Potential Interaction between WNT16 and Vitamin D on Bone Qualities in Adolescent Idiopathic Scoliosis Patients and Healthy Controls.

Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal deformity that is associated with low bone mineral density (BMD). Vitamin D (Vit-D) supplementation has been suggested to improve BMD in AIS, and its outcomes may be related to genetic factors. The present study aimed to (a) investigate the synergistic effect between a low BMD-related gene (wingless-related integration site 16, WNT16) and two important Vit-D pathway genes (Vit-D receptor, VDR, and Vit-D binding protein, VDBP) on serum Vit-D and bone qualities in Chinese AIS patients and healthy adolescents, and (b) to further investigate the effect of ablating Wnt16 on the cortical bone quality and whether diets with different dosages of Vit-D would further influence bone quality during the rapid growth phase in mice in the absence of Wnt16. A total of 519 girls (318 AIS vs. 201 controls) were recruited, and three selected single-nucleotide polymorphisms (SNPs) (WNT16 rs3801387, VDBP rs2282679, and VDR rs2228570) were genotyped. The serum 25(OH)Vit-D level was significantly associated with VDBP rs2282679 alleles (OR = -4.844; 95% CI, -7.521 to -2.167, p < 0.001). Significant multi-locus models were identified by generalized multifactor dimensionality reduction (GMDR) analyses on the serum 25(OH)Vit-D level (p = 0.006) and trabecular area (p = 0.044). In the gene-edited animal study, Wnt16 global knockout (KO) and wildtype (WT) male mice were provided with different Vit-D diets (control chow (1000 IU/Kg) vs. Vit-D-deficient chow (Nil in Vit-D) vs. high-dose Vit-D chow (20,000 IU/Kg)) from 4 weeks to 10 weeks old. Wnt16 global KO mice had significantly lower serum 25(OH)Vit-D levels and higher liver Vdbp mRNA expression levels than WT mice. In addition, Wnt16 global KO mice showed a decrease in bone density, cortical thickness and cortical area compared with WT mice. Interestingly, high-dose Vit-D chow led to lower bone density, cortical thickness, and cortical area in WT mice, which were less obvious in Wnt16 global KO mice. In conclusion, WNT16 may regulate the serum 25(OH)Vit-D level and bone qualities, which might be associated with VDBP expression. Further investigations with a larger sample size and wider spectrum of scoliosis severity are required to validate our findings regarding the interaction between WNT16 and Vit-D status in patients with AIS.

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.

[Trabecular bone micro-architecture in adolescent idiopathic scoliosis compared between concave and convex site of the facet joints].

OBJECTIVE: To evaluate the trabecular bone micro-structure from different sites of spine in adolescent idiopathic scoliosis patients. The target site consisted of the bilateral facet joints from apical vertebrae and from end vertebrae. METHODS: Nine AIS patients with mean age 14.9 years (range 12-17 years) and mean Cobb angle 56 degrees (ranged 48 degrees-84 degrees) were recruited into this study. Corrective surgery was indicated to these patients, and facet joint biopsies were collected during decortications for spinal fusion. Biopsy consents were obtained from patients. Bone specimens were fixed with routine histology procedures and scanned by micro computer tomography (muCT40, Scanco Medical, Switzerland). Ten pairs of facet joint were harvested from apical vertebrae and 12 pairs from end vertebrae. Three-dimensional reconstructed images with the resolution of 20 microm were achieved for histomorphometric analysis. RESULTS: The values of BV/TV (0.268 vs. 0.354, P < 0.05), TbTh (0.20 vs. 0.24, P < 0.05), TbSP (0.66 vs. 0.56, P < 0.05) and BS/BV (12.7 vs. 10.4, P < 0.05) between convex and concave side at the apex area were significantly different. No difference was found in any structural parameters between left and right side at end area, and upper thoracic (T5, 6) and thoracolumbar (T12, L1). CONCLUSION: Due to asymmetric compression and tension shared between convex and concave side, more bone and thicker and more profound trabecular bones are observed in the concave side than in the convex side, which seems to resist the progression of spinal curvature. This finding suggests that the provocative factors which cause the progression of the curve in certain patients may not lie in the bone component of spine.

Trabecular bone micro-architecture and bone mineral density in adolescent idiopathic and congenital scoliosis.

OBJECTIVE: To investigate the microstructure of trabecular bone in adolescent idiopathic scoliosis (AIS) and age-matched congenital scoliosis (CS), and to evaluate the bone mineral status of CS patients compared with normal controls and AIS patients. METHODS: This study included 15 AIS and 16 CS female patients and 35 healthy female adolescents. Corrective surgery was indicated for the AIS and CS patients, from whom iliac crest biopsies were collected during autograft harvesting, and scanned by micro-computer tomography. Bone mineral status was assessed at the lumbar and hip areas in every patient by dual energy X-ray absorptiometry (DEXA). RESULTS: Significantly lower lumbar and femoral neck bone mineral density (BMD) was found in AIS patient compared with normal controls. All BMD and bone mineral content (BMC) parameters were significantly lower in CS patients compared with age-matched normal controls. Under DEXA assessment significant associations between bone volume/tissue volume (BV/TV) and BMD values were observed. In the 3D model, BV/TV was significantly higher in AIS (19.9% ± 3.4%) than in CS (13.3% ± 3.0%, P < 0.05). Significant differences between AIS and CS were also found in trabecular thickness (Tb.Th) and bone surface/bone volume (BS/BV) (155.5 ± 54.9 µm vs. 108.1 ± 17.4 µm and 16.4% ± 3.3% vs. 22.0% ± 3.4% respectively, P < 0.05 in both). CONCLUSION: Lower bone mineral status and weak trabecular bone structure observed in AIS and CS justify further investigation of the bone mineral status in scoliosis of various etiologies.