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.

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.

Gut Microbiota Alterations in Adolescent Idiopathic Scoliosis Are Associated with Aberrant Bone Homeostasis.

OBJECTIVE: Low bone mineral density is the major prognostic factor for adolescent idiopathic scoliosis (AIS), but the underlying mechanisms remain unclear. Accumulating evidence suggests that gut microbiota (GM) have the potential to affect bone development, and the GM signatures are altered in AIS patients. However, the effect of GM alterations on aberrant bone homeostasis in AIS remains unclear. This study aims to investigate the GM profile in AIS patients with different bone mineral density (BMD) and explore the association between GM, osteopenia, and aberrant bone turnover. METHODS: A total of 126 patients with AIS who received surgical treatment were retrospectively included in this study. We analyzed the composition of the GM by 16S rRNA sequencing and BMD by dual X-ray absorptiometry. Based on the BMD of the femur neck, the patients were divided into the osteopenia group (OPN) if the Z score < -1, and the normal (NOR) group if the Z score ≥ -1 SD compared to the healthy control. For the 16S rRNA sequencing, the raw reads were filtered to remove low-quality reads, and operational taxonomic units were identified with the Uparse program. Weighted UniFrac distance matrix for the beta-diversity metrics and principal coordinate analysis (PCoA) was performed, and the statistical comparisons were made with permutational multivariate analysis of variance (PERMANOVA) and analysis of similarity (ANONISM). Linear discriminant analysis effect size (LEfSe) was used to identify the enriched species in two groups. The "Random forest" was applied to determine the optimal biomarker for OPN according to the mean decrease in Gini value. The metabolic function was predicted by the Tax4Fun analysis. The Pearson correlation coefficient was used to evaluate the associations between GM species, bone turnover markers, and BMD. RESULTS: The serum ß-CTX was increased in the OPN group (n = 67) compared to the NOR group (n = 59). Patients in OPN groups showed significantly decreased α diversity indicated by the Shannon index. Principal coordinate analysis (PCoA) analysis showed significant clustering of GM between OPN and NOR groups. At genus level, the Escherichia-Shigella and Faecalibacterium were significantly enriched in the OPN group compared to that in the NOR group (p < 0.05), whereas the abundance of Prevotella was significantly decreased (p = 0.0012). The relative abundance of Megamonas and Prevotella was positively correlated with the femur BMD. The abundance of Escherichia-Shigella was negatively correlated with femur BMD and positively correlated with serum ß-CTX levels. Functional analysis revealed significant differences in starch and sucrose metabolism, pyruvate and cysteine, and methionine metabolism between NOR and OPN groups. CONCLUSION: The alterations of GM in AIS patients are correlated with osteopenia. The association between enriched species, BMD, and bone turnover markers provides novel diagnostic and therapeutic targets for the clinical management of AIS.

Development of ethnicity-adjusted global alignment and proportion score to predict the risk of mechanical complications following corrective surgery for adult spinal deformity.

BACKGROUND CONTEXT: Surgery for degenerative scoliosis (DS) is a complex procedure with high complication and revision rates. Based on the concept that pelvic incidence (PI) is a constant parameter, the global alignment and proportional (GAP) score was developed from sagittal alignment data collected in the Caucasian populations to predict mechanical complications. However, the PI varies among different ethnic groups, and the GAP score may not apply to Chinese populations. Thus, this study aims to assess the predictability of the GAP score for mechanical complications in the Chinese populations and develop an ethnicity-adjusted GAP score. PURPOSE: To test the predictability of the original GAP score in the Chinese population and develop a Chinese ethnicity-tailored GAP scoring system. STUDY DESIGN/SETTINGS: Retrospective cohort study. PATIENT SAMPLE: A total of 560 asymptomatic healthy volunteers were enrolled to develop Chinese ethnicity-tailored GAP (C-GAP) score and a total of 114 DS patients were enrolled to test the predictability of original GAP score and C-GAP score. OUTCOME MEASURES: Demographic information, sagittal spinopelvic parameters of healthy volunteers and DS patients were collected. Mechanical complications were recorded at a minimum of 2-year follow-up after corrective surgery for DS patients. METHODS: A total of 560 asymptomatic healthy volunteers with a mean age of 61.9±14.1 years were enrolled to develop ethnicity-adjusted GAP score. Besides, 114 surgically trated DS patients (M/F=10/104) with a mean age of 60.7±7.1 years were retrospectively reviewed. Demographic data and radiological parameters of both groups, including PI, lumbar lordosis (LL), sacral slope (SS), the sagittal vertical axis (SVA), and global tilt (GT) were collected. Ideal LL, SS, and GT were obtained by calculating their correlation with PI of healthy volunteers using linear regression analysis. Relative pelvic version (RPV), relative lumbar lordosis (RLL), lordosis distribution index (LDI), and relative spinopelvic alignment (RSA) were obtained using the ideal parameters, and the Chinese population adjusted GAP score (C-GAP) was developed based on these values. The predictability of original and C-GAP for mechanical failure was evaluated using clinical and radiological data of DS patients by evaluating the area under the curve (AUC) using receiver operating characteristic curve. This study was supported the National Natural Science Foundation of China (NSFC) (No. 82272545), ($ 8,000-10,000) and the Jiangsu Provincial Key Medical Center, and the China Postdoctoral Science Foundation (2021M701677), Level B ($ 5,000-7,000). RESULTS: Ideal SS=0.53×PI+9 (p=.002), ideal LL=0.48×PI+22 (p=.023) and ideal GT=0.46 × PI-9 (p=.011). were obtained by correlation analysis using sagittal parameters from those healthy volunteers, and RPV, RLL, RSA, and LDI were calculated accordingly. Then, the ethnicity-adjusted C-GAP score was developed by summing up the numeric value of calculated RPV, RLL, RSA, and LDI. The AUC was classified as ''no or low discriminatory power'' for the original GAP score in predicting mechanical complications (AUC=0.592, p=.078). Similarly, the original GAP score did not correlate with mechanical complications in DS patients. According to the C-GAP score, the sagittal parameters were proportional in 25 (21.9%) cases, moderately disproportional in 68 (59.6%), and severely disproportional in 21% (18.5%) cases. The incidence of mechanical complications was statistically different among proportioned and moderately disproportional and severely disproportional portions of the C-GAP score (p=.03). The predictability of the C-GAP score is high with an AUC=0.773 (p<.001). In addition, there is a linear correlation between mechanical complication rate and C-GAP score (χ=0.102, p=.02). CONCLUSION: The Ethnicity-adjusted C-GAP score system developed in the current study provided a more accurate and reliable for predicting the risk of mechanical complications after corrective surgery for adult spinal deformity.