Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis that 
affects a significant number of young teenagers, mainly females (0.2-6 % of the 
population). Historically, several hypothesis were postulated to explain the 
aetiology of AIS, including genetic factors, biochemical factors, mechanics, 
neurological, muscular factors and hormonal factors. The neuroendocrine 
hypothesis involving a melatonin deficiency as the source for AIS has generated 
great interest. This hypothesis stems from the fact that experimental 
pinealectomy in chicken, and more recently in rats maintained in a bipedal mode, 
produces a scoliosis. The biological relevance of melatonin in idiopathic 
scoliosis is controversial since no significant decrease in circulating 
melatonin level has been observed in a majority of studies. Analysis of 
melatonin signal transduction in musculoskeletal tissues of AIS patients 
demonstrated for the first time a defect occurring in a cell autonomous manner 
in different cell types isolated from AIS patients suffering of the most severe 
form of that disease. These results have led to a classification of AIS patients 
in three different functional groups depending on their response to melatonin, 
suggesting that the cause of AIS involves several genes. Molecular analysis 
showed that melatonin signaling dysfunction is triggered by an increased 
phosphorylation of Gi proteins inactivating their function. This discovery has 
led to development of a first scoliosis screening assay. This test, using blood 
sample, is currently in clinical validation process in Canada and could be used 
for screening children at high risk of developing AIS.