Imbalanced Skeletal Muscle Mitochondrial Proteostasis Causes Bone Loss.

Although microgravity has been implicated in osteoporosis, the precise molecular mechanism remains elusive. Here, we found that microgravity might induce mitochondrial protein buildup in skeletal muscle, alongside reduced levels of LONP1 protein. We revealed that disruptions in mitochondrial proteolysis, induced by the targeted skeletal muscle-specific deletion of the essential mitochondrial protease LONP1 or by the acute inducible deletion of muscle LONP1 in adult mice, cause reduced bone mass and compromised mechanical function. Moreover, the bone loss and weakness phenotypes were recapitulated in skeletal muscle-specific overexpressing ΔOTC mice, a known protein degraded by LONP1. Mechanistically, mitochondrial proteostasis imbalance triggered the mitochondrial unfolded protein response (UPRmt) in muscle, leading to an up-regulation of multiple myokines, including FGF21, which acts as a pro-osteoclastogenic factor. Surprisingly, this mitochondrial proteostasis stress influenced muscle-bone crosstalk independently of ATF4 in skeletal muscle. Furthermore, we established a marked association between serum FGF21 levels and bone health in humans. These findings emphasize the pivotal role of skeletal muscle mitochondrial proteostasis in responding to alterations in loading conditions and in coordinating UPRmt to modulate bone metabolism.

Conditional generative adversarial network-assisted system for radiation-free evaluation of scoliosis using a single smartphone photograph: a model development and validation study.

Background: Adolescent idiopathic scoliosis (AIS) is the most common spinal disorder in children, characterized by insidious onset and rapid progression, which can lead to severe consequences if not detected in a timely manner. Currently, the diagnosis of AIS primarily relies on X-ray imaging. However, due to limitations in healthcare access and concerns over radiation exposure, this diagnostic method cannot be widely adopted. Therefore, we have developed and validated a screening system using deep learning technology, capable of generating virtual X-ray images (VXI) from two-dimensional Red Green Blue (2D-RGB) images captured by a smartphone or camera to assist spine surgeons in the rapid, accurate, and non-invasive assessment of AIS. Methods: We included 2397 patients with AIS and 48 potential patients with AIS who visited four medical institutions in mainland China from June 11th 2014 to November 28th 2023. Participants data included standing full-spine X-ray images captured by radiology technicians and 2D-RGB images taken by spine surgeons using a camera. We developed a deep learning model based on conditional generative adversarial networks (cGAN) called Swin-pix2pix to generate VXI on retrospective training (n = 1842) and validation (n = 100) dataset, then validated the performance of VXI in quantifying the curve type and severity of AIS on retrospective internal (n = 100), external (n = 135), and prospective test datasets (n = 268). The prospective test dataset included 268 participants treated in Nanjing, China, from April 19th, 2023, to November 28th, 2023, comprising 220 patients with AIS and 48 potential patients with AIS. Their data underwent strict quality control to ensure optimal data quality and consistency. Findings: Our Swin-pix2pix model generated realistic VXI, with the mean absolute error (MAE) for predicting the main and secondary Cobb angles of AIS significantly lower than other baseline cGAN models, at 3.2° and 3.1° on prospective test dataset. The diagnostic accuracy for scoliosis severity grading exceeded that of two spine surgery experts, with accuracy of 0.93 (95% CI [0.91, 0.95]) in main curve and 0.89 (95% CI [0.87, 0.91]) in secondary curve. For main curve position and curve classification, the predictive accuracy of the Swin-pix2pix model also surpassed that of the baseline cGAN models, with accuracy of 0.93 (95% CI [0.90, 0.95]) for thoracic curve and 0.97 (95% CI [0.96, 0.98]), achieving satisfactory results on three external datasets as well. Interpretation: Our developed Swin-pix2pix model holds promise for using a single photo taken with a smartphone or camera to rapidly assess AIS curve type and severity without radiation, enabling large-scale screening. However, limited data quality and quantity, a homogeneous participant population, and rotational errors during imaging may affect the applicability and accuracy of the system, requiring further improvement in the future. Funding: National Key R&D Program of China, Natural Science Foundation of Jiangsu Province, China Postdoctoral Science Foundation, Nanjing Medical Science and Technology Development Foundation, Jiangsu Provincial Key Research and Development Program, and Jiangsu Provincial Medical Innovation Centre of Orthopedic Surgery.

Topical vancomycin powder for the prevention of surgical site infections in spinal deformity surgery: a systematic review and meta-analysis.

PURPOSE: To assess the effectiveness and safety of topical vancomycin powder (VP) in preventing surgical site infections (SSIs) in spinal deformity surgeries. METHODS: A literature search was conducted on Web of Science, PubMed, and Cochrane Library databases for comparative studies of VP in spinal deformity surgeries published before February 2024. Two reviewers independently screened eligible articles based on the inclusion and exclusion criteria, assessed study quality, and extracted data. Data analysis was performed using Review Manager 5.4 software. RESULTS: Of all 143 papers screened, a meta-analysis was conducted on 10 articles, which included a total of 8,166 surgeries. The results of the meta-analysis indicated that the incidence of deep SSI in VP group was 0.28 times that in non-VP group (p < 0.001). In the subgroup analysis, VP treatment significantly reduced the risk of deep SSI in both adult spinal deformity (ASD) (RR 0.40, 95% CI 0.21-0.77, p = 0.006) and pediatric scoliosis (PS) (RR 0.25, 95% CI 0.16-0.38, p < 0.001) surgeries. However, this effect was not observed in neuromuscular scoliosis (NMS) patients (RR 0.66, 95% CI 0.26-1.66, p = 0.38). Bacterial culture results indicated that VP treatment significantly reduced polymicrobial infections (p = 0.007) and gram-positive infections (p = 0.001). CONCLUSION: From the literature available at present, VP was associated with reduced deep SSIs rates in spinal deformity patients. However, particular attention should be paid to the lack of the effectiveness of VP in NMS patients. The current literature did not report local cytotoxicity or renal toxicity related to VP in spinal deformity patients.

Predicting postoperative mechanical complications with the ethnicity-adjusted global alignment and proportion score in degenerative scoliosis: does paraspinal muscle degeneration matter?

BACKGROUND: The global alignment and proportion (GAP) score was developed to predict mechanical complications (MCs) after adult spinal deformity surgery but showed limited sensitivity in the Asian population. Considering variations in sagittal parameters among different ethnic groups, our team developed the ethnicity-adjusted GAP score according to the spinopelvic parameters of 566 asymptomatic Chinese volunteers (C-GAP score). Notably, degenerative scoliosis (DS) patients with MCs following corrective surgery have more severe paraspinal muscle degeneration. For DS patients with various sagittal alignments, the unevenly distributed degeneration of paraspinal muscle may exert different influences on MC occurrence and largely affect the accuracy of the C-GAP score in clinical assessment. Therefore, incorporating paraspinal muscle degeneration indices within the C-GAP score may improve its accuracy in predicting MC occurrence. PURPOSE: We aimed to clarify the influence of paraspinal muscle degeneration on the C-GAP score predicting MC occurrence following DS surgery and modify the C-GAP score with paraspinal muscle degeneration parameters. STUDY DESIGN: A retrospective case-control study. SAMPLE SIZE: 107 adult degenerative scoliosis patients. OUTCOME MEASURES: Demographic information, postoperative sagittal spinopelvic parameters, the GAP score, the C-GAP score, and paraspinal muscle degeneration parameters. METHODS: A total of 107 DS patients undergoing posterior spinal fusion surgery (≥4 vertebrae) with a minimum of 2 years follow-up (or experiencing MCs within 2 years) were retrospectively reviewed. Their C-GAP score was calculated based on our previous study and patients were divided into 3 C-GAP categories, "proportioned" (P), "moderately disproportioned" (MD), and "severely disproportioned" (SD). Relative cross-sectional area (cross-sectional area of muscle-disc ratio×100, rCSA) and fat infiltration rate, FI% at L1/2, L2/3, L3/4, and L4/5 discs were quantitatively evaluated using magnetic resonance imaging (MRI). In each C-GAP category, patients were additionally divided into the MC group and the non-MC group to analyze their paraspinal muscle degeneration. A multivariable logistic regression model consisting of the CSA-weighted average FI% (total FI%) and the C-GAP score, C-GAPM was constructed. The area under the curve (AUC) of the receiver operating characteristic (ROC) curves was used to evaluate the predictability of the GAP score, the C-GAP score, FI%, and C-GAPM. This project was supported by the National Natural Science Foundation of China (No.82272545) and Special Fund of Science and Technology Plan of Jiangsu Province (No.BE2023658). RESULTS: For all 107 patients, FI% at L1/2, L2/3, L3/4, and L4/5 discs and the total FI% of the MC group (n=32) were significantly higher than those of the non-MC group (n=75). The MC rates of 3 original GAP categories, P, MD, and SD categories were 25.00% (6/24), 27.03%(10/37), and 34.78% (16/46) (χ2=0.944, p=0.624). Based on the C-GAP score, the MC rates of the P, MD, and SD categories were 11.90% (5/42), 34.69% (17/49), and 62.50% (10/16), showing significant differences (χ2=15.137, p=0.001). In the C-GAP MD category, compared with the non-MC group (n=32), the MC group (n=17) has a higher total FI% (26.16(22.95, 34.00) vs. 22.67(16.39, 27.37)), p=0.029). A similar trend was identified in the C-GAP SD category (34.79±11.56 vs. 19.00±5.17, p=0.007), but not in the C-GAP P category (25.09(22.82, 32.66) vs. 24.66(17.36, 28.63), p=0.361). The AUC of the GAP score, the C-GAP score, the total FI%, and C-GAPM were respectively 0.601, 0.722, 0.716, and 0.772. CONCLUSIONS: Paraspinal muscle degeneration exerts a significant effect on the occurrence of MC in the C-GAP MD, SD instead of P category. The integration of paraspinal muscle FI% with the C-GAP score (C-GAPM) enables a more accurate prediction of MCs following DS surgery. Surgeons should pay adequate attention to paraspinal muscle degeneration during surgical planning and postoperative management for patients in the C-GAP MD and SD categories.

Genetic Variants can Predict the Outcome of Brace Treatment in Patients With Adolescent Idiopathic Scoliosis.

STUDY DESIGN: A genetic case-control study. OBJECTIVES: To investigate the association between AIS progression-associated SNPs reported by GWAS studies and the effectiveness of brace treatment. SUMMARY OF BACKGROUND DATA: Bracing is the most effective conservative method to treat adolescent idiopathic scoliosis (AIS). Several factors have been reported to be associated with bracing failure in AIS patients. Genetic markers associated with AIS have potential prognostic value. METHODS: A retrospective cohort of AIS patients undergoing brace treatment was enrolled in this study and divided into success and failure groups based on treatment outcome. Clinical characteristics of AIS patients were documented. Candidate SNPs were selected from previous GWAS studies of AIS, which were known to be associated with curve progression and validated across diverse populations. Genotype and allele frequencies between the success and failure groups were compared using chi-square analysis. RESULTS: A total of 259 female AIS patients were included in this study, 30.5% of the well-braced patients had curve progression exceeding 5° and 69.5% of the patients undergo an improvement or progression of less than 5°. Allele C of rs10738445 (BNC2) could significantly add to the risk of bracing failure, with odds ratio of 1.59. No significant association with bracing outcomes was found for rs12946942 (SOX9/KCNJ2), rs1978060 (TBX1), rs1017861 (CHD7), and rs35333564 (MIR4300HG). CONCLUSIONS: SNP rs10738445 were significantly associated with brace treatment effectiveness. The other four SNPs were not significantly associated with the outcome of bracing. More SNPs and predictors should be included in future study to develop a more accurate predictive model for clinical application.

Prediction of proximal junctional kyphosis and failure after corrective surgery for adult spinal deformity: an MRI-based model combining bone and paraspinal muscle quality metrics.

BACKGROUND: Proximal junctional kyphosis (PJK) and proximal junctional failure (PJF) are common complications observed after adult spinal deformity (ASD) surgery and major cause for unplanned reoperations. In addition to spinal alignment, osteoporosis and paraspinal muscle (PSM) degeneration are reportedly indispensable factors that account for PJK/PJF. PURPOSE: To investigate the utility of the preoperative risk assessment model using MRI-based skeletomuscular metrics in predicting PJK and/or PJF(PJK/PJF) after ASD correction. STUDY DESIGN: Retrospective case-control study. PATIENT SAMPLE: Consecutive series of 149 patients at a single academic institution. OUTCOME MEASURES: MRI-based measurements of vertebral bone quality at upper instrumented vertebra (VBQ-U) score and fat infiltration rate (FI%) of paraspinal muscle (PSM). METHODS: We performed a retrospective analysis of patients with ASD who underwent ≥5-segment fusion. The vertebral bone quality (VBQ) scoring system was used to assess the bone quality. The PSM quality including FI% and cross-sectional area (CSA) was evaluated. Multivariate logistic regression was performed to determine potential risk factors of PJK/PJF. RESULTS: Of 149 patients who underwent ASD surgery, PJK/PJF was found in 45(30.2%). Mean VBQ-U scores were 3.45±0.64 and 3.00±0.56 for patients with and without PJK/PJF (p<.001). Mean FI% of PSM(L3/L4) was 27.9±12.8 and 20.7±13.3 for patients with and without PJK/PJF (p<.001). On multivariate analysis, the VBQ-U score and FI% of PSM were significant independent predictors of PJK/PJF. The AUC for the novel risk assessment model is 0.806, with a predictive accuracy of 86.7%. CONCLUSION: In patients undergoing ASD correction, paraspinal muscle and vertebral bone quality significantly outweigh radiographic alignment parameters in predicting PJK/PJF. The MRI-based risk assessment model offers a valuable tool for early assessing individualized risk for PJK/PJF.

Can pelvic incidence affect changes in sagittal spino-pelvic parameters between standing and sitting positions in individuals with lumbar degenerative disease?

OBJECTIVE: The aim of this study was to explore the correlation between PI and standing-to-sitting changes of the sagittal alignment in patients with lumbar degenerative diseases, and investigate the differences in posture changes among Roussouly types. METHODS: A total of 209 patients with lumbar degenerative disease were retrospectively included in this study. All the patients received lateral full body imaging in both standing and sitting positions. Sagittal parameters including SVA, OD-HA, PT, PI, PT/PI, SS, LL, TK, Upper LL (L1-L4) and Lower LL (L4-S1) were measured in both standing and sitting position, and the parameters were compared between two positions. The correlations between PI and lumbo-pelvic changes were analyzed. The postural changes were compared among different Roussouly types. RESULTS: From standing to sitting, all the parameters except PI significantly changed, including SVA, OD-HA, PT, PT/PI, SS, LL, TK, Upper LL and Lower LL. The contribution of lower LL was greater to global LL than upper LL. PI had a significant correlation with ΔPT, ΔSS, ΔLL, ΔUpper LL and ΔLower LL. From standing to sitting, type 4 patients had the most pronounced ΔPT, ΔSS and ΔLL, and ΔLower LL of types 3 and 4 were greater than that of types 1 and 2. CONCLUSIONS: In patients with degenerative disease, PI plays an important role in determining the extent of lumbo-pelvic changes from standing to sitting. Among different Roussouly types, type 4 patients have the most pronounced changes of PT, SS and LL, suggesting the relatively greater flexibility of pelvis and lumbar spine.

Posterior-only approach cervical hemivertebrectomy and short fusion with pedicle screws in young children with cervical scoliosis: case report and technical note.

PURPOSE: Cervical hemivertebrae (C3-6) causing significant osseous torticollis, head tilt and facial asymmetry are rare and complicated. Cervical hemivertebrectomy (CHVE) by a posterior-only approach was never reported because it is highly risky and its efficacy remains controversial. This study is to evaluate the feasibility and preliminary clinical outcomes of posterior-only approach for CHVE and torticollis correction in young children. METHODS: Four young children aged 5-9 years old with significant torticollis caused by cervical hemivertebrae underwent deformity correction consisting of cervical pedicle screw (CPS) placement with O-arm-based intraoperative navigation, CHVE using ultrasonic bone scalpel and short-segmental posterior instrumentation and fusion. Details of this novel technique were presented. The preliminary short-term clinical and radiographic outcomes were assessed. RESULTS: On average, the operative time was 312.5 ± 49.9 min, and the surgical blood loss was 375.0 ± 150.0 ml. The structural cervical scoliosis was corrected from 31.5 ± 7.3° to 11.0 ± 4.1°, and the average correction rate was 64.9%. Head tilt was favorably corrected from 11.0 ± 4.2° to 3.5 ± 2.6°. The shoulder balance improved from 6.3 ± 1.3° to 1.5 ± 1.9°. One case with C6 CHVE had convex side radiating nerve root pain but no sign of muscle power weakness. Full recovery was achieved one month after surgery. No other complication occurred. CONCLUSIONS: CHVE by a posterior-only approach was a feasible alternative option for the treatment of congenital cervical scoliosis. It could resect the CHV effectively and achieve satisfactory torticollis correction without additional anterior access surgery. Successful CPS placement in this child population was essentially important to enable reliable osteotomy closure and firm posterior instrumentation.

Nuclear receptor Rev-erbα alleviates intervertebral disc degeneration by recruiting NCoR-HDAC3 co-repressor and inhibiting NLRP3 inflammasome.

Intervertebral discs (IVDs) are rhythmic tissues that experience daily low-load recovery. Notably, aging and abnormal mechanical stress predispose IVDs to degeneration due to dysrhythmia-induced disordered metabolism. Meanwhile, Rev-erbα acts as a transcriptional repressor in maintaining biorhythms and homeostasis; however, its function in IVD homeostasis and degeneration remains unclear. This study assessed the relationship between low Rev-erbα expression levels and IVD degeneration. Rev-erbα deficiency accelerated needle puncture or aging-induced IVD degeneration, characterized by increased extracellular matrix (ECM) catabolism and nucleus pulposus (NP) cell apoptosis. Mechanistically, Rev-erbα knockdown in NP cells aggravated rhIL1ß-induced NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation, exacerbating the imbalanced ECM and NP cell apoptosis. Meanwhile, blocking NLRP3 inflammasome activation mitigated Rev-erbα deficiency and needle puncture-induced IVD degeneration. Particularly, Rev-erbα mediated the transcriptional repression of the NLRP3 inflammasome via the ligand heme-binding of nuclear receptor co-repressor (NCoR) and histone deacetylase 3 (HDAC3) complex. Thus, the increased expression of Rev-erbα in NP cells following short-term rhIL1ß treatment failed to inhibit NLRP3 transcription in vitro owing to heme depletion. Pharmacological activation of Rev-erbα in vivo and in vitro alleviated IVD degeneration by altering the NLRP3 inflammasome. Taken together, targeting Rev-erbα may be a potential therapeutic strategy for alleviating IVD degeneration and its related diseases.

Presence of compensatory curve predicts postoperative curve progression in congenital scoliosis after thoracolumbar hemivertebra resection and short fusion.

PURPOSE: To investigate the impact of preoperative compensatory curve on the postoperative curve progression in congenital scoliosis (CS) patients following thoracolumbar hemivertebra (HV) resection and short fusion. METHODS: This study retrospectively reviewed a consecutive cohort of patients with CS who underwent thoracolumbar HV resection and short fusion with a minimum of 2 years follow-up. According to the preoperative curve pattern, patients were divided into compensatory curve group non-compensatory curve group. Based on the postoperative coronal curve evolution, patients were further divided into the progressed group (Group P, with curve decompensation ≥ 20°) and the non-progressed group (Group NP, characterized by well-compensated curves). RESULTS: A total of 127 patients were included in this study, with 31 patients in the compensatory curve group and 96 patients in the non-compensatory curve group. The incidence of postoperative coronal curve progression was significantly higher in the compensatory curve group than that in non-compensatory curve group (35.5% vs. 13.5%, p = 0.007). In the compensatory curve group, patients who experienced postoperative curve progression showed fewer fusion segments (p = 0.001), greater preoperative UIV translation (p = 0.006), greater preoperative LIV tilt (p = 0.017), and larger postoperative UIV tilt (p < 0.001) compared with patients in group NP. Multiple logistic regression demonstrated that the shorter fusion segments and greater postoperative UIV tilt were two independent risk factors for postoperative curve progression. CONCLUSION: The presence of the compensatory curve was associated with a higher incidence of postoperative curve progression in patients with CS who underwent thoracolumbar HV resection and short fusion. Shorter fusion segments and greater postoperative UIV tilt were found to be the risk factors for postoperative curve progression.

The Role of Spinal Cord Compression in Predicting Intraoperative Neurophysiological Monitoring Events in Patients With Kyphotic Deformity: A Magnetic Resonance Imaging-Based Study.

OBJECTIVE: To establish a novel classification system for predicting the risk of intraoperative neurophysiological monitoring (IONM) events in surgically-treated patients with kyphotic deformity. METHODS: Patients with kyphotic deformity who underwent surgical correction of cervicothoracic, thoracic, or thoracolumbar kyphosis in our center from July 2005 to December 2020 were recruited. We proposed a classification system to describe the morphology of the spinal cord on T2-weighted sagittal magnetic resonance imaging: type A, circular/symmetric cord with visible cerebrospinal fluid (CSF) between the cord and vertebral body; type B, circular/oval/symmetric cord with no visible CSF between the cord and vertebral body; type C, spinal cord that is fattened/deformed by the vertebral body, with no visible CSF between the cord and vertebral body. Furthermore, based on type C, the spinal cord compression ratio (CR) < 50% was defined as the subtype C-, while the spinal cord CR ≥ 50% was defined as the subtype C+. IONM event was documented, and a comparative analysis was made to evaluate the prevalence of IONM events among patients with diverse spinal cord types. RESULTS: A total of 294 patients were reviewed, including 73 in type A; 153 in type B; 53 in subtype C- and 15 in subtype C+. Lower extremity transcranial motor-evoked potentials and/or somatosensory evoked potentials were lost intraoperatively in 41 cases (13.9%), among which 4 patients with type C showed no return of spinal cord monitoring data. The 14 subtype C+ patients (93.3%) had IONM events. Univariate logistic regression analysis showed that patients with a type C spinal cord (subtype C-: odds ratio [OR], 10.390; 95% confidence interval [CI], 2.215-48.735; p = 0.003; subtype C+, OR, 497.000; 95% CI, 42.126- 5,863.611; p < 0.001) are at significantly higher risk of a positive IONM event during deformity correction compared to those with a type A. In further multiple logistic regression analysis, the spinal cord classification (OR, 5.371; 95% CI, 2.966-9.727; p < 0.001) was confirmed as an independent risk factor for IONM events. CONCLUSION: We presented a new spinal cord classification system based on the relative position of the spinal cord and vertebrae to predict the risk of IONM events in patients with kyphotic deformity. In patients with type C spinal cord, especially those in C+ cases, it is essential to be aware of potential IONM events, and adopt standard operating procedures to facilitate neurological recovery.

The hyaluronic acid-gelatin hierarchical hydrogel for osteoporotic bone defect repairment.

Osteoporotic bone defects are serious medical problems due to their sparse bone structure, difficulty in restoration and reconstruction, and high recurrence rates, which also result in heavy economic and social burdens. Herein, we developed a hierarchical hydrogel composed of alendronate sodium (AS)/Mg2+-loaded inverse opal methylpropenylated gelatin (GelMA) hydrogel microspheres (IOHM-AS-Mgs) within methylpropenylated poly(hyaluronic acid) (HAMA) for osteoporotic bone defect treatment. The IOHM-AS-Mgs displayed good cytocompatibility and cell adhesion and strongly stimulated osteogenesis at the transcriptomic and protein levels. When this treatment was applied to the osteoporotic bone defect area, HAMA was used to fix the microspheres. The results of the microcomputed tomography (micro-CT) and histological analyses indicated that the hierarchical hydrogel had the best therapeutic effect. Therefore, this hydrogel is a new candidate for osteoporotic bone defect treatment.

Deep Learning-Based Prediction Model for the Cobb Angle in Adolescent Idiopathic Scoliosis Patients.

Scoliosis, characterized by spine deformity, is most common in adolescent idiopathic scoliosis (AIS). Manual Cobb angle measurement limitations underscore the need for automated tools. This study employed a vertebral landmark extraction method and Feedforward Neural Network (FNN) to predict scoliosis progression in 79 AIS patients. The novel intervertebral angles matrix format showcased results. The mean absolute error for the intervertebral angle progression was 1.5 degrees, while the Pearson correlation of the predicted Cobb angles was 0.86. The accuracy in classifying Cobb angles (<15°, 15-25°, 25-35°, 35-45°, >45°) was 0.85, with 0.65 sensitivity and 0.91 specificity. The FNN demonstrated superior accuracy, sensitivity, and specificity, aiding in tailored treatments for potential scoliosis progression. Addressing FNNs' over-fitting issue through strategies like "dropout" or regularization could further enhance their performance. This study presents a promising step towards automated scoliosis diagnosis and prognosis.

Prediction Model for Lumbar Curve Correction After Selective Thoracic Fusion in Lenke 1 and 2 Adolescent Idiopathic Scoliosis.

STUDY DESIGN: A retrospective study. OBJECTIVE: To identify independent risk factors and construct a prediction model for lumbar curve correction (LCC) after selective thoracic fusion (STF) in patients with Lenke 1 and 2 adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: STF has been widely applied to Lenke 1 and 2 AIS patients. However, LCC after STF is still controversial. METHODS: One hundred twenty-eight patients undergoing STF with at least 2 years of follow-up were included. Cases were divided into a high-LCC group and a low-LCC group according to a rounded-up median of 65%. Forty-nine variables were taken into account. Logistic regression was applied to identify independent predictive factors. A prediction model was established by backward stepwise regression, and its evaluation was implemented on R. RESULTS: Five parameters showed independent predictive value for low LCC: right shoulder higher before surgery (right shoulder higher versus balanced: odds ratio [OR]=0.244, P =0.014), postoperative Cobb angle of lumbar curve (LC) (OR=1.415, P =0.001, cutoff value=11°), lowest instrumented vertebra (LIV) distal to end vertebra (no vs. yes: OR=4.587, P =0.013), postoperative LIV tilt (OR=0.686, P =0.010, cutoff value=6.85°) and postoperative LIV+1 tilt (OR=1.522, P =0.005, cutoff value=6.25°). The prediction model included 6 variables: lumbar modifier, preoperative shoulder balance, postoperative Cobb angle of LC, LIV position, postoperative LIV tilt, and postoperative LIV+1 tilt. The model evaluation demonstrated satisfactory capability and stability (area under curve=0.890, 10-fold cross-validation accuracy=0.782). CONCLUSION: Preoperative shoulder balance, Cobb angle of LC, LIV position, postoperative LIV and LIV+1 tilt could be used to prognosticate LCC after STF. A model with solid prediction ability was established, which could further our understanding of LCC and assist in making clinical decisions.

Muscle-bone cross-talk through the FNIP1-TFEB-IGF2 axis is associated with bone metabolism in human and mouse.

Clinical evidence indicates a close association between muscle dysfunction and bone loss; however, the underlying mechanisms remain unclear. Here, we report that muscle dysfunction-related bone loss in humans with limb-girdle muscular dystrophy is associated with decreased expression of folliculin-interacting protein 1 (FNIP1) in muscle tissue. Supporting this finding, murine gain- and loss-of-function genetic models demonstrated that muscle-specific ablation of FNIP1 caused decreased bone mass, increased osteoclastic activity, and mechanical impairment that could be rescued by myofiber-specific expression of FNIP1. Myofiber-specific FNIP1 deficiency stimulated expression of nuclear translocation of transcription factor EB, thereby activating transcription of insulin-like growth factor 2 (Igf2) at a conserved promoter-binding site and subsequent IGF2 secretion. Muscle-derived IGF2 stimulated osteoclastogenesis through IGF2 receptor signaling. AAV9-mediated overexpression of IGF2 was sufficient to decrease bone volume and impair bone mechanical properties in mice. Further, we found that serum IGF2 concentration was negatively correlated with bone health in humans in the context of osteoporosis. Our findings elucidate a muscle-bone cross-talk mechanism bridging the gap between muscle dysfunction and bone loss. This cross-talk represents a potential target to treat musculoskeletal diseases and osteoporosis.

Posterior Corrective Surgery for Type II Congenital Kyphosis: SRS-Schwab Grade 4 Osteotomy or Vertebral Column Resection?

OBJECTIVE: Surgical decision-making for congenital kyphosis (CK) with failure of anterior segmentation (type II) has been contradictory regarding the trade-off between the pursuit of correction rate and the inherent risk of the osteotomy procedure. This study was designed to compare the clinical and radiographic measurement in type II CK underwent SRS-Schwab Grade 4 osteotomy and vertebral column resection (VCR), the most-adapted osteotomy techniques for CK, and to propose the strategy to select between the two procedures. METHODS: This retrospective observational comparative study evaluated surgical outcomes in type II CK patients underwent VCR or SRS-Schwab Grade 4 osteotomy at our institution between January 2015 and January 2020. Patients operated with VCR and SRS-Schwab Grade 4 osteotomy were allocated to Group 1 and Group 2 respectively. Radiographic parameters and SRS-22 quality of life metrics were assessed at pre-operation, post-operation, and during follow-up visits for both groups, allowing for a comprehensive comparison of surgical outcomes. RESULTS: Thirty-one patients (19 patients in Group 1 and 12 patients in Group 2) aged 16.3 ± 10.4 years were recruited. Correction of segmental kyphosis was similar between groups (51.1 ± 17.6° in Group 1 and 48.4 ± 19.8° in Group 2, p = 0.694). Group 1 had significantly longer operation time (365.9 ± 81.2 vs 221.4 ± 78.9, p < 0.001) and more estimated blood loss (975.2 ± 275.8 ml vs 725.9 ± 204.3 mL, p = 0.011). Alert event of intraoperative sensory and motor evoked potential (SEP and MEP) monitoring was observed in 1 patient of Group 2. Both groups had 1 transient post operative neurological deficit respectively. CONCLUSION: SRS-Schwab Grade 4 osteotomy was suitable for kyphotic mass when its apex is the upper unsegmented vertebrae or the neighboring disc, or when the apical vertebrae with an anterior/posterior (A/P) height ratio of vertebral body higher than 1/3. VCR is suitable when the apex is located within the unsegmented mass with its A/P height ratio lower than 1/3. Proper selection of VCR and SRS-Schwab Grade 4 osteotomy according to our strategy, could provide satisfying radiographic and clinical outcomes in type II CK patients during a minimum of 2 years follow-up. Patients undergoing VCR procedure might have longer operation time, more blood loss and higher incidence of peri- and post-operative complications.

Hyper-Selective Posterior Fusion is Recommended When the Modified S-Line is Positive in Lenke 5C Adolescent Idiopathic Scoliosis.

OBJECTIVE: Postoperative coronal decompensation and less fusion level are dilemmas and the proper selective posterior fusion (SPF) strategy should be investigated. We proposed a parameter, modified S-line, and aimed to investigate if the modified S-line could predict postoperative coronal decompensation in patients with Lenke 5C adolescent idiopathic scoliosis (AIS). METHODS: This is a retrospective radiographic study and Lenke 5C AIS patients undergoing SPF during the period from September 2017 to June 2021 were included. The modified S-line was defined as the line linking the centers of the concave-side pedicles of the upper end vertebra (UEV) and lower end vertebra (LEV) at baseline. A modified S-line tilt to the right is established as modified S-line+ (UEV being to the right of the LEV). The patients were further categorized into two groups: the Cobb to Cobb fusion group and the Cobb-1 to Cobb fusion group. Outcomes including thoracic Cobb angle, TL/L Cobb angle, coronal balance, upper instrumented vertebra (UIV) translation, lower instrumented vertebra (LIV) translation, UIV tilt, LIV tilt, LIV disc angle, thoracic apical vertebral translation, lumbar apical vertebral translation (L-AVT), L-T AVT ratio, L-T Cobb were measured at baseline, immediately after surgery, and the last follow-up. Radiographic parameters and the incidence of both proximal and distal decompensation between the two groups were compared by chi-square test. RESULTS: Among 92 patients, 48 were modified S-line+ and 44 were modified S-line-. Modified S-line+ status was identified as a risk factor for postoperative proximal decompensation (p = 0.005) during follow-up. In Cobb to Cobb group, a higher occurrence of proximal decompensation in individuals with modified S-line+ status (p = 0.001) was confirmed. Also, in the Cobb to Cobb group with baseline modified S-line+ status, patients presenting decompensation showed a significantly larger baseline of the UIV tilt and postoperative disc angle below the lower instrumented vertebra. However, In Cobb-1 group, the incidence of decompensation after surgery showed no association with baseline modified S-line tilt status (p = 0.815 and 0.540, respectively). CONCLUSION: The modified S-line could serve as an important parameter in surgical decision-making for Lenke 5C AIS patients. Cobb to Cobb SPF is not recommended with a modified S-line+ status, and the Cobb-1 to Cobb fusion may serve as a potential alternative.

Sagittal Imbalance in Degenerative Kyphosis: Prevalence and Implication on Postoperative Mechanical Failure.

BACKGROUND AND OBJECTIVES: To explore the patterns of sagittal imbalance in patients with lumbar or thoracolumbar degenerative kyphosis (DK) and determine its implication for the risk of mechanical complication (MC) after corrective surgery. METHODS: A total of 137 patients with DK who underwent corrective surgery were reviewed. The patients were divided into L group (with a kyphotic apex at L2 and below) and TL group (with kyphotic apex at L1 and above). Then, sacral slope (SS) (defined as S1 if SS > 0 in TL, or SS > 10 in L group) and sagittal vertical axis ≥ 5 cm (defined as +) were used as modifier sagittal balance. The Scoliosis Research Society (SRS)-22 questionnaire scores were analyzed, and the risk of mechanical failure was compared across groups. RESULTS: The distribution of subgroups was 38 (27.7%) in TLS1(-) group, 36 (26.3%) in TLS1(+) group, 16 (11.7%) in TLS0(-) group, and 5 (3.6%) in TLS0(+) group. For L group, the figure was 5 (3.6%) in LS1(-), 22 (16.1%) in LS1(+), 7 (5.2%) in LS0(-), and 8 (5.8%) in LS0(+). Patients in L group had significantly higher regional kyphosis, lower lumbar lordosis, and higher sagittal vertical axis, indicating a higher risk of global decompensation. The SRS function scores and pain scores were also lower in the L group compared with the TL group. At a minimum of 2 years of follow-up, χ2 test showed that the incidence of TLS0 (+), LS0 (-), and LS0 (+) had significantly higher rates of MC (>40%). In both TL and L groups, patients with MC were found to have significantly lower bone mineral density than those without. CONCLUSION: The findings decipher the distinct patterns of sagittal imbalance in severe DK patients with kyphotic apex at thoracolumbar or lumbar spine. Patients with kyphotic apex apex at L2 or below, low SS, and global imbalance showed the highest risk of postoperative mechanical failure.

The Influence of Radiographic Parameter on the S2 Alar-Iliac Screw Virtual Trajectory in Degenerative Lumbar Scoliosis Patients: A Computed Tomography Study.

OBJECTIVE: S2 alar-iliac (S2AI) screw had been widely used in the pelvic fusion for degenerative lumbar scoliosis (DLS) patients. However, whether S2AI screw trajectory was influenced by sagittal profile in DLS patients had not been comprehensively investigated. The objective of this study was to evaluate the associations between the optimal S2 alar-iliac (S2AI) screw trajectory and sagittal spinopelvic parameters in DLS patients. METHODS: Computed tomography (CT) scans of pelvis were performed in 47 DLS patients for three-dimensional reconstruction of S2AI screw trajectory from September 2019 to November 2021. Five S2AI screw trajectory parameters were measured in CT reconstruction images, including: 1) angle in the transverse plane (Tsv angle); 2) angle in the sagittal plane (Sag angle); 3) maximal screw length; 4) screw width; and 5) skin distance. The lumbar Cobb angle, lumbar apical vertebral translation (AVT); global kyphosis (GK); thoracic kyphosis (TK); lumbar lordosis (LL); sagittal vertical axis (SVA); sacral slope (SS); pelvic tilt (PT); and pelvic incidence (PI) were measured in standing X-ray films of the whole spine and pelvis. RESULTS: Both Tsv angle and Sag angle had significant positive associations with SS (p < 0.05) but negative associations with both PT (p < 0.05) and LL (p < 0.05) in all cases. Patients with SS less than 15° had both smaller Tsv angle and Sag angle than those with SS equal to or more than 15° (p < 0.05). The decreased LL would lead to the backward rotation of the pelvis, resulting in a more cephalic and less divergent trajectory of S2AI screw in DLS patients. CONCLUSIONS: For DLS patients with lumbar kyphosis, spine surgeons should avoid both excessive Tsv and Sag angles for S2AI screw insertion, especially when using free-hand technique.