This is the first study demonstrating the presence of abnormal leptin bioavailability in AIS girls that might play an important role in the etiopathogenesis of AIS. Further investigation is required to provide a better understanding of the underlying mechanisms, with the aim to explore the potential clinical application as a biomarker for predicting curve initiation or progression in AIS.

Melatonin signaling dysfunction has been associated with the etiology of adolescent idiopathic scoliosis (AIS). Genetic analysis has also associated the occurrence of AIS with the MT2 gene. Thus, we determined whether there is abnormality in the protein expression of melatonin receptors (MT) in AIS osteoblasts. In this study, we recruited 11 girls with severe AIS and eight normal subjects for intraoperative bone biopsies. MT1 and MT2 receptor protein expressions in the isolated osteoblasts were detected. Also, cell proliferation assay using different melatonin concentrations (0, 10(-9), 10(-5), 10(-4) m) was carried out. The results showed that both MT1 and MT2 receptors are expressed in osteoblasts of the controls. While MT1 receptors were expressed in osteoblasts of all AIS subjects, osteoblasts of only 7 of 11 AIS showed expression of MT2 receptors. Melatonin stimulated control osteoblasts to proliferate. However, proliferation of AIS osteoblasts without expression of MT2 receptor, after treatment with melatonin, was minimal when compared with control and AIS osteoblasts with MT2 receptor expression. The proliferation of AIS osteoblasts with MT2 receptor was greater than those without. This is the first report demonstrating a difference between AIS and normal osteoblasts in the protein expression of MT2 receptor. The results suggest that there is a possible functional effect of MT2 receptor on osteoblast proliferation. AIS osteoblasts without expression of MT2 receptor showed the lowest percentage of viable cells after melatonin treatment. This possibly indicates the modulating role of melatonin through MT2 receptor on the proliferation of osteoblasts.

The development of scoliosis in animal models after inducing asymmetric rib growth suggests the possible role of asymmetric rib growth in the etiopathogenesis of adolescent idiopathic scoliosis (AIS). Asymmetric rib length is well recognized in idiopathic scoliosis; however, whether this rib asymmetry is primary or secondary has not been clearly documented. The objectives of this study were to investigate any rib length asymmetry in patients with AIS and compare those with scoliosis with syringomyelia (SS) with the intention of elucidating any relationship between rib growth and pathogenesis of AIS. Forty-eight AIS and 29 SS with apical vertebrae located between T7 and T9 were recruited. The average age was 13.5 ± 2.3 versus 12.5 ± 3.4 years, and the average Cobb angle of thoracic curve was 43.3° ± 16.4° versus 45.6° ± 22.6° in patients with AIS or SS, respectively. The length of all ribs was measured from the tip of costal head to the end of the same rib by built-in software on spiral computed tomography. At the levels of the apical vertebrae, the vertebrae above and below the apex, the mean discrepancy in rib length (concave minus convex rib) was 7, 4 and 7 mm, respectively, in AIS group (p < 0.01), and 6, 5 and 7 mm in SS group, respectively (p < 0.01). The rib length discrepancy between concave and convex sides was significantly correlated with the magnitude of the Cobb angle of thoracic curve in both AIS and SS groups (p < 0.01). Similar findings of the asymmetry of rib length in both AIS and SS patients pointed strongly to the fact that the rib length asymmetry in apical region is most likely secondary to the scoliosis deformity rather than playing a primary role in the etiopathogenesis.

The defect of the melatonin signaling pathway has been proposed to be one of the key etiopathogenic factors in adolescent idiopathic scoliosis (AIS). A previous report showed that melatonin receptor, MT2, was undetectable in some AIS girls. The present study aimed to investigate whether the abnormal MT2 expression in AIS is quantitative or qualitative. Cultured osteoblasts were obtained from 41 AIS girls and nine normal controls. Semi-quantification of protein expression by Western blot and mRNA expression by TaqMan real-time PCR for both MT1 and MT2 were performed. Anthropometric parameters were also compared and correlated with the protein expression and mRNA expression of the receptors. The results showed significantly lower protein and mRNA expression of MT2 in AIS girls compared with that in normal controls (p = 0.02 and p = 0.019, respectively). No differences were found in the expression of MT1. When dichotomizing the AIS girls according to their MT2 expression, the group with low expression was found to have a significantly longer arm span (p = 0.036). The results of this study showed for the first time a quantitative change of MT2 in AIS that was also correlated with abnormal arm span as part of abnormal systemic skeletal growth.