Idiopathic Scoliosis New Onset and Melatonin Phase Delay in Children

Melatonin Phase Delay May Increase Risk of Children and Adolescent Idiopathic Scoliosis.

This study aimed to investigate the prevalence and clinical significance of melatonin phase delay in children with new onset and progressive idiopathic scoliosis (IS).

Scoliosis is a three-dimensional (3D) structural deformity of the spine defined as a radiological lateral curvature of the spine in the coronal plane of ≥10°. The worldwide prevalence of spinal curves ranges from 0.5% to 5% in children aged 10-16 years. The aetiopathogenesis of idiopathic scoliosis includes genetic abnormalities, neuromuscular, biomechanics, bone metabolism, hormonal factors, and lifestyle explorations. However, none of these factors has been established conclusively as a direct cause of IS.

Etiological research is crucial for the treatment and prevention of idiopathic scoliosis (IS). "Melatonin deficiency" was once one of the most promising etiological hypotheses for IS. Blood melatonin deficiency and dysfunction of its signaling pathways are widely suspected to play a significant role in adolescent idiopathic scoliosis (AIS). In 1994, Machida et al were the first to discover that melatonin deficiency caused by pinealectomy could induce changes similar to idiopathic scoliosis in chickens. Bipedal mice (standing and walking on hind limbs) that underwent pinealectomy or bipedal C57BL/6 mice naturally lacking melatonin were subsequently shown to develop scoliosis as well.

However, the relationship between circulating melatonin levels and AIS in human adolescents has shown significant discrepancies among studies. Whether IS patients have a melatonin deficiency remains to be seen. While Ahuja et al found that daytime melatonin levels in AIS patients were lower than those in normal controls, most other researchers reported no significant differences in serum melatonin, urinary melatonin metabolite levels during the day and night between IS patients and controls. Goultidis et al. even found that melatonin levels in AIS patients were higher than those in the control group. Current studies only measure melatonin concentration. The impact of changes in melatonin secretion patterns on scoliosis has not yet been reported. Our cross-sectional study found that the onset and peak of melatonin secretion were both delayed in patients with scoliosis compared to the control group. The delayed melatonin secretion could be a potential cause of scoliosis.

To fill those gaps, investigators will perform a prospective, unrandomized, observational cohort study at a scoliosis center to determine the prevalence and significance of melatonin phase delay in children with IS. All subjects underwent scoliosis screening led by the Zhejiang Provincial Government. Those with a scoliometer-measured ATR > 5 degrees and a Cobb angle > 10 degrees on X-ray were diagnosed with scoliosis. Individuals with an ATR > 5 degrees but a Cobb angle < 10 degrees on X-ray, or an ATR < 5 degrees, were classified as normal. Subjects screened with the Morning and Evening Questionnaire-5 (MEQ-5), the Pediatric Sleep Questionnaire (PSQ), and the Pittsburgh Sleep Quality Index (PSQI) are used to assess circadian rhythm and sleep quality. Routine follow-up visits will be scheduled 6 months apart up to at least 36 months to assess the new onset scoliosis. Patients diagnosed with scoliosis underwent X-ray examinations, while those not diagnosed with scoliosis were uniformly screened for scoliosis in Zhejiang Province during 2024-2027

Inclusion Criteria:

• Collect saliva according to standards and complete melatonin testing

  • Complete scoliometer or X-ray assess scoliosis
  • Skeletally immature (Risser Sign 0-3)
  • Age between 6 and 15
  • Patients can understand and complete the MEQ-5, PSQ, and PSQI Questionnaire at baseline and follow-up visits
  • Informed Consent Form signed by subject or the guardian

Exclusion Criteria:

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