Environmental factors rather than genetics likely drive vitamin D deficiency in idiopathic scoliosis

Ioannis Georgopoulos; Tian Cheng; Daniel Fell; Ane Simony; Mikkel O Andersen; Elísabet Einarsdottir; Magnus K Karlsson; Ingrid Bergström; Elias Diarbakerli; Nikos Schizas; Paul Gerdhem

doi:10.1016/j.spinee.2026.04.026

Environmental factors rather than genetics likely drive vitamin D deficiency in idiopathic scoliosis

Spine J. 2026 Apr 23:S1529-9430(26)00132-4. doi: 10.1016/j.spinee.2026.04.026. Online ahead of print.

Authors

Affiliations

¹ Department of Surgical Sciences, Orthopaedics and Hand Surgery, Uppsala University, Uppsala, Sweden; Department of Orthopaedics and Hand Surgery, Uppsala University Hospital, SE-751 85 Uppsala, Sweden. Electronic address: ioannis.georgopoulos@uu.se.
² Department of Surgical Sciences, Orthopaedics and Hand Surgery, Uppsala University, Uppsala, Sweden; Department of Orthopaedics and Hand Surgery, Uppsala University Hospital, SE-751 85 Uppsala, Sweden.
³ Department of Spinal Surgery, Nacka Hospital, Stockholm, Sweden.
⁴ Department of Regional Health Research, University of Southern Denmark, Odense, Denmark; Department of Orthopaedic Surgery, Lillebaelt Hospital, Kolding, Denmark.
⁵ Department of Spine Surgery and Research, Lillebaelt Hospital, Kolding, Denmark.
⁶ Science for Life Laboratory, Department of Gene Technology, KTH Royal Institute of Technology, Solna, Sweden.
⁷ Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Orthopaedics, Skåne University Hospital, Malmö, Sweden.
⁸ Department of Clinical Sciences and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.
⁹ Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Department of Reconstructive Orthopaedics, Karolinska University Hospital, Stockholm, Sweden.
¹⁰ Department of Surgical Sciences, Orthopaedics and Hand Surgery, Uppsala University, Uppsala, Sweden; Department of Orthopaedics and Hand Surgery, Uppsala University Hospital, SE-751 85 Uppsala, Sweden; Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

PMID: 42034124
DOI: 10.1016/j.spinee.2026.04.026

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 nonscoliotic controls.

Genetic analyses: A total of 1,394 individuals with IS and 11,108 controls.

Outcome measures: Serum 25-hydroxyvitamin D (25OHD), PTH, C-terminal telopeptide (CTX), osteocalcin, calcium, phosphate, creatinine, albumin, alkaline phosphatase, and leptin. Polygenic risk scores (PRS) for 25OHD and bone mineral density (BMD).

Methods: Serum samples were analyzed using validated clinical laboratory methods. PRS for 25OHD and 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 25OHD levels were 54.4 nmol/L in individuals with IS and 67.0 nmol/L in controls. Corresponding PTH levels were 4.0 and 3.2 pmol/L. No statistically significant differences were found in CTX, osteocalcin, alkaline phosphatase, or leptin. PRS for 25OHD was associated with serum 25OHD levels. PRS in individuals with IS and controls were nonsignificant for 25OHD, 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.

Conclusions: Our findings indicate altered regulation of the vitamin D-PTH axis in IS, likely driven by environmental rather than genetic factors. Bone turnover markers were comparable between groups; no clear genetically mediated BMD differences could be observed.

Keywords: Bone metabolism; Bone mineral density; Idiopathic scoliosis; Polygenic risk score; Serum level of 25OHD; Vitamin D.