Precocious Puberty as a Significant Risk Factor for Scoliosis: A Retrospective Cohort Study Demonstrating Synergistic Effects of GnRHa Therapy and Protective Role of Vitamin D.

Abstract

Cross-sectional and retrospective cohort study. This study aimed to investigate the impact of precocious puberty (PP) on scoliosis development and to evaluate the effects of gonadotropin-releasing hormone agonist (GnRHa) therapy and vitamin D (VitD) supplementation. The effects of precocious puberty, GnRHa therapy, and VitD supplementation on scoliosis remain unclear. The cross-sectional analysis included 5605 participants, while the retrospective cohort comprised 1575 individuals. Data on PP diagnosis, GnRHa therapy, VitD supplementation were obtained from medical records. Scoliosis was radiographically defined as a Cobb angle ≥10°. Logistic and Cox regression models were used in cross-sectional and cohort analyses, respectively, to assess the associations of PP and GnRHa therapy with scoliosis incidence. In the cross-sectional study, scoliosis prevalence was higher in the PP group compared with controls (19.2% vs. 5.6%, P<0.001), yielding an adjusted odds ratio (OR) of 3.92. Vitamin D deficiency further increased scoliosis risk (HR=2.04, P=0.003). In the longitudinal cohort, PP was associated with a 5.44-fold elevated risk of de novo scoliosis. GnRHa therapy independently increased scoliosis risk (HR=1.99, P=0.004). Conversely, VitD supplementation reduced scoliosis incidence by 51.5% among GnRHa-treated patients (HR=0.43, P<0.001). A U-shaped biphasic association was observed between estradiol levels and scoliosis risk (non-linear P<0.05). PP and GnRHa therapy synergistically increase scoliosis risk, whereas VitD co-therapy mitigates this effect. Baseline spinal surveillance and VitD supplementation are recommended for PP patients initiating GnRHa therapy. 3.