Environmental Factors Rather Than Genetics Likely Drive Vitamin D Deficiency in Idiopathic Scoliosis.

Abstract

Low vitamin D levels in individuals with idiopathic scoliosis (IS) have been reported and suggested as a potential contributor to IS. Bone density has also been shown to be lower in individuals with IS. To investigate serum levels of vitamin D, parathyroid hormone (PTH), markers of bone metabolism, and the genetic variation associated with vitamin D levels and bone density in individuals with IS and healthy controls. Case-control study combining Scandinavian serum cohorts and genetic cohorts. Serum analyses: 174 individuals with IS and 153 non-scoliotic controls. 1,394 individuals with IS and 11,108 controls. Serum 25-hydroxyvitamin D [25(OH)D)], PTH, C-terminal telopeptide (CTX), osteocalcin, calcium, phosphate, creatinine, albumin, ALP and leptin. Polygenic risk scores (PRS) for 25(OH)D and bone mineral density (BMD). Serum samples were analyzed using validated clinical laboratory methods. PRS for 25(OH)D and bone mineral density (BMD) were calculated based on previous literature. Statistical analyses were performed using Mann-Whitney U-tests, logistic and linear regression. Mendelian randomization was analyzed using logistic regression and the inverse-variance weighted method. In the serum cohort, median 25(OH)D levels were 54.4 nmol/L in individuals with IS and 67.0 nmol/L in controls. Corresponding PTH levels were 4.0 pmol/L and 3.2 pmol/L. No statistically significant differences were found in CTX, osteocalcin, ALP, or leptin. PRS for 25(OH)D was associated with serum 25(OH)D levels. PRS in individuals with IS and controls were non-significant for 25(OH)D, BMD femoral neck, and BMD lumbar spine. A tendency for lower values for estimated BMD heel was seen in individuals with scoliosis compared to controls. Our findings indicate altered regulation of the vitamin D-PTH axis in idiopathic scoliosis, likely driven by environmental rather than genetic factors. Bone turnover markers were comparable between groups, no clear genetically mediated BMD differences could be observed.