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Background: The historical view of scoliosis as a primary rotation deformity led to debate about the pathomechanic role of paravertebral muscles; particularly multifidus, thought by some to be scoliogenic, counteracting, uncertain, or unimportant. Here, we address lateral lumbar curves (LLC) and suggest a pathomechanic role for quadrates lumborum, (QL) in the light of a new finding, namely of 12th rib bilateral length asymmetry associated with idiopathic and small non-scoliosis LLC., Methods: Group 1: The postero-anterior spinal radiographs of 14 children (girls 9, boys 5) aged 9-18, median age 13 years, with right lumbar idiopathic scoliosis (IS) and right LLC less that 10°, were studied. The mean Cobb angle was 12° (range 5-22°). Group 2: In 28 children (girls 17, boys 11) with straight spines, postero-anterior spinal radiographs were evaluated similarly to the children with the LLC, aged 8-17, median age 13 years. The ratio of the right/left 12th rib lengths and it's reliability was calculated. The difference of the ratio between the two groups was tested; and the correlation between the ratio and the Cobb angle estimated. Statistical analysis was done using the SPSS package., Results: The ratio's reliability study showed intra-observer +/-0,036 and the inter-observer error +/-0,042 respectively in terms of 95 % confidence limit of the error of measurements. The 12th rib was longer on the side of the curve convexity in 12 children with LLC and equal in two patients with lumbar scoliosis. The 12th rib ratios of the children with lumbar curve were statistically significantly greater than in those with straight spines. The correlation of the 12th rib ratio with Cobb angle was statistically significant. The 12th thoracic vertebrae show no axial rotation (or minimal) in the LLC and no rotation in the straight spine group., Conclusions: It is not possible, at present, to determine whether the 12th convex rib lengthening is congenitally lengthened, induced mechanically, or both. Several small muscles are attached to the 12th ribs. We focus attention here on the largest of these muscles namely, QL. It has attachments to the pelvis, 12th ribs and transverse processes of lumbar vertebrae as origins and as insertions. Given increased muscle activity on the lumbar curve convexity and similar to the interpretations of earlier workers outlined above, we suggest two hypotheses, relatively increased activity of the right QL muscle causes the LLCs (first hypothesis); or counteracts the lumbar curvature as part of the body's attempt to compensate for the curvature (second hypothesis). These hypotheses may be tested by electrical stimulation studies of QL muscles in subjects with lumbar IS by revealing respectively curve worsening or correction. We suggest that one mechanism leading to relatively increased length of the right 12 ribs is mechanotransduction in accordance with Wolff's and Pauwels Laws.

This paper formulates a novel multifactorial Cascade Concept for the pathogenesis of adolescent idiopathic scoliosis (AIS). This Concept stems from the longitudinal findings of Clark et al. (J Bone Miner Res 29(8):1729-36, 2014) who identified leptin body composition factors at 10 years of age associated with a scoliosis deformity found at 15 years. We interpret these findings in the light of some concepts for AIS pathogenesis. In particular, we speculate that the leptin body composition effect is linked to central nervous system development and the initiation of the asynchronous neuro-osseous growth mechanism that involves the creation of a neuraxis tether of relative anterior vertebral overgrowth. The latter mechanism in combination with age and gender-related anatomical variants of vertebral backward tilt (dorsal shear concept), human upright posture, adolescent growth factors, Hueter-Volkmann effect in vertebrae and vertebral bone mass abnormalities, lead to AIS, possibly both initiation and progression of scoliosis curvatures. Being multifactorial, while the Cascade Concept cannot be tested for all its components, some components should be testable by the method of numerical simulation. Clark et al. (J Bone Miner Res 29(8):1729-36, 2014) also suggested the origin of scoliosis was in the embryonic stages of life from cell types, including adipocytes and osteoblasts, derived from the same progenitor cells, and myoblasts from mesodermal somites. The involvement of cell types from different developmental origins suggests a process acting in embryonic life at a similar time, probably environmental, as previously proposed from anthropometric studies. As a Complex disease, AIS will involve genetic, environmental and life style factors operating in development and growth; this possibility needs evaluating in epidemiological studies.

Adolescent idiopathic scoliosis (AIS) is the most common form of structural spinal deformities that have a radiological lateral Cobb angle - a measure of spinal curvature - of ≥10(°). AIS affects between 1% and 4% of adolescents in the early stages of puberty and is more common in young women than in young men. The condition occurs in otherwise healthy individuals and currently has no recognizable cause. In the past few decades, considerable progress has been made towards understanding the clinical patterns and the three-dimensional pathoanatomy of AIS. Advances in biomechanics and technology and their clinical application, supported by limited evidence-based research, have led to improvements in the safety and outcomes of surgical and non-surgical treatments. However, the definite aetiology and aetiopathogenetic mechanisms that underlie AIS are still unclear. Thus, at present, both the prevention of AIS and the treatment of its direct underlying cause are not possible.

To our knowledge there are no publications that have evaluated physical activities in relation to the etiopathogenesis of adolescent idiopathic scoliosis (AIS) other than sports scolioses. In a preliminary longitudinal case-control study, mother and child were questioned and the children examined by one observer. The aim of the study was to examine possible risk factors for AIS. Two study groups were assessed for physical activities: 79 children diagnosed as having progressive AIS at one spinal deformity centre (66 girls, 13 boys) and a Control Group of 77 school children (66 girls, 11 boys), the selection involving six criteria. A structured history of physical activities was obtained, every child allocated to a socioeconomic group and examined for toe touching. Unlike the Patients, the Controls were not X-rayed and were examined for surface vertical spinous process asymmetry (VSPA). Statistical analyses showed progressive AIS to be positively associated with social deprivation, early introduction to indoor heated swimming pools and ability to toe touch. AIS is negatively associated with participation in dance, skating, gymnastics or karate and football or hockey classes, which might suggest preventive possibilities. There is a significantly increased independent odds of AIS in children who went to an indoor heated swimming pool within the first year of life (odds ratio 3.88, 95% CI 1.77-8.48; p = 0·001). Furthermore fourteen (61%) Controls with VSPA compared with 9 (17%) Controls without VSPA had been introduced to the swimming pool within their first year of life (P < 0.001). Early exposure to indoor heated swimming pools for both AIS and VSPA, suggests that the AIS findings do not result from sample selection.

This paper aims to integrate into current understanding of AIS causation, etiopathogenetic information presented at two Meetings during 2012 namely, the International Research Society of Spinal Deformities (IRSSD) and the Scoliosis Research Society (SRS). The ultimate hope is to prevent the occurrence or progression of the spinal deformity of AIS with non-invasive treatment, possibly medical. This might be attained by personalised polymechanistic preventive therapy targeting the appropriate etiology and/or etiopathogenetic pathways, to avoid fusion and maintain spinal mobility. Although considerable progress had been made in the past two decades in understanding the etiopathogenesis of adolescent idiopathic scoliosis (AIS), it still lacks an agreed theory of etiopathogenesis. One problem may be that AIS results not from one cause, but several that interact with various genetic predisposing factors. There is a view there are two other pathogenic processes for idiopathic scoliosis namely, initiating (or inducing), and those that cause curve progression. Twin studies and observations of family aggregation have revealed significant genetic contributions to idiopathic scoliosis, that place AIS among other common disease or complex traits with a high heritability interpreted by the genetic variant hypothesis of disease. We summarize etiopathogenetic knowledge of AIS as theories of pathogenesis including recent multiple concepts, and blood tests for AIS based on predictive biomarkers and genetic variants that signify disease risk. There is increasing evidence for the possibility of an underlying neurological disorder for AIS, research which holds promise. Like brain research, most AIS workers focus on their own corner and there is a need for greater integration of research effort. Epigenetics, a relatively recent field, evaluates factors concerned with gene expression in relation to environment, disease, normal development and aging, with a complex regulation across the genome during the first decade of life. Research on the role of environmental factors, epigenetics and chronic non-communicable diseases (NCDs) including adiposity, after a slow start, has exploded in the last decade. Not so for AIS research and the environment where, except for monozygotic twin studies, there are only sporadic reports to suggest that environmental factors are at work in etiology. Here, we examine epigenetic concepts as they may relate to human development, normal life history phases and AIS pathogenesis. Although AIS is not regarded as an NCD, like them, it is associated with whole organism metabolic phenomena, including lower body mass index, lower circulating leptin levels and other systemic disorders. Some epigenetic research applied to Silver-Russell syndrome and adiposity is examined, from which suggestions are made for consideration of AIS epigenetic research, cross-sectional and longitudinal. The word scoliogeny is suggested to include etiology, pathogenesis and pathomechanism.

Adolescent idiopathic scoliosis (AIS) is a 3-D spinal deformity with uncertain etiology; abnormalities in brain development represent one of the possible explanatory concepts for its pathogenesis. The objective of this study is to investigate the brain maturation by thickness of cerebral cortex among female adolescents with and without idiopathic scoliosis. Fifty AIS patients with a typical right-thoracic curve pattern were compared with 40 age-matched healthy controls. Based on the T1-weighted magnetic resonance images, the thickness of cortical gray-matter was calculated using a well-validated surface measurement method. Focusing on adolescent participants within the age range with the frequent occurrences of AIS cases (i.e., 12 to 17 years), we observed that the cortical thickness declined significantly in almost all cortical lobes in normal subjects (Spearman correlation<-0.4; P ≤ 0.05) except temporal lobe in LH, while in AIS patients this decline was weakly correlated with age (Spearman correlation>-0.4) and largely insignificant (P ≥ 0.05). Quadratic regression results expressed the detailed difference in the age-related cortical changing pattern between the two groups. In addition, focal cortical thickness was significantly different in AIS patients compared with healthy controls in areas involved in motor and vestibular functions as well as object recognition. The findings from this study imply a different thinning pattern of the cerebral cortex during adolescence in patients with AIS; this may be primary (i.e. etiopathogenetic) or secondary (i.e. adaptation) to the development of scoliosis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Although considerable progress had been made in the past two decades in understanding the etiopathogenesis of adolescent idiopathic scoliosis (AIS), it still lacks an agreed theory of etiopathogenesis. One problem may be that AIS results not from one cause, but several that interact with various genetic predisposing factors. There is a view there are two other pathogenic processes for idiopathic scoliosis namely, initiating (or inducing), and those that cause curve progression. Twin studies and observations of family aggregation have revealed significant genetic contributions to idiopathic scoliosis, that place AIS among other common disease or complex traits with a high heritability interpreted by the genetic variant hypothesis of disease. We summarize etiopathogenetic knowledge of AIS as theories of pathogenesis including recent multiple concepts, and blood tests for AIS based on predictive biomarkers and genetic variants that signify disease risk. There is increasing evidence for the possibility of an underlying neurological disorder for AIS, research which holds promise. Like brain research, most AIS workers focus on their own corner and there is a need for greater integration of research effort. Epigenetics, a relatively recent field, evaluates factors concerned with gene expression in relation to environment, disease, normal development and aging, with a complex regulation across the genome during the first decade of life. Research on the role of environmental factors, epigenetics and chronic non-communicable diseases (NCDs) including adiposity, after a slow start, has exploded in the last decade. Not so for AIS research and the environment where, except for monozygotic twin studies, there are only sporadic reports to suggest that environmental factors are at work in etiology. Here, we examine epigenetic concepts as they may relate to human development, normal life history phases and AIS pathogenesis. Although AIS is not regarded as an NCD, like them, it is associated with whole organism metabolic phenomena, including lower body mass index, lower circulating leptin levels and other systemic disorders. Some epigenetic research applied to Silver-Russell syndrome and adiposity is examined, from which suggestions are made for consideration of AIS epigenetic research, cross-sectional and longitudinal. The word scoliogeny is suggested to include etiology, pathogenesis and pathomechanism.

Introduction: Trunkal back asymmetry is considered very important for the selection of children at risk of developing scoliosis. Traditionally, this asymmetry as thoracic or lumbar hump is the main indicator for referral of subjects with idiopathic scoliosis (IS) to clinics from school-screening programs. This asymmetry is also used as the most important sign for further assessment at scoliosis clinics. There are reports suggesting that an epigenetic risk factor for IS is maternal age at birth. However, the influence of maternal age on the development of trunkal asymmetry during growth has not been reported. This report aims to assess if maternal age at birth impacts trunkal asymmetry, and how this parameter may dictate the epigenotypic expression of the trunkal asymmetry of a child., Material and Methods: The sample examined: 11832 (5855 males and 5977 females) children and adolescents (5-17 years old, mean age: 11.34±2.79) were screened at their school for back trunkal asymmetry and/or scoliosis. The measurements: The Prujis scoliometer was used to examine the students in standing and sitting forward bending positions. If at least one of child's measured angles was equal to or exceeded 6 or 7 degrees of scoliometer reading, it was labelled as "Asymmetry-6" and "Asymmetry-7" respectively. The age, standing height and body weight of children and maternal age were also documented, among other parameters. The maternal age at birth and children's BMI were subsequently calculated. The statistical analysis: Asymmetries were tested for correlation with maternal age at birth which was transformed to a categorical variable using 5-year intervals. Pearson's χ2 test was used for the univariate analysis, while logistic regression was used for quantitative univariate and multivariate analysis. Statistical significance level was set to p<.05. SPSS and STATA TM v. 11.0 statistical packages were used for the analysis., Results: Univariate analysis: Univariate analysis showed that the prevalence of asymmetry-6 in boys tended to significantly decrease as mother's age at birth increased (mother's age at birth: <19, 20-24, 25-29, 30-34, 35-39, >40 years, % of asymmetry-6: 11.5%, 9.5%, 8.5%, 7.6%, 5.2%, 5.3%, respectively, (p=0.026). This trend, although present, was not significant in girls. The prevalence of asymmetry-7 also showed a decreasing trend, which was only significant in boys (mother's age at birth: <19, 20-24, 25-29, 30-34, 35-39, >40 years, % of asymmetry-7: 8.7%, 5.9%, 5.9%, 4.6%, 2.6%, 3.5%, respectively, p=0.010). Maternal age at birth, as a continuous variable, was inversely associated with the appearance of asymmetry-6 in both boys and girl s (OR: 0.966, 0.982, 95%CIs: 0.947-0.985, 0.965-0.999, p: 0.001, 0.040, respectively). This was also the case for asymmetry-7 only in boys: (OR: 0.961, 0.982, 95%CIs: 0.938-0.985, 0.962-1.003, p: 0.001, 0.088, respectively). Multivariate analysis: The significant and inverse effect of maternal age at birth on the appearance of asymmetry in boys remained even after adjusting for child's BMI and age. For one year increase of maternal age at birth, the odds of the boys being asymmetrical6 were reduced by 2.8% (OR:0.972, 95% CIs: 0.953-0.992, p: 0.005), adjusting for child's age and BMI. For one year increase of maternal age at birth, the odds of the boys being asymmetrical7 were reduced by 3.2% (OR:0.968, 95% CIs: 0.945-0.992, p: 0.010), adjusting for child's age and BMI. However, the aforementioned correlations were not significant for girls in both cases., Discussion and Conclusions: The influence of maternal age at birth on the development of trunkal asymmetry during growth has not been previously assessed, as evidenced from literature review. The findings of this report indicate that maternal age as an environmental factor in the general population, may possibly influence epigenetically, the occurrence of the initial presentation of trunkal asymmetry in males more than females, as well as IS during growth. Consistent findings reported from the USA, Edinburgh and Sweden reveal increased maternal age as a risk factor for AIS, suggesting maternal factors can predispose to it. It seems that males are more affected by this factor but, unexpectedly in this study, by younger and not older mothers, as reported for AIS in the literature. Low-birth weight associated with younger parental age may also be associated with increased trunkal asymmetry particularly of boys, an hypothesis that need testing. The importance our findings is based on the belief that the intra-uterine environment is crucial in programming the fetus for various health and disease outcomes throughout life.