Background: To our knowledge, there are no publications that have evaluated physical activities in relation to the etiology of AIS other than sport scoliosis (1,2) so we undertook a study to assess the physical activities of patients with progressive AIS from their first year to early teens and compared these with those of a control group.

Methods: All 156 children in this study had to adhere to the following 6 criteria:- born full term, fed well as infants, achieved their milestones, no hospital visits except for sports injuries, no family history of a scoliosis and no back pain (prior to diagnosis in the patient group). We compared 79 consecutive patients (girls 66, boys 13) diagnosed as progressive AIS (62 of whom subsequently had a spinal fusion) with a control group of 77 subjects (girls 66, boys 11) of similar age, gender, race and socioeconomic status. A structured history was obtained from the mother and child of each group average time taken to obtain the history was 47 minutes. Each child was examined for toe touching and vertical symmetry of spinous processes whilst standing. The findings suggest a relation between physical activities or the lack of them and the development of progressive AIS.

Results: There is a significantly increased odds of AIS in those who were introduced to a swimming pool within the first year of life (p=0.001), did not attend gymnastics/ karate classes (p=0.005), did not attend dance classes (girls only, p=0.045), did not have horse riding classes (p=0.003), did not go skating (< 0.001), and who could touch their toes (p=0.011). No association is found with playing football/hockey or regular swimming at the age of 10 years.

Conclusion: Progressive AIS is positively associated with an early introduction to swimming and ability to toe touch. Spinal asymmetry was noted in the controls. AIS is negatively associated with participation in dance, skating, gymnastics/karate and horse riding classes. Is it possible that children who develop AIS have a longstanding proprioception defect which makes them less likely to participate in sporting activities? If so, by encouraging children to participate in sport might we increase their proprioception abilities and make those at risk less likely to develop spinal asymmetry which may progress to a scoliosis requiring surgical correction?

Objective. Despite the current revolution in molecular medicine that has benefitted the treatment of certain diseases (Ross 2002), idiopathic scoliosis has resisted attempts to understand the molecular basis of its curve development. Lowe et al (2002) in a longitudinal study of 55 AIS patients concluded that platelet calmodulin levels correlate closely with curve progression and stabilization by bracing or spine fusion. They suggest that the platelet is a “minimuscle” with a protein contractile system (actin and myosin) similar to that of skeletal muscle. Using Lowe’s data we found that percentage platelet calmodulin change correlates significantly with percentage Cobb angle change (ANOVA, p=0.0003, n=54) that led us to suggest a platelet/skeletal hypothesis to account for their findings as part of a cascade concept for the pathogenesis of AIS.

Hypothesis. The human immature vertebral body is unusual among mammals in lacking epiphyses. This may explain why an axial load transmitted directly from the intervertebral disc deforms mature vertebral body end-plates as an axial inward bulge (Brinckmann et al 1983). In immature normal vertebral bodies vascular “lakes” (resembling bunches of grapes) have been found adjacent to the disc growth plates in subjects aged 9 to 13 years of age (Mineiro 1965). These “lakes” may provide a susceptibility to platelet activation from vascular stasis and shear stresses. In addition to their role in hemostasis platelets contain many growth factors including TGF-βs in α-granules that are secreted at a fracture site (Bolander 1992). TGF-βs are found in human neonatal rib growth plates (Horner et al 1998) but, like estrogen receptors, have not yet been sought in human intervertebral disc growth plates. We hypothesize that in the presence of a small scoliosis curve (from unknown causes ?spine, rib, muscle, or nervous system) platelets, as they circulate through vessels in eccentrically-loaded and deforming immature vertebral bodies particularly about the curve apex in the presence of a basic defect, are activated also by repeated axial inward bulges of disc growth plates causing mechanical micro-insults with endothelial cell desquamation and the formation of a calcium-cadmodulin complex. The latter is associated with platelet contraction (shape change) and the secretion from α-granules of various growth factors including angiogenic regulators (platelet release reaction, Hartwig 2003, Reed 2002, Rendu and Brohard-Bohn 2002). These growth factors abet the hormone-driven growth of the already mechanically-compromised disc growth plates and induce anterior spinal overgrowth and curve progression. The basic defect in AIS could be 1) a platelet, endothelial, or subendothelial anomaly, defect, or functional (?hormonal) disorder, and 2) one or more genetic polymorphisms that involve platelet receptors (Afshar-Kharghan and Bray 2002) and putative estrogen receptors in vertebral disc growth plates (Inoue et al 2002ab). The predilection of progressive AIS for girls may be related to the cyclical platelet functions in women associated with normal uterine function (Jones et al 1983, Pansini et al 1986, Tarantino et al 1994, Faraday et 1997). Curve laterality is determined by factors that initiate curve progression. Low plasma melatonin of progressive AIS may act both by a reduced antagonism to calmodulin (Lowe 2000, Dubousset and Machida 2001) and facilitating platelet aggregation with secretion of growth factors from α-granules.

Conclusions. The platelet/skeletal hypothesis for progressive AIS and the cascade concept suggests much new research. The hypothesis has genetic, diagnostic, prognostic and potential therapeutic implications. It raises questions about the possibility of changes in platelet calmodulin levels in other progressive and resolving deformities that occur in the immature and adult skeleton.

Objective. To evaluate the relation of ribs to the spine in the transverse plane (TP) at the curve apex in preoperative AIS using a real-time ultrasound method and radiographs (Burwell et al 2002).

Design. With the subject in a prone position and head supported, readings of laminal rotation (LR) and rib rotation (RR) were made on the back by one of two observers (RKA, ASK) using an Aloka SSD 500 portable u/s machine with a veterinary long (172mm) 3.5 MHz linear array transducer. The maximal difference between LR and RR about the curve apex was calculated as the apical spine-minus-rib rotation difference (SRRD). The SRRD eliminates the effect of any anterior chest wall asymmetry on the ultrasound measurements and, assuming no movement of ribs in the TP at the costotransverse joints, is considered to be a measure of TP rib deformity. The radiographic Cobb angle (CA), apical Perdriolle rotation (AR), and apical vertebral translation (AVT) were measured by one observer (RGB). In an attempt to separate mechanical axial vertebral rotation from axial vertebral deformity a derivative was calculated as Perdriolle rotation minus ultrasound LR with the latter corrected for the positional effect of lying prone and termed the axial vertebral difference (AVD) The correction factor (CF) used is maximal Scoliometer angle of trunk rotation obtained in the standing forward bending position minus that in the prone position.

Subjects. Thirty-three preoperative patients with AIS were studied (thoracic curves 20, thoracolumbar curves 8, double curves 5).

Results. The mean figures in degrees or mm (AVT) are shown in the Table.

All curves combined. The LR is significantly greater than the RR (p< 0.001) and correlates with RR (r=0.358, p=0.041), SRRD (r=0.713, P< 0.001) but not with CA (p=0.088), AR (p=0.166), AVT or AVD. AR does not correlate significantly with CA.

Thoracolumbar and thoracic curves. In the thoracolumbar curves the SRRDs are significantly greater than those in the thoracic curves (p=0.031) implying more TP rib deformity in the thoracolumbar curves. In the thoracic curves the SRRDs correlate negatively with the AVDs (r= −0.470, p=0.036) suggesting that rib deformity and intravertebral deformity contribute reciprocally and together with axial spinal rotation to determine the overall spinal deformity of AIS.

Conclusions. The findings are consistent with the hypothesis that in preoperative AIS the axial RR and TP rib deformities are adaptations to rotational and lateral forces imposed by the scoliotic spine (Wever et al 1999). Might surgical stiffening of the posterior ends of the apical convex ribs – in an attempt to prevent TP convex rib deformity – constrain axial spinal rotation, vertebral translation and intravertebral deformity and limit curve progression? #Supported by AO/ASIF Research Commission Project 96-W21

Nachemson (1996), drawing upon the theses of Sahlstrand (1977) and Lidström (1988), articulated the view there are more girls than boys with progressive AIS for the following reason. The maturation of postural mechanisms in the nervous system is complete about the same time in boys and girls. Girls enter their skeletal adolescent growth spurt with immature postural mechanisms – so that if they have a predisposition to develop a scoliosis curve, the spine deforms. In contrast boys enter their adolescent growth spurt with mature postural mechanisms so that they are protected from developing a scoliosis curve. There is evidence that postural sway improves with age in boys and girls until about 10 years of age after which it is similar between the sexes (Hirashawa 1973, Odenrick and Sandstedt 1984) findings which need further evaluation. We term Nachemson’s concept the neuro-ossesous timing of maturation (NOTOM) hypothesis. It may have an evolutionary basis through natural selection towards sexual and skeletal development during adolescence being earlier in girls and later in boys.

The NOTOM hypothesis suggests a treatment to prevent progression of late-juvenile idiopathic scoliosis, early-AIS, and some secondary scolioses based on delaying the onset of puberty used therapeutically in girls with idiopathic precocious puberty (IPP, Grumbach and Styne 1998). The proposal is to administer a gonadorelin analogue which in the pituitary down-regulates the receptors to hypothalamic gonadotropin-releasing hormone (GnRH) causing a fall in both luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which in turn causes a fall in oestrogens and androgens, and thereby delays or stops menarche and slows bone growth – as in girls and boys with IPP (Galluzzi et al 1998). Expert scrutiny of this therapeutic proposal is currently in progress.