Potential Interaction Between 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, ) and two important Vit-D pathway genes (Vit-D receptor, and Vit-D binding protein, ) on serum Vit-D and bone qualities in Chinese AIS patients and healthy adolescents, and (b) to further investigate the effect of ablating 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 . A total of 519 girls (318 AIS vs. 201 controls) were recruited, and three selected single-nucleotide polymorphisms (SNPs) ( rs3801387, rs2282679, and rs2228570) were genotyped. The serum 25(OH)Vit-D level was significantly associated with rs2282679 alleles (OR = -4.844; 95% CI, -7.521 to -2.167, < 0.001). Significant multi-locus models were identified by generalized multifactor dimensionality reduction (GMDR) analyses on the serum 25(OH)Vit-D level ( = 0.006) and trabecular area ( = 0.044). In the gene-edited animal study, 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. global KO mice had significantly lower serum 25(OH)Vit-D levels and higher liver mRNA expression levels than WT mice. In addition, 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 global KO mice. In conclusion, may regulate the serum 25(OH)Vit-D level and bone qualities, which might be associated with expression. Further investigations with a larger sample size and wider spectrum of scoliosis severity are required to validate our findings regarding the interaction between and Vit-D status in patients with AIS.