Spine Journal - 2026-04-23 - Journal Article
Environmental Factors Rather Than Genetics Likely Drive Vitamin D Deficiency in Idiopathic Scoliosis.
Georgopoulos I, Cheng T, Fell D, Simony A, Andersen MO, Einarsdottir E, Karlsson MK, Bergström I, Diarbakerli E, Schizas N, Gerdhem P
Topics
Key Takeaway
Median 25(OH)D was 54.4 nmol/L in IS versus 67.0 nmol/L in controls, but polygenic risk scores for vitamin D and BMD did not differ between groups, implicating environmental rather than genetic drivers of vitamin D deficiency in idiopathic scoliosis.
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Summary
This Scandinavian case-control study asked whether vitamin D deficiency and reduced BMD in idiopathic scoliosis are genetically mediated or environmentally driven, using serum biomarkers and polygenic risk scores. Serum 25(OH)D was significantly lower in IS (54.4 vs 67.0 nmol/L) with compensatory PTH elevation (4.0 vs 3.2 pmol/L), but PRS for 25(OH)D, femoral neck BMD, and lumbar spine BMD showed no significant difference between IS and controls. Bone turnover markers (CTX, osteocalcin, ALP) were comparable between groups, and Mendelian randomization did not support a causal genetic link between vitamin D levels and IS.
Key Limitation
The serum cohort lacked data on sun exposure, dietary intake, and season of blood draw, preventing identification of the specific environmental factors driving the observed vitamin D deficit.
Original Abstract
BACKGROUND CONTEXT
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.
PURPOSE
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.
STUDY DESIGN/SETTING
Case-control study combining Scandinavian serum cohorts and genetic cohorts.
PATIENT SAMPLE
Serum analyses: 174 individuals with IS and 153 non-scoliotic controls.
GENETIC ANALYSES
1,394 individuals with IS and 11,108 controls.
OUTCOME MEASURES
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).
METHODS
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.
RESULTS
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.
CONCLUSION
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.