that relatively early surgery did not affect postoperative improvement in AMS, rather, lower baseline AMS was associated with better AMS improvement (P < 0.001). Delirium (P = 0.006), pneumonia (P = 0.030), and diabetes mellitus (P = 0.039) negatively influenced postoperative improvement. CONCLUSIONS: Although further validation by future studies is required, relatively early surgery did not show a positive influence on neurological recovery after CSCI without bone injury in the elderly.

Risk Factor Analysis of Surgery-related Complications in Primary Thoracic Spine Surgery for Degenerative Diseases and Characteristics of the Patients Also Undergoing Surgery on the Cervical and/or Lumbar Spine.

STUDY DESIGN: A retrospective cohort study using prospectively collected data. OBJECTIVE: This study primarily aimed to investigate the risk factors for surgery-related complications in primary thoracic spine surgery for degenerative diseases using a surgeon-maintained database. The secondary purpose was to elucidate the characteristics of surgically treated thoracic myelopathy that also required cervical and/or lumbar spine surgery in the study period. SUMMARY OF BACKGROUND DATA: Few studies reported surgical complications and the feature of tandem spinal stenosis in thoracic myelopathy in detail because of their rarity. MATERIALS AND METHODS: This study included 840 thoracic myelopathy patients undergoing primary surgery for degenerative diseases from 2012 to 2021, investigating the effects of diseases, surgical procedures, and patient demographics on postoperative neurological deterioration, dural tear, dural leakage, surgical-site infection, and postoperative hematoma. In thoracic myelopathy patients who were surgically treated and also undergoing cervical and/or lumbar surgery, we investigated the proportion, the effects of diseases, and the order and intervals between surgeries. RESULTS: Multivariate logistic regression revealed that significant risk factors ( P <0.05) for postoperative neurological deterioration were intervertebral disk herniation [odds ratio (OR): 4.59, 95% confidence interval (CI): 1.32-16.0) and degenerative spondylolisthesis (OR: 11.1, 95% CI: 2.15-57.5). Ossification of the ligamentum flavum (OR: 4.12, 95% CI: 1.92-8.86), anterior spinal fusion (OR: 41.2, 95% CI: 4.70-361), and circumferential decompression via a posterior approach (OR: 30.5, 95% CI: 2.27-410) were risk factors for dural tear. In thoracic myelopathy patients surgically treated, 37.0% also underwent degenerative cervical and/or lumbar surgery. CONCLUSIONS: Pathologies involving anterior decompression and instability increased the risk of postoperative neurological deterioration. The risk of dural tear was increased when dura mater adhesions were likely to be directly operated upon. It should be recognized that a relatively high proportion (37.0%) of surgically treated thoracic myelopathy patients also underwent cervical and/or lumbar surgery.

A synthetic retinoic acid receptor γ antagonist (7C)-loaded nanoparticle enhances bone morphogenetic protein-induced bone regeneration in a rat spinal fusion model.

BACKGROUND CONTEXT: Bone morphogenetic proteins (BMPs) have potent osteoinductivity and have been applied clinically for challenging musculoskeletal conditions. However, the supraphysiological doses of BMPs used in clinical settings cause various side effects that prevent widespread use, and therefore the BMP dosage needs to be reduced. PURPOSE: To address this problem, we synthesized 7C, a retinoic acid receptor γ antagonist-loaded nanoparticle (NP), and investigated its potential application in BMP-based bone regeneration therapy using a rat spinal fusion model. STUDY DESIGN: An experimental animal study. METHODS: Fifty-three male 8-week-old Sprague-Dawley rats underwent posterolateral spinal fusion and were divided into the following five treatment groups: (1) no recombinant human (rh)BMP-2 and blank-NP (Control), (2) no rhBMP-2 and 1 µg 7C-NP (7C group), (3) low-dose rhBMP-2 (0.5 µg) and 1 µg blank-NP (L-BMP group), (4) low-dose rhBMP-2 (0.5 µg) and 1 µg 7C-NP (L-BMP + 7C group), and (5) high-dose rhBMP-2 (5.0 µg) and 1 µg blank-NP (H-BMP group). Micro-computed tomography and histologic analysis were performed 2 and 6 weeks after the surgery. RESULTS: The spinal fusion rates of the Control and 7C groups were both 0%, and those of the L-BMP, L-BMP + 7C, and H-BMP groups were 55.6%, 94.4%, and 100%, respectively. The L-BMP + 7C group markedly promoted cartilaginous tissue formation during BMP-induced endochondral bone formation that resulted in a significantly better spinal fusion rate and bone formation than in the L-BMP group. Although spinal fusion was slower in the L-BMP + 7C group, the L-BMP + 7C group formed a spinal fusion mass with better bone quality than the spinal fusion mass in the H-BMP group. CONCLUSIONS: The combined use of 7C-NP with rhBMP-2 in a rat posterolateral lumbar fusion model increased spinal fusion rate and new bone volume without deteriorating the quality of newly formed bone. CLINICAL SIGNIFICANCE: 7C-NP potentiates BMP-2-induced bone regeneration and has the potential for efficient bone regeneration with low-dose BMP-2, which can reduce the dose-dependent side effects of BMP-2 in clinical settings.

A nationwide multicenter study of the cost effectiveness of five leading drugs for pharmacological management of cervicobrachial symptoms.

BACKGROUND: Cervicobrachial pain frequently affects the quality of life (QOL) of the general public and has a significant economic impact on the health care systems of various countries. There are a number of treatment options for this disease, including widely-used drug therapy, but the effectiveness of each option is indeterminate, and there have been no published cost-effectiveness analysis studies so far. This prospective observational study aimed to examine the cost-effectiveness of drug treatment for cervicobrachial symptoms. METHODS: A 6-month medication regimen for each of five frequently-prescribed drugs for cervicobrachial symptoms was administered to 322 patients at 24 centers in Japan. Outcome measures, including of the EuroQol Group 5D, Short Form-8, and Visual Analog Scale (VAS), were investigated at baseline and every month thereafter. Incremental cost-effectiveness ratios (ICERs) of the drug cost to quality-adjusted life years (QALYs) were calculated. A stratified analysis of patient characteristics was also performed to identify baseline factors potentially affecting cost-effectiveness. RESULTS: The ICER of entire drug treatment for cervicobrachial symptoms was 7,491,640 yen. Compared with the reference willingness-to-pay, the ICER was assumed to not be cost-effective. A certain number of QALYs were gained during the first 3 months after the treatment intervention, but almost no QALYs were gained during the following 3 months. Stratified analysis showed that cost-effectiveness was extremely low for patients with high baseline VAS and high QOL. CONCLUSIONS: The available medications for cervicobrachial symptoms did not have excellent cost-effectiveness. Although a certain number of QALYs were gained during the first 3 months after medication, no QALYs were gained in the latter half of the study period, suggesting that it is not advisable to continue the medication needlessly. LEVEL OF EVIDENCE: II, prospective cohort study.

Hangman's Fracture in Geriatric Population: A Nationwide Multicenter Study in Japan.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To investigate the treatments of the geriatric population with hangman's fractures using a multicenter database under the Japan Association of Spine Surgeons with Ambition (JASA). METHODS: The multicenter database included data from 1512 patients. We employed the Levine and Edwards classification for categorizing hangman's fractures. The study incorporated epidemiological data, including the prevalence of hangman's fractures, patient age, and follow-up duration. Bony fusion rates and length of hospitalization were recorded for Type I and Type II fractures, and the degree of neurological impairment was assessed. RESULTS: Hangman's fractures represented 62 cases, accounting for 7.4% of all cervical spine injuries. The patients had an average age of 76.6 ± 6.5 years, and the mean duration of follow-up was 21.5 ± 23.6 months. The study found that the bony fusion rate for hangman's fractures in the geriatric population was 88.9%. Surgical treatment was associated with a shorter hospitalization period for Type II fractures compared to conservative treatment. Thirteen cases of hangman's fractures in the geriatric population, accounting for 21%, were complicated by spinal cord injury. CONCLUSIONS: This is the largest study to date on hangman's fractures in geriatric population ≥65 years. Type I and Type II fractures, according to the Levine and Edwards classification, had a bony fusion rate of up to 90%. In patients with Type II fractures, surgical treatment led to a shorter initial hospital stay. Geriatric patients are at risk of spinal cord injury due to hangman's fractures.

A pilot study: Nano-hydroxyapatite-PEG/PLA containing low dose rhBMP2 stimulates proliferation and osteogenic differentiation of human bone marrow derived mesenchymal stem cells.

Background: Bone morphogenetic protein 2 (BMP2) can enhance posterolateral spinal fusion (PLSF). The minimum effective dose that may stimulate mesenchymal stem cells however remains unknown. Nano-hydroxyapatite (nHAp) polyethylene glycol (PEG)/polylactic acid (PLA) was combined with recombinant human BMP2 (rhBMP2). We in vitro evaluated proliferation, differentiation, and osteogenic genes of human bone marrow mesenchymal stem cells with 0.5, 1.0, and 3.0 µg/mL rhBMP2 doses in this study. Methods: In vitro experimental study was designed to proliferation by a real-time quantitative cell analysis system and the osteogenic differentiation by alkaline phosphatase (ALP) activity and osteogenic marker (Runx2, OPN, and OCN) gene expressions of human derived bone marrow mesenchymal stem cells (hBMMSCs). nHAp was produced by wet chemical process and characterized by Fourier transform infrared spectrophotometer, scanning electron microscopy, and energy-dispersive x-ray spectroscopy. PEG/PLA polymer was produced at a 51:49 molar ratio. 0.5, 1.0, and 3.0 µg/mL rhBMP2 and nHAp was combined with the polymers. hBMMSCs were characterized by multipotency assays and surface markers were assessed by flow cytometer. The hBMMSC-rhBMP2 containing nHAp-PEG/PLA composite interaction was evaluated by transmission electron microscopy. Proliferative effect was evaluated by real-time proliferation analysis, and osteogenic capacity was evaluated by ALP activity assay and qPCR. Results: hBMMSC proliferation in the 0.5 µg/mL rhBMP2 + nHAp-PEG/PLA and the 1.0 µg/mL rhBMP2 + nHAp-PEG/PLA groups were higher compared to control. 1.0 µg/mL rhBMP2 + nHAp-PEG/PLA and 3.0 µg/mL rhBMP2 + nHAp-PEG/PLA containing composites induced ALP activity on days 3 and 10. 0.5 µg/mL rhBMP2 + nHAp-PEG/PLA application stimulated Runx2 and OPN gene expressions. Conclusion: rhBMP2 + nHAp-PEG/PLA composites stimulate hBMMSC proliferation and differentiation. The nHAp-PEG/PLA composite with low dose of rhBMP2 may enhance bone formation in future clinical PLSF applications.

Bimodal artificial intelligence using TabNet for differentiating spinal cord tumors-Integration of patient background information and images.

We proposed a bimodal artificial intelligence that integrates patient information with images to diagnose spinal cord tumors. Our model combines TabNet, a state-of-the-art deep learning model for tabular data for patient information, and a convolutional neural network for images. As training data, we collected 259 spinal tumor patients (158 for schwannoma and 101 for meningioma). We compared the performance of the image-only unimodal model, table-only unimodal model, bimodal model using a gradient-boosting decision tree, and bimodal model using TabNet. Our proposed bimodal model using TabNet performed best (area under the receiver-operating characteristic curve [AUROC]: 0.91) in the training data and significantly outperformed the physicians' performance. In the external validation using 62 cases from the other two facilities, our bimodal model showed an AUROC of 0.92, proving the robustness of the model. The bimodal analysis using TabNet was effective for differentiating spinal tumors.

What Types of Strategies Are Effective in Lumbar Spine Surgery? Considering the Etiology, Imaging Findings, and Risk of Complications.

Lumbar spine surgery is commonly performed worldwide for the treatment of lumbar spinal disorder, and the surgery saves many patients with lower back and lower extremity pain [...].

Genetic insights into ossification of the posterior longitudinal ligament of the spine.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is an intractable disease leading to severe neurological deficits. Its etiology and pathogenesis are primarily unknown. The relationship between OPLL and comorbidities, especially type 2 diabetes (T2D) and high body mass index (BMI), has been the focus of attention; however, no trait has been proven to have a causal relationship. We conducted a meta-analysis of genome-wide association studies (GWASs) using 22,016 Japanese individuals and identified 14 significant loci, 8 of which were previously unreported. We then conducted a gene-based association analysis and a transcriptome-wide Mendelian randomization approach and identified three candidate genes for each. Partitioning heritability enrichment analyses observed significant enrichment of the polygenic signals in the active enhancers of the connective/bone cell group, especially H3K27ac in chondrogenic differentiation cells, as well as the immune/hematopoietic cell group. Single-cell RNA sequencing of Achilles tendon cells from a mouse Achilles tendon ossification model confirmed the expression of genes in GWAS and post-GWAS analyses in mesenchymal and immune cells. Genetic correlations with 96 complex traits showed positive correlations with T2D and BMI and a negative correlation with cerebral aneurysm. Mendelian randomization analysis demonstrated a significant causal effect of increased BMI and high bone mineral density on OPLL. We evaluated the clinical images in detail and classified OPLL into cervical, thoracic, and the other types. GWAS subanalyses identified subtype-specific signals. A polygenic risk score for BMI demonstrated that the effect of BMI was particularly strong in thoracic OPLL. Our study provides genetic insight into the etiology and pathogenesis of OPLL and is expected to serve as a basis for future treatment development.

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.

Worsening ambulation in elderly patients with cervical odontoid fractures: A nationwide multicenter study in Japan.

BACKGROUND: Despite the increasing prevalence of cervical odontoid fractures in older adults, the treatment strategy is controversial. The objectives of the current study are to investigate the prognosis and complications of cervical odontoid fractures in elderly patients and to identify factors associated with worsening of ambulation after 6 months. METHODS: This multicenter, retrospective study included 167 patients aged 65 years or older with odontoid fractures. Patient demographic and treatment data were investigated and compared according to the treatment strategy. To determine associations with worsening ambulation after 6 months, we focused on the treatment strategies (nonsurgical treatment [collar immobilization or halo vest], conversion to surgery, or initial surgery) and patients' background. RESULTS: Patients who received nonsurgical treatment were significantly older, and patients who underwent surgery had more Anderson-D'Alonzo type 2 fractures. Of the patients initially treated nonsurgically, 26% later underwent surgery. Numbers of complications, including death, and degrees of ambulation after 6 months did not differ significantly among treatment strategies. Patients who had worsened ambulation after 6 months were significantly more likely to be older than 80 years, to have needed assistance with walking before injury, and to have cerebrovascular disease. Multivariable analysis showed that a score of ≥2 on the 5-item modified frailty index (mFI-5) was significantly associated with worsening ambulation. CONCLUSIONS: Preinjury mFI-5 scores of ≥2 were significantly associated with worsening ambulation 6 months after treatment of cervical odontoid fractures in older adults.

Preoperative Symptom Duration Influences Neurological Recovery and Patient-Reported Outcome Measures After Surgical Treatment of Cervical Ossification of the Posterior Longitudinal Ligament.

STUDY DESIGN: A prospective multicenter study. OBJECTIVE: To investigate the effect of preoperative symptom duration on neurological recovery for the treatment of cervical ossification of the posterior longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: The optimal timing to perform surgery in the setting of cervical OPLL remains unknown. It is important to know the influence of symptom duration on postoperative outcomes to facilitate discussions regarding the timing of surgery. PATIENTS AND METHODS: The study included 395 patients (291 men and 104 women; mean age, 63.7 ± 11.4 yr): 204 were treated with laminoplasty, 90 with posterior decompression and fusion, 85 with anterior decompression and fusion, and 16 with other procedures. The Japanese Orthopedic Association (JOA) score and patient-reported outcomes of the JOA Cervical Myelopathy Evaluation Questionnaire were used to assess clinical outcomes preoperatively and 2 years after surgery. Logistic regression analysis was used to identify factors associated with the achievement of minimum clinically important difference (MCID) after surgery. RESULTS: The recovery rate was significantly lower in the group with symptom duration of ≥5 years compared with the groups with durations of <0.5 years, 0.5 to 1 year, and 1 to 2 years. Improvement of JOA Cervical Myelopathy Evaluation Questionnaire in the upper extremity function score ( P < 0.001), lower extremity function ( P = 0.039), quality of life ( P = 0.053), and bladder function ( P = 0.034) were all decreased when the symptom duration exceeded 2 years. Duration of symptoms ( P = 0.001), age ( P < 0.001), and body mass index ( P < 0.001) were significantly associated with the achievement of MCID. The cutoff value we established for symptom duration was 23 months (area under the curve, 0.616; sensitivity, 67.4%; specificity, 53.5%). CONCLUSIONS: Symptom duration had a significant impact on neurological recovery and patient-reported outcome measures in this series of patients undergoing surgery for cervical OPLL. Patients with symptom duration exceeding 23 months may be at greater risk of failing to achieve MCID after surgery. LEVEL OF EVIDENCE: 3.