Introduction: Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis, which appears to be caused by a melatonin signalling dysfunction proved recently in osteoblasts. This pathology occurs and progresses during the time of pre-puberty and puberty growth. This period is known to be under the hormonal control and coincides with many biological changes related to the secretion of estrogens, of which estradiol (E2) is the most active. The female prevalence of AIS disease is clearly evident. Indeed, in Quebec the spine deformities considered clinically significant (at least 11° of deformity) are found in a girl:boy ratio of approximately 2:1 for reduced scoliosis, and this ratio increases to 10:1 for scoliosis of more than 30o of deformation. However, the reason for this female prevalence as well as the role of estrogens and estrogen receptors in AIS is not clear despite the fact that these hormones are known for their impact on bone and bone growth, including the spine.

The purpose of the present study was to investigate the role of E2 on the responsiveness of the AIS cells to the melatonin, to determine the expression of estrogens receptors (ERα and ERβ) in AIS tissues and to clarify the impact of estrogen receptor gene polymorphisms in the pathogenesis of AIS.

Methodology: The effects of oestrogen on the AIS osteoblasts (n=10) response to the melatonin was determined by measuring the reduction of forskolin-induced cAMP accumulation. The forskolin treated osteoblasts were incubated in the presence of increasing amounts of melatonin (10–11 to 10-5 M) with or without physiological concentrations (10-10 M) of 17-β-estradiol for 16 hours, and the intracellular cAMP measured by radio-immunoassay using Biotrak Kit. Using RT-PCR, we determined ERα and ERβ mRNA expression in osteoblasts from AIS patients (n=14). Polymorphisms of the first intron of the ERα gene, which contains the XbaI and PvuII polymorphisms, were investigated by PCR following digestion with restriction enzyme and using the genomic DNA from lymphocytes isolated from scoliotic patients (n=33). Using the restriction enzymes XbaI and PvuII, the allelic variants XX, Xx, xx, PP, Pp, and pp were identified in 33 AIS patients (uppercase letters represent absence, and lowercase letters represent presence of restriction sites).

Results: The intracellular level of cAMP was significantly increased (p< 0.01) in the presence of a physiological concentration of 17-β-estradiol (10-10 M) when compared to the level observed in the presence of melatonin alone (10-9 M) (melatonin + estradiol: 109.46 ± 20.07; melatonin 76.09 ± 12.32 (mean ± SD)). As previously described by Dr Moreau’s team, the same pattern (three type of response to melatonin) takes place in the presence of 17-β-estradiol. We observed the loss of ERβ gene expression in 8/ 14 AIS patients contrasting with ERα gene expression that was found in all AIS patients. The XbaI and PvuII polymorphisms were found in 70% (23/33) and 80% (26/33) of the cases respectively. Of the 33 cases, 21 presented both digestion sites, 24 presented PvuII digestion site (6 homozygote, 18 heterozygote) and 23 (8 homozygote, 15 heterozygote) presented XbaI digestion site. The allelic variants were found as follows: XX: n=8, Xx: n=15, xx: n=8, PP: n=6, Pp: n=18 and pp: n=6. Classified by their location in the spine, seven right thoracic, one left thoracic, one right thoracolumbar, three left thoracolumbar and nine right thoracic-left lumbar were found among the patients presenting PvuII positive polymorphism. Among the patients with XbaI positive polymorphism, six right thoracic, one left thoracic, one right thoracolumbar, three left thoracolumbar and eight right thoracic left lumbar were found.

Conclusion: These results show the antagonistic effects of the 17-β-estradiol on AIS osteoblasts response to the melatonin. Thus estrogens interference with melatonin signalling activity would act as a triggering or aggravating factor in the pathogenesis of AIS. At the molecular level, it is possible that estrogens attenuate the response of AIS cells to melatonin through the desensitization of melatonin receptors. The loss of ERβ expression in a significant number of AIS patients appears to be important for the change of the ERα/ERβ receptors ratio that consequently may perhaps alter estrogens signalling pathways. The XbaI and PvuII polymorphisms are present in a significant number of AIS patients but this was not dependant of the curve pattern. These results clearly support the interplays and crosstalk between estrogens and melatonin signalling pathways in AIS aetiopathogenesis.

Supported by the Fondation Yves Cotrel, Institut de France

The aim of this study is to compare the adulthood quality of life of subjects with adolescent idiopathic scoliosis who have had surgery to subjects without. Inclusion criteria were being operated or having not operated but having a scoliosis with a Cobb angle ≥ 35° at the last visit. Self-administered questionnaires (five) were sent to all eligible patients. A total of two hundred and four had surgery. The mean Rolland score for subjects was significantly higher for the group who had surgery. The only variable affecting physical component of the SF-36 was the alcohol consumption. The EuroQol score was predicted by the marital status, people being married having a better score. In conclusion, there is not significant difference in the quality of life in adulthood between the subjects with AIS whether they had surgery or not. Subjects who had surgery tend to be less in pain than people not operated on.

The aim of this study is to compare adulthood quality of life of patients with AIS who have had surgery to subjects without.

Overall, there is not significant difference in the quality of life in adulthood between the subjects with AIS whether they had surgery or not. Subjects who had surgery tend to be less in pain than people not operated on.

This preliminary study will help the health professionals involved with the management of patients with AIS make clinical decisions and better understand the long-term quality of life in idiopathic scoliosis.

Among the two hundred and ninety-nine AIS responding, two hundred and four had surgery and ninety-five none and their mean Cobb angle was respectively fifty-eight and forty-four degrees. All patients had a follow up more than twenty years. There was no significant difference as for sex, life status, education, working areas, alcoholism, smoking habits, chronic illness and reproductive health between the two groups. Same proportion of subjects in both groups had no back pain (≅30%); but more non-operated subjects had physiotherapy and/or chiropractic treatments (p< 0.001). The mean Rolland score for subjects was significantly higher for the group who had surgery (p = 0.02). Using multiple regression analysis, the only variable affecting physical component of the quality of life measured with the SF-36 was the alcohol consumption whereas the psychological of the SF-36 was predicted by alcohol consumption as well and the gender. The quality of life measured by the EuroQol was predicted mainly by the marital status, people being married having a better score.

The study was designed as a comparative retrospective cohort study. Subjects referred for Adolescent Idiopathic Scoliosis between 1960 and 1979 to Sainte-Justine Hospital were entered into the cohort. Inclusion criteria were being operated or having not operated but having a scoliosis with a Cobb angle ≥ 35° at the last visit.

A self-administered questionnaire was sent to all eligible patients. The questionnaires that were used were all reliable and valid. More specifically the instruments used were the Oswestry, Roland, SF-36, Quebec Back Pain Disability Scale, Scoliosis Research Society and the EuroQol-5D.