Aetiology of Idiopathic Scoliosis. Current Concepts , Burwell

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PEDIATRIC REHABILITATION, 2003, VOL. 6, NO. 34, 137170

Aetiology of idiopathic scoliosis:current concepts

R. G. BURWELL

Accepted for publication: October 2003

Keywords Scoliosis, aetiology, puberty, spine, thorax,asymmetry

Summary

The aetiology of the three-dimensional spinal deformity ofidiopathic scoliosis (IS) is unknown. Progressive adolescent

idiopathic scoliosis (AIS) that mainly affects girls is generallyattributed to relative anterior spinal overgrowth from amechanical mechanism (torsion) during the adolescent growthspurt. Established biological risk factors to AIS are growthvelocity and potential residual spinal growth assessed bymaturity indicators. Spine slenderness and ectomorphy ingirls are thought to be risk factors for AIS. Claimedbiomechanical susceptibilities are (1) a fixed lordotic areaand hypokyphosis and (2) concave periapical rib overgrowth.MRI has revealed neuroanatomical abnormalities in 20%of younger children with IS. A neuromuscular cause for AISis probable but not established. Possible susceptibilities toAIS in tissues relate to muscles, ligaments, discs, skeletal pro-portions and asymmetries, the latter also affecting soft tissues(e.g. dermatoglyphics). AIS is generally considered to be

multi-factorial in origin. The many anomalies detected, partic-ularly leftright asymmetries, have led to spatiotemporalaetiologic concepts involving chronomics and the genomealtered by nurture without the necessity for a disease process.Genetic susceptibilities defined in twins are being evaluatedin family studies; polymorphisms in the oestrogen receptorgene are associated with curve severity. A neurodevelopmentalconcept is outlined for the aetiology of progressive AIS. Thisconcept involves lipid peroxidation and, if substantiated, hasinitial therapeutic potential by dietary anti-oxidants. Growthsaltations have not been evaluated in IS.

Introduction

The question of aetiology must be answered if logicalpreventive and therapeutic measures are to be devised [1].

terminology

The word aetiology strictly means the factor(s) caus-

ing the condition, pathogenesis its mode of origin and

pathomechanismthe sequence of events in the evolution

of its structural and functional changes [2]. Although

the discussion here relates more to pathogenesis and

pathomechanisms than to the aetiology of AIS, the

term aetiology, or aetiopathogenesis, is used to embraceall aspects of causation. Attention is directed mainly

to progressive AIS with a few comments on juvenile

idiopathic scoliosis (JIS) and infantile idiopathic scolio-

sis (IIS). Pelvic tilt scoliosis is not considered.

Torsion has two meanings [3]: (1) a local geometric

property of the vertebral body (geometric torsion or

tortuosity) and (2) axial plane angulations between speci-

fied vertebrae (mechanical torsion, or axial rotation).

historical

During the 19th

century, three main concepts ofcausation of IS emerged, namely (1) myopathic

(Gue rin), (2) malpostural (Lovett) and (3) osteopathic

(Schulthess); the latter holding that rickets or endocrine

factors were important in causation [4, 5].

difficulties in deciphering the aetiology of

AIScurrent research and the need for

concepts

Once a scoliotic curve is established, attempts to

determine the biological and biomechanical mecha-

nisms [6] that led to its formation are difficult to deci-

pher [7] and have been likened to the reconstruction of

a railroad accident (Lovett) and to archaeology [8].

However, as Urban [9] pointed out, as scoliosis occurs

during the growth spurt, it is likely that the growth

plate is a major factor in the development of a scoliotic

deformity.

Current aetiologic research on AIS is focusing on

biological and biomechanical factors. The research is

Pediatric Rehabilitation ISSN 13638491 print/ISSN 14645270 online # 2003 Taylor & Francis Ltdhttp://www.tandf.co.uk/journals

DOI: 10.1080/13638490310001642757

Author: R. G. Burwell, MD FRCS, Emeritus Professor,University of Nottingham, UK; Honorary Consultant, TheCentre for Spinal Studies and Surgery, University Hospital,Nottingham, UK. email: [email protected]


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multi-disciplinary and relates mainly to growth, the cen-

tral nervous system (CNS), melatonin, muscles, platelet

calmodulin, bone density, elastic fibres, the skeletal

framework including vertebral disproportionate growth

and genetics [6, 1018]. Growth saltations and stasis

during puberty [19] have not been evaluated in AISsubjects.

There is no generally accepted theory for the aetiol-

ogy of AIS [13, 14]. Many concepts have arisen in the

struggle to understand the causation of AIS, but they

have not been published collectively. Their aim is to

clarify thought and help to plan new researches with

the ultimate aim of improving prognosis and attaining

prevention.

an overall concept for the aetiology of AIS

Emerging as an overall concept for the aetiology of

progressive AIS in girls is the timing of the adolescent

growth spurt in relation to maturational changes that

occur during puberty in the spine, thorax and nervous

system. This concept is in accordance with current

knowledge that:

1. Growth is more than an increase in size and

includes the maturation of the child [20, 21]. A

recent paper [18] has shown that AIS girls have

anomalous vertebral proportions involving dis-

proportionate endochondral-membranous growth

and spine slenderness. Subject to confirmation, thefindings suggest new concepts of aetiology and

prognosis for progressive AIS and with it the

potential for selective early preventive surgery.

2. In embryogenesis spatio-temporal control involves

internal clocks, the temporal aspects of which are

termed chronomics [22, 23].

Knowledge from developmental biology has been used

to create three multi-factorial spatio-temporal concepts

for the aetiology of AIS, but none is fully integrated

with existing knowledge about the causation of AIS.

a neurodevelopmental concept as part of an

holistic concept of aetiology

A neurodevelopmental concept is outlined for the

aetiology of progressive AIS in girls. The concept

involving lipid peroxidation, if substantiated, has initial

therapeutic potential by dietary anti-oxidants.

Spinal concepts

the scoliotic spine as an helixtorsions and

counter-torsions

Perdriolle and Vidal [24] proposed that the scoliotic

spine, when observed from above, progresses with theapical vertebrae moving in an arc, anterior to posterior,

around the upper end vertebra; this explained the three

successive stages of lordosis, flat back and paradoxical

kyphosis when viewed from the side. Asher and Burton

[25] confirmed this view and maintained that thoracic,

thoracolumbar and lumbar scoliosis deformities evolve

as imperfect torsions and counter-torsions similar to an

elongated helical line and not as mechanical torsions

in which two objects immediately adjacent are rotated

on each other.

the scoliotic spine as a columntheory and

buckling

Column theory and biology

Millner and Dickson [6] stated that the deformity of

IS is three-dimensional, resulting from viscoelastic

buckling of the spine in both the coronal plane (pro-

ducing a lateral bend) and the transverse plane (axial

rotation or torsional buckling) as a lordoscoliosis in

an approximation of Eulers Laws. For a progressive

deformity to ensue, the buckling process must occur

during spinal growth. Biological factors bring the spinal

column to and beyond its buckling threshold so that

a taller and slender spine is more liable to bend and,

being stiffer in the sagittal plane, favours movementin other planes. The opposite they stated occurs in

Scheuermanns disease, where the deformity is rotation-

ally stable and remains in the sagittal plane.

spine and vertebral slendernessgender

difference link ed to curve progression and

expressed in th e body build of AIS subjects?

In the technical theory of column buckling, slender-

ness is defined as the ratio of the square of the columns

length to the moment of inertia of its cross-sectional

area [26]. Spine slenderness has been suggested as one

factor in the predisposition of girls spines to buckle

under load and develop progressive AIS [6, 26, 27].

Normal vertebraegenetic and epigenetic

factorsdifferential growth and spinal deformity

In normal spines, sexual dimorphism in vertebral

body shape has been found, with female vertebral bodies

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R. G. Burwell


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being more slender than male vertebral bodies from 8

years onwards [28], as well as in spine slenderness

where spinal length is taken into the equation [26].

Sexual dimorphism implies a genetic control in the

relative contribution of endochondral ossification and

periosteal bone formation to vertebral body shape [29].According to Ganey and Ogden [30], vertebral growth

not only relies on genetic factors but also responds

to epigenetic factors including paravertebral muscle

tone, upright posture, physical activity, intermittent

hydrostatic compression emanating from the discs

and the check-rein effect of the periosteum [27, 30].

While vertebral body height in the mid-sagittal plane

may be primarily genetically determined and relatively

unaffected by mechanical factors, peripheral vertebral

growth (anteroposterior and latitudinal) is more

dependent on the upright posture [30, 31]. The concept

has been suggested [30] that the differential growth

response of the peripheral (membranous as well asendochondral ossification) vs central portions (endo-

chondral ossification) may be a factor in the eccentric

growth patterns that lead to the development and

progression of scoliosis and kyphosis.

Idiopathic scolotic vertebraegender difference

confirmed

In the thoracolumbar spine of children with IS,

Skoglund and Miller [32] reported higher vertebral

height/width indices, suggesting an increased slender-

ness compared with non-scoliotic children. This findingwas questioned by Veldhuizen et al. [33], but they

confirmed a gender difference in vertebrae from AIS

subjects. The latter finding supports a role for spinal

slenderness in progressive AIS curves [18] where females

predominate and less so in curve initiation(or induction)

where the female-to-male prevalence is similar.

The external phenotype of AIS subjects

Spine slenderness may reflect the somatotype of AIS

girls who are more ectomorphic and less mesomorphic

than healthy girls; and ectomorphy may be associated

with a susceptibility to curve progression [3436].

These concepts need testing, including an evaluation

of the relation of vertebral and spine slenderness to

disproportionate (uncoupled) anterior/posterior verte-

bral growth [18]. The body composition profile in AIS

girls (weight, body mass index, percentage of body fat

and somatotype) was found to be anomalous [37].

Possible implications of a more ectomorphic

phenotype

Coillard and Rivard [38] suggested that being ecto-

morphic means mesodermal derivatives are in some

respects underdeveloped, with their skeleton and

muscles being longer and frailer than they are strongor stocky. In the event of disturbance, the neuromuscu-

loskeletal stability is diminished, making greater the

risk of deterioration.

relative lengthening of the anterior spinal

columndisproportionate endochondral-

membranous bone growthdo these findings

represent vertebral slenderness linked to

ectomorphy? concepts for AIS aetiology and

prognosis

Relative lengthening of the anterior spinal column

The long-held view [27, 39] that scoliosis is an isolated

growth lengthening of the anterior spinal column with

torsion has been confirmed by more recent anatomical

studies of structural scoliosis [18, 4044]. This relative

anterior spinal overgrowth, the result of vertebral body

growth plate activity, is generally considered to explain

the apical vertebral translation and both the geometric

and mechanical torsion of the scoliotic spine. Roaf [40]

pointed out that while it is possible to have a lordosis

without rotation and lateral curvature, the sternum and

abdominal muscles prevent this.

Disproportionate endochondral-membranous bone

growthaetiologic and prognostic?

In a recent whole spine MRI study of 83 girls with

AIS and 22 age-matched controls, Guo et al. [18] found

longer vertebral bodies between T1 and T12in the ante-

rior column and shorter pedicle heights with longer

inter-pedicular distances in the posterior column.

Scoliosis curve severity correlated significantly with

the ratio of vertebral body length to pedicle height at

all thoracic levels. It was concluded that uncoupled

endochondral-membranous bone formation causes the

relative anterior spinal overgrowth in AIS that may

allow the potential for progression of the deformity.

The mechanism is considered to be an intrinsic

abnormality of skeletal growth that may be genetic.

Importantly, the morphological vertebral patterns

may be prognostic for curve progression in AIS

girls [18] and with it the potential for selective early

preventive surgery.

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An additional hypothesisvertebral slenderness

predisposes to curve progression in AIS

There is an additional hypothesis to explain their

findings; namely that spine slenderness predisposes

to AIS progression involving both membranous and

endochondral ossification [30]. The vertebral featuresdescribed by Guoet al. [18] may be those of individuals

more ectomorphic than the controls. More research

is needed, including vertebral shape in relation to

somatotyping in scoliotic and normal subjects.

Concepts for AIS aetiology

Three concepts or schools of thought that may

account for the relative anterior spinal overgrowth

(RASO) in AIS girls are:

1. Primary morphological feature [18]. The RASO

results from an intrinsic abnormality of skeletal

growth involving vertebral disproportionate verte-

bral body height (significant sequentially from T612)

that may be genetic. An additional morphological

feature was vertebral body anteroposterior and

latitudinal size (recorded only at T6) that was not

significantly different from the controls implying

vertebral body slenderness of width relative to

height.

2. Secondary morphological feature [44]. Before the

publication of the paper of Gou et al. [18], the

RASO was thought to be localized to the scoliosis

curve and result from extrinsic mechanical factorsincluding gravity, tonic muscle action [45, 46], a

short spinal cord [44, 47] or failure of growth of

the posterior elements of a segment of the spine

[48]. This concept does not explain the finding

that scoliosis curve severity correlated significantly

with the ratio of vertebral body height to pedicle

height at all thoracic levels [18]. A third concept is

needed.

3. Third and holistic concept. The findings of Guoet al.

[18] can be used to show that the RASO is maxi-

mum at T9 and T10 (respective increase of 12% and

10% relative to the controls against an average of

6% increase from T112). This suggests that aboutthe curve apex there are superimposed biomechanical

and biological features to cause the increased peri-

apical RASO (with or without other planes being

involved). Theoretical requirements for this concept

to explain progressive AIS include:

(a) Putative primary ligamentous or neuromuscular

mechanisms acting directly on the spine and

possibly indirectly through the ribcage in

susceptible girls withprimary vertebral morpho-

logical features [19] including hypokyphosis

to initiate a 3D thoracic scoliotic deformity

with a short segment lordosis.

(b) The scoliotic deformity may then provoke asecondaryapical RASO as part of an increasing

3D deformity through growth-induced torsion

during the adolescent growth spurt that is

enabled and potentiated by obligatoryhormonal

activity and possibly platelet activation,

perhaps in relation to postural maturation.

Other factors that may contribute to curve

progression include less torsional rigidity of

younger intervertebral discs,more mobile spines,

a growth force when some vertebral bodies

and discs outgrow their surrounding tissues

and a large extrathoracic skeleton relative to

chest size in a putative mechanism affectingspinal biomechanics in gait and other activities.

neurocentral synchondroses (NCSs)pedicle

length asymmetry at 6 years

The relationship of NCSs to the aetiology of IS is

unknown. The concept that greater growth of the apical

concave NCS is aetiologic for AIS is controversial

because of lack of agreement on the exact age at

which closure occurs [30, 4951]. The pedicle length

asymmetries of mid-thoracic vertebrae generallyobserved by 6 years of age [52] were confirmed by

Taylor [53], who suggested that longer left pedicles

about 8 years by rotating the vertebral body to the

right may predispose a girl to the development of IS

at a later age. Farkas [52] interprets the pedicle asym-

metry as one of torsion and a delusion of rotation.

facet joints?growth a symmetry and

loop effect

According to Roaf [42], the earliest morphological

changes of slight scoliosis are hypoplasia and alteration

of the alignment of the articular processes on the con-

cave side. Later, these changes become very marked

with degeneration, osteophytes and bony ankylosis [27].

Ganey and Ogden [30] suggest the concept that

alteration of rates of growth can affect the shape of

posterior elements and secondarily affect muscle func-

tion, which affects growth rates (loop effect).

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osteopeniagender difference in healthan

AIS sub-group having low skeletal mass, or

are the vertebral findings due to spine

slenderness?

Bone mass accumulation in healthBone mass accumulation in the spine during puberty

in girls is restricted to a 4-year period at 1115 years of

age. In boys, the acceleration in bone mass accumula-

tion is delayed to that of girls and is particularly

pronounced from 1317 years [54] to reach a plateau

in the third decade of life. Peak bone mass is strongly

affected by genetic (7580%), nutritional (such as

calcium, vitamin D and dietary fats [55]), lifestyle

and environmental factors as well as hormones, espe-

cially oestrogen [56, 57]. Dietary calcium in girls during

puberty is believed by some to be below recommended

levels [58].

AIS

Cheng [18, 56] concluded that there is a clear associ-

ation between AIS and generalized osteopenia and

opined that intra-skeletal mechanisms can contribute

to the pathogenesis of AIS. In contrast, Lowe et al.

[14] concluded that they were not aware of any evidence

that inferior bone quality was an important factor in

the aetiology of IS. Courtois et al. [59] found lower

bone mineral densities in the patients than the controls

in 33 young women with AIS and brace treated

and suggested a need for osteopenia screening and pre-vention in children with scoliosis. Most recently,

Guo et al. [18] suggested that the low bone mineral

density in AIS subjects previously reported by Cheng

[56] could represent a relatively small bone mass and

slower circumferential bone growth.

Previous to the paper of Guo et al. [18], Cheng [56]

suggested multi-centre studies on the prevalence of low

bone mineral density among AIS patients, including

anthropometric data, skeletal growth pattern, associ-

ated life style risk factors of osteopenia, biochemical

bone turnover profile and genetic studies. The therapeu-

tic hope was that treatment to improve bone mineral

status would alter the natural history of the scoliotic

deformity. In this connection, a synthesized estrogen-

like hormone, estren, may become the first of a new

class of osteoporosis drugs termedANGELS(activators

of nongenomic estrogen-like signalling) [60]. In the light

of the findings of Guo et al. [18], bone mineral density

studies should include evaluation of vertebral morphol-

ogy and somatotyping.

Goto et al. [61], in a finite element study, implicated

bone resorption in the aetiology of AIS.

inter-vertebral discs (IVDs)not a prim ary

factor but discs contribute to th e deform ity

While the inter-vertebral disc does not appear to be

the primary factor in the aetiology of IS, as it becomes

significantly and irreversibly wedged [62] the disc

contributes to the development of the scoliosis curve

[63, 64]. Roberts et al. [65] concluded that it is very

likely that the changes in cartilage endplate (vertebral

body growth plate) and IVDs are key factors in the

progression of scoliosis and the manner in which the

curve will respond to different therapeutic regimens.

According to Taylor and Melrose [66], the response of

IVDs to abnormal stresses imposed on them in scolio-

sis is central to the long-term prognosis of untreated

lumbar and thoracolumbar curves.The diurnal variation in the water content of lumbar

IVDs evident on MRI in two young adult subjects [67]

was suggested as a contributory factor to the scoliosis

deformity. Aulisaet al. [68] concluded that the torsional

rigidity of the inter-vertebral discs increased throughout

growth that favoured the progression of early scoliotic

curves.

spinal mobility in h ealthy and scoliotic

childrendo girls have stiffer spines and

if so most in which plane?

Dickson and Weinstein [69] stated that girls havestiffer spines than boys and that is one of the mechan-

ical reasons favouring buckling of the vertebral column.

Spinal flexibility during deep inspiration

Lowden et al. [70] examined 442 healthy children

aged 815 years using a Kyphometer and confirmed

that girls but not boys kyphosis reduced to a minimum

at 11 years of age. They showed that sagittal spinal

flexibility during a deep inspiration showed striking

changes with age: it increased at 11 years of age signifi-

cantly more so in boys and decreased significantly from

1215 years of age, suggesting thoracic spinal stiffening.

Lumbar spinal flexibility increased significantly in girls

but not boys at 10 years of age.

Spinal mobility in healthy children

Mellin and Poussa [71] examined 294 healthy children

aged 816 years in five age groups and found that each

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of thoracic extension, lateral flexion and rotation

decreased significantly from 1213 years in boys and

girls. In the thoracic spine at 13 years of age girls,

compared with boys, had less kyphosis and were stiffer

in forward and lateral flexion, with more rotation to the

right than to the left. Widhe [72] examined sagittalspinal shape and mobility in 90 children at 56 and

1516 years of age and found that kyphosis and lordosis

increased and mobility decreased, especially thoracic

extension.

Spinal mobility in scoliotic children

Poussa and Mellin [73] examined 71 girls with pro-

gressive AIS in three grades of severity for spinal mobil-

ity in the sagittal, frontal and transverse planes.

Thoracic rotation was most clearly decreased with

increased curves and, together with straightening of

the spine, was thought to be an important pathome-chanism of progressive AIS. Viola and Andra ssy [74]

examined children with structural scoliosis longitudi-

nally at the age of 5, 10 and 14 years and reported

non-physiological spinal mobility with forward flexion

increased between 510 years and decreased between

1014 years.

Implications for sagittal plane research

In assessing impaired movements in the thoracic

spine in early AIS, current attention is directed almost

exclusively to the sagittal plane where in health flexion-

extension is maximal at T12/L1. The above reports

suggest that before primacy is attributed to the sagittal

plane in aetiopathogenesis any impaired rotation or

deformity in the other two planes should be established.

primary rotation deformity?

Primary rotation deformity? (figures 1 and 2)

Roaf [45] suggested that all the phenomena of severe

scoliosis were explained solely on the basis of a primary

rotation deformity.

Intra-spinal and intra-discal axial deformity

Intra-vertebral and discal axial rotation have been

found in the scoliotic spine [52, 75, 76]. Posterior spinal

instrumentation and fusion can only correct the rota-

tional deformity of a scoliotic spine at the discs,

which is less than that within the vertebrae. The greatest

asymmetric intra-vertebral deformity has been found

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R. G. Burwell

Figure 1 Mechanism of axial rotation in a thoracic and a lumbarvertebra. Note the centre of axial rotation, anterior in the thoracicvertebra and posterior in the lumbar vertebra where it is associatedwith shear (from Gregersen and Lucas [177]).

Figure 2 Axial vertebral rotation in structural scoliosis. Note theposterior centre of axial rotation according to Adams. It is similarto that of Smith et al. [281], their figure 6, but different from that ofPorter [44] and Guo et al. [18], who place it in the vertebral canal(modified from Adams [282]).


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at the curve apex that diminished away from the

apex with symmetrical vertebrae at the neutral verte-

brae [77].

vertebral b ody growth platesthe vicious

cycle concept or growth-induced torsionconcepttraction tr eatment, a s ound

theoretical basis for brace treatment?

Anterior lateral shear forces and posterior torque

forces (figure 3).

Wever et al. [78] interpreted the vertebral deformities

of structural scoliosis to bone remodelling due to lateral

shear forces created in the anterior column driving the

apical vertebra out of the mid-line, whereas torque

forces created by posterior musculoligamentous struc-

ture attempt to minimize the deviations and rotations of

the vertebrae.

Vicious cycle concept or growth-induced torsion

concept(figure 4)

Roaf [45, 46] suggested that spinal imbalance (lateral

spinal curvature) through gravity and continuous mus-

cle action leads to asymmetrical loading of the vertebral

growth plates and, hence, to asymmetrical growth

that is in accordance with the Hueter-Volkmann law

[27, 39, 79, 80] (vicious cycle concept circular causality).

Perdriolleet al. [81] found no inter-vertebral movements

in the major curve of anatomical scoliotic specimens

and hypothesized that scoliosis from its onset was deter-

mined by a mechanical process termed torsion. The

change in orientation in both the frontal and sagittal

planes encouraged the redistribution of inter-vertebral

forces that tended to be located on the concave side ofthe curve and cause cuneal deformations of the verte-

brae; this resulted in further redistribution of forces

so that, after its onset, the spine was mechanically

unstable. In essence, structural scoliosis is a 3D rotatory

complex movement occurring mostly in the apical

region.

The view that cyclical eccentric forces on the verte-

bral end-plates in both frontal and sagittal planes with

vertebral growth modulation is the mechanism for AIS

(vicious cycle concept) is supported by most workers

[6, 9, 38, 6365, 80, 8284]. It provides the theoretical

basis for brace treatment [8083]. While girls scoliosiscurves are more likely to progress than boys, when

>30, progression may be similar in boys and girls [85].

Progression is not usually vicious, in that most

small curves stabilize and are benign. Moreover, since

its mechanical basis has been questioned [86], a better

description might be the growth-induced torsion concept.

While the factors that determine which curves progress

have been examined clinically in relation to prognosis

with some success [85, 8790], the underlying mecha-

nisms that determine curve, progression or stabilization

are unknown. The work of Guo et al. [18] suggests that

thoracic vertebral body shape and size and vertebral

proportions for age may be of critical importance to

curve progression.

143


Figure 3 The force pattern in the scoliotic spine (modified fromWeveret al. [78]).

Figure 4 Diagram of the vicious cycle concept by which eccentricloads act on immature vertebrae in a curved spine to cause a progres-sive torsional growth of vertebrae and discs. As most small curves donot progress, it would be better termed the growth-induced torsionconcept (modified from Stokes [80]).


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Is there a mechanism of deformation in AIS girls

intrinsic to anomalous thoracic vertebrae?

The recent finding of Guo et al. [18] that scoliosis

curve severity in AIS in girls correlated significantly

with the ratio of vertebral body height to pedicle height

at all thoracic levels is consistent with the viewthat an intrinsic anomaly involving endochondral

and membranous bone formation in all thoracic verte-

brae contributes to curve severity. This may involve

both relative anterior spinal overgrowth and spine

slenderness.

What is the biological mechanism in vertebrae

of the torsion?Chronic cumulative stress,

involving stress-activated protein kinases in

a calcium-dependent mechanotransduction

possible physiotherapy?

The mechanisms of growth modulation and the

effects of tethering on disc function and integrity

deserve further study [9, 82, 91, 92] and may involve

both the tonic action of muscles [45, 46] and the biome-

chanical stresses of everyday life [64]. In the latter con-

nection, the mechanical mechanism has been likened to

that of the chronic cumulative effect of repetitive biome-

chanical stresses of daily living applied unremittingly

and eccentrically to the 3D spinal deformity with its

malaligned immature vertebrae and discs [64]. This

possibility suggests that:

1. The biological mechanism may involve stress-activated protein kinases (SAPKs) released in

vertebral growth plates. SAPKs are important

regulators of a variety of repetitive loadings includ-

ing tendons and are evaluated by measuring c-Jun

N-terminal kinase (JNK) activation [93]a signal-

ling event in oxidative-stress-mediated cell death

protected or modulated by the selenium-containing

anti-oxidant enzyme glutathione peroxidase [94].

Such stress-activation appears to be mediated

through a calcium-dependent mechanotransduction

pathway.

2. Traction needs evaluating further as a treatment.

Stehbens and Cooper [95], after reviewing traction

as a treatment for IS, treated a child with juvenile

IS on a jungle gym (monkey bars) several times per

day with the swinging motion applying the stresses

equally to both sides of the body, with the weight

of the lower body providing traction, as well as

carefully selected exercises, with rapid improvement

within 10 weeks.

Platelets activated in a calcium-dependent mechanism?

A recent hypothesis [9698] relates to growth factors

liberated from platelets activatedalso a calcium-

dependent mechanismin deforming immature apical

vertebrae and which stimulate anterior spinal growth

in progressive AIS (skeletal hypothesis).

Does uncertainty about brace treatment question

its theoretical basis? Is the growth-induced torsion

a primary skeletal change?

In view of recent dubiety about the effectiveness of

brace treatment for AIS [86, 99, 100], Goldberg et al.

[86] asked if the vicious cycle hypothesis on which it is

based has no greater standing than any other hypothe-

sis? Their question has re-awakened interest in an

earlier concept that the structural changes in the scolio-

tic vertebrae may be aprimary skeletal change(intrinsic)[18, 27, 101, 102] rather than secondary to mechanical

factors.

Goldberg et al.s question is consistent with their

concept that IS results from developmental instability.

Goldberget al.s suggestion ignores clinical and experi-

mental knowledge that immature bones are readily

deformed by sustained asymmetric mechanical forces.

Compensatory scolioses or counter-torsions

As adjustments to torsions of the major curve(s), com-

pensatory curves presumably involve neuromuscular

mechanisms to balance the head above the natal cleft.

concept of a ligamentous check-rein, or tether,

to growth causing the spine to buckleloads,

neuromuscular response and treatment in

recumbency

Restraining ligaments

The possible role of the anterior longitudinal liga-

ment as a check-rein (like the periosteum of limb

bones) in limiting or permitting curve progression is

rarely discussed, and in this connection its innervation

may be relevant. Ponseti [103] and others [64] stated

that IS entails weakening of the powerful ligaments of

the vertebral and costovertebral articulations; unless

these ligaments weaken, vertebral rotation and, thus,

true scoliosis cannot take place in humans. This aspect

was recognized as a deficiency of a recent finite element

study that omitted ligamentous structures, articulations

and muscles [61].

144

R. G. Burwell


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Spinal growth creates a restraining growth

force in ligaments and dura

Kawabataet al. [104], in a mathematical study, tested

the hypothesis that when some vertebral bodies and

discs outgrow their surrounding soft tissues, such as

the ligaments and dura, a non-physiological growthforce is created acting to restrain with buckling most

easily when the growth force was localized from

T9L1. Suggested tethering of spinal growth by

posterior musculoskeletal structures is an example of

the action of a putative growth force altering spinal

geometry [6, 78] (figure 3).

Concept of the interaction of the initial spinal deformity

with the nervous systemtreatment in recumbency

Coillard and Rivard [38] suggested that minimal

deformity can alter intra-spinal loads and cause a

change in static and dynamic balance without a mor-

phological change in the spinal column. An inadequate

neurological response, muscular dysfunction or limited

ligamentary constraint could result in a cascade of

events with chaotic functioning, resulting in a change

of balance and a progressive deterioration. They note

that A reclining position over an extended period of

time was and furthermore remains in some countries

the best treatment for scoliosis, which worsens little

or not at all under such conditions [39, 46].

Important issues are: (1) what initiates the scoliosis

curve? and (2) is it possible to prevent the deformity

surgically? To achieve prevention, some knowledgeabout curve initiation may be helpful.

thoracic sagittal spinal sha pe changes in

health and AISin curve initiation are other

planes involved simultaneously?

Fixed lordotic area

Somerville [48] concluded that the scoliotic deformity

consisted of lordosis, rotation and lateral flexion arising

from failure of growth of the posterior elements of a

segment of the spine and suggested the term rotational

lordosis. This 3D view of structural scoliosis was sup-

ported by Roaf [40, 42, 45, 46]. Dickson et al. [105]

maintained that the essential lesion of idiopathic tho-

racic scoliosis was a fixed lordotic area which under the

influence of a transverse or coronal plane asymmetry,

rotates to the side and gives rise to a lateral curvature

(biplanar asymmetry concept). Millner and Dickson [6]

stated that the lordotic area being present before the

spine becomes deformed is the prime aetiology of IS.

In addition to lateral wedging, sagittal vertebral

wedging is a feature of the established curve [42, 106].

Somervilles view [48] that structural scoliosis is a 3D

lordoscoliosis is now generally accepted. The involve-

ment of the sagittal plane to permit the axial rotation

about a posterior axis is also generally accepted(figure 2). The controversy [6, 18, 78] relates to the

suggested primacy of the sagittal plane in initial patho-

genesis, i.e. curve initiation.

Simultaneous occurrence of the spinal deformity

in three planes

Xiong et al. [107] examined 96 AP and lateral radio-

graphs of girls of average age 13.8 years with scoliosis

curves of Cobb angles 130 divided by severity into

four groups. The results indicated the simultaneous

occurrence of the deformity in three planes and not

in any single plane. More research is needed to resolvethis controversy.

Hypokyphosisconcept of timing of adolescent growth

in relation to sagittal spinal shape changes and the

effect on axial rotational stability

Millner and Dickson [6], noting that the normal tho-

racic kyphosis diminishes during the pre-adolescent

growth period [108], write: At this time the girls are

growing and developing quickly, thus magnifying

any trend towards flattening of the normal thoracic

kyphosis. No evidence is provided to support this tim-

ing concept [14]. Dickson [109] explains: The thoracickyphosis is normally protected from buckling by being

behind the axis of spinal column rotation but when the

thoracic lordosis develops it brings the apical region

anterior to this axis and thus under compression with

resultant buckling of the spinal column ( rotationally

unstable) (figure 2).

Reviewing the field, Raso [110] concluded that,

while there is little scientific evidence that IS was due

to buckling of a hypokyphotic spine, the most likely

biomechanical factor based on accumulated circum-

stantial evidence was the development of a hypokypho-

sis, causing buckling of the spine. Such children, he

opined, are normal, but subtle growth differences

between the anterior and posterior aspects of the

vertebral body may lead to lateral buckling of the

spine (a possible contribution of the ribcage was not

considered in Rasos review). Stokes [111] stated that

the most likely biomechanical mechanism for the

aetiology of thoracic IS is hypokyphosis as a risk factor,

not a unique cause of IS. Grivas et al. [112] viewed the

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hypokyphosis as being permissive, by facilitating axial

rotation, rather than aetiologic in the pathogenesis of

IS. Some surgeons still implicate axial vertebral rotation

and small lateral curves in curve initiation. Lowe et al.

[14] concluded that there was no strong scientificevidence implicating any particular biomechanical

factor in the aetiology of IS.

Sagittal spinal profile and radiological declive and

proclive angles (figure 5)

Studies of the sagittal spinal profile [113] and the

radiological declive angle at T1112 in 37 school screen-

ing referrals mainly with small curves [114] are consis-

tent with the concept that hypokyphosis in some way is

a feature of the early pathogenesis of AIS.

Declive and proclive segments

Uyttendaele and De Wilde [115], in a study of 483

normal girls and boys aged 916 years, used Moire

topography and concluded that girls are more prone

to develop AIS because their spines, with a relatively

longer declive segment and a shorter and less inclined

proclive segment, have less capacity to neutralize

the rotation-inducing forces than does the spine in

boys.

Impaired forward flexion (IFF) in segments of the

lower thoracic spine

1. Tomaschewski [116], in 686 healthy schoolchildren

aged 910 years, used the forward bending test,

looked at the child from the side and reported

IFF in 16.5%. In the subsequent year, 27% were

reported to have developed a structural spinal defor-

mity, as judged clinically and radiographically.

2. Weiss and Lauf [117] extended these observations

to 614 healthy children aged 2, 4 and 5 years and

found IFF mainly in the lower thoracic region

in 7.9, 78.9 and 70.8% respectively, where the har-

monic arch of the trunk was interrupted by a

short vertebral segment which seemed straight

and could not actively or passively be bent or

flexed forwards. These workers concluded that

IFF, occurring before any trunk hump in the trans-

verse plane was the pre-selection condition for

development of IS. In particular, they suggested

that IFF in more than three motion segments

may destabilize the childs spine so that progressive

rotation and lateral deviation occur during periods

of rapid growth.

3. Schmitz et al. [118], in a 3D ultrasound topometric

study of 102 healthy children aged 79 years in

a maximally flexed position, detected seven childrenwith clinical signs of scoliosis and reduced flexion

in the middle to lower thoracic segments.

4. Nakakohji [119], in a radiological study, compared

93 children with IS with 40 controls and found

localized areas of a severely reduced range of

spinal flexion that was thought to contribute to

the pathogenesis of the spinal curvature.

Frontback asymmetry concept

The above findings are consistent with the view

that the idiopathic patient buckles on flexion [109].

Millner and Dickson [6] emphasized that, while

structural scoliosis is a complex 3D deformity, . . . the

problem is one offront-back asymmetry and not right

left. Cheng [18, 56] supported a loss of coupling in the

longitudinal growth between the anterior column

and posterior column. The crankshaft phenomenon,

especially in immature children and its prevention by

anterior spinal resection and epiphyseodesis [120, 121]

146

R. G. Burwell

Figure 5 Radiological segmental sagittal spinal profile in a 14-yearold girl with a left thoracic (LT) scoliosis of 49, apex T10. Note (1) thelordotic segment (LS), (2) the kyphotic angulation below it and(3) the backward tilt of T12 vertebra of 6

is much less than the con-trols at this vertebral level. The latter may make it more rotationallyunstable in the transverse plane (modified from Kiel et al. [114]).


11/34

is a graphic demonstration of the importance of rela-

tive anterior spinal overgrowth in curve progression.

However, rib hump reassertion in patients after poster-

ior Universal Spine System for AIS was explained

by unwinding the ribcage tensioned by surgery rather

than through relative anterior spinal overgrowth, i.e.the crankshaft effect [122].

Recent evaluation by models

Murray and Bulstrode [123] constructed a simple

model and showed that overgrowth of the anterior

column relative to the posterior column caused it to

take up the shape of an IS. Azegami et al. [124] showed

that a buckling phenomenon caused by relative anterior

spinal overgrowth could produce scoliosis, with the

predominance of right curves being attributed to the

heart being on the left. Examining buckling and bone

remodelling in a finite element model, Goto et al. [61]suggested that, while scoliotic changes are triggered by

the buckling phenomenon, this is counteracted by bone

formation, but worsened by resorption of loaded bone.

Preventive surgery?

Like the way anterior spinal surgery supported the

frontback spinal asymmetry concept, preventive sur-

gery to correct sagittal spinal shape may substantiate

the concept [125].

Comment on the frontback spinal asymmetry conceptThe evidence is consistent with the obligatory involve-

ment of the sagittal plane in the initiation of thoracic IS.

However, the primacy of the sagittal plane in curve

initiation is not established for children referred

after screening, the scolioses already have 3D defor-

mities [107] so that longitudinal vertebral growth

becomes eccentric leading to a growth-induced torsion.

Moreover, there is no substantial radiological evidence

to show that the other two planes are not simul-

taneously involved before the development of the lateral

curve [6, 109]. There are other concepts to explain the

initiation of a thoracic curve involving (1) the spine, (2)

the ribs (concave rib overgrowth) and (3) muscles.

The frontback asymmetry concept for thoracic

scoliosis does not explain or adequately explain [126]

(1)non-standard vertebral rotation[127], (2) the predom-

inant laterality of thoracic AIS and progressive IIS

curves, (3) the laterality ofleftright shapeof the normal

back that develops mainly during the pubertal growth

spurt at ages 1214 years [128130], (4) the widespread

leftright asymmetries in AIS subjects [101, 102, 131

141], (5) pelvic asymmetry [142] and (6) increased and

asymmetric femoral neck-shaft angles [143]. The front

back asymmetry concept invokes leftright asymmetry

(frontal plane and/or transverse plane) to cause scolio-

sis (biplanar asymmetry concept [105]). Leftrightasymmetry findings have provided the basis for three

multi-factorial concepts of etiology.

thoracolumbar and lumbar sagittal spinal

shape changes in AIS?

Millner and Dickson [6] write: For the sagittal plane

to be blamed primarily for thoracolumbar or lumbar

curves implies lordosis where the spine should be

straight (thoracolumbar region) or more lordosis than

normal (lumbar region) and evidence exists for both.

Lupparelli et al. [83] stated that lumbar curves were

characterized by dysharmonic evolution due to rotatorysubluxation phenomena with stability provided by the

lumbar facet joints that restrict axial rotation (figure 1).

Raso [110] commented that little work has been done

on the aetiology of lumbar scoliosis. The lack of aetiol-

ogic knowledge about these curve types suggests that

the mechanism at work is not yet understood for any

of the curve types. The mechanism may be a primary

skeletal or ligamentous change or result from segmental

neuromuscular imbalance that will now be discussed.

primary skeletal change, ligamentous change

or segmental neuromuscular imbalance for theinitiation of AIS?JIS and othe r asymm etries

In thoracic AIS, the growth-induced torsion concept

requires a sustained alteration of normal spinal geome-

try in one or more segments about the future apex of

the curve, so that normal linear vertebral growth is

converted to that of torsion (growth-induced torsion

concept). The theoretical requirement is for the centre

of axial rotation of certain thoracic vertebrae to move

posteriorly in order to explain the pattern of axial

rotation in thoracic scoliosis [6] (figures 1 and 2).

Once this segmental change in the thoracic spine has

occurred, the mechanical process of torsion is generallythought to predominate, but it may be influenced by

neuromuscular mechanisms.

The basic biological process that initiates sagittal

spinal shape change is unknown. It is not apparently

discogenic and could be:

1. A primary skeletal change [27] involving uncou-

pling of growth between the anterior column and

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12/34

posterior column of the spine [18, 48, 56], where

vertebral growth creates the maturational sagittal

spinal shape changes.

2. A primary ligamentous change [27] affecting

posterior spinal structures [48].

3. A segmental neuromuscular imbalance creating abiomechanical susceptibility to the growth-induced

spinal torsion of AIS.

4. A combination of two or more of the abovethis

would be consistent with the concept of develop-

mental instability for AIS.

Option (1) suggests that an uncoupling within the

columns of the thoracic spine may initiate the hypoky-

phosis of health and the fixed lordotic area of IS.

In AIS, of all curve types any primary skeletal change

could occur segmentally in one or more planes to create

the main (primary) curve without any extrinsic factors

being involved. The difficulty is refuting the concept.Option (3) for AIS will now be outlined.

A segmental neuromuscular imbalance causing

a maturity risk factor?

The observations of Guo et al. [18] did not show any

apical lordotic area in contrast to those of Deaconet al.

[43]; this may be due to Guoet al. not using true lateral

projections of the spine.

In the thoracic region there is an obligatory need

for the sagittal plane to be involved so as to overcome

the kyphosis control of axial rotation [6]. A prudent

speculation is that of a maturational change in the

form of a segmental neuromuscular mechanism (as a

scoliogenic lesion [129]); by causing sustained segmental

changes of geometry in a slender spine when combined

with the rapid growth spurt of adolescence makes

it biomechanically susceptible to deformation by tor-

sion [6]. This mechanism by creating a maturity risk

factor could operate in each of the thoracic, thoraco-

lumbar and lumbar regions of the spine, with curve

laterality being determined by developmental mecha-

nisms in the CNS [144].

Dubousset and Machida [145] incorporated a neuro-

muscular imbalance in their neurohormonal concept of

AIS. The putative segmental neuromuscular imbalance

concept was consistent with conclusions about the

role of the nervous system in the aetiology of AIS.

Although, like the primary skeletal change concept,

the present difficulty is refuting it, there are ways of

evaluating any neurodevelopmental disorder.

Other types of AIS

The concept of segmental neuromuscular imbalance

explains the different lordotic patterns associated with

each of the single structural curve, double curves

and triple curves [146] as a function of aberrant neuro-

muscular activity, as well as other curve types nowdefined in the new classifications of AIS.

Juvenile idiopathic scoliosis

The concept of segmental neuromuscular imbalance

explains JISdiagnosed during a period of slower

spinal growthas needing either:

(a) earlier and stronger neuromuscular imbalance to

initiate a curve than in the presence of the adoles-

cent growth spurt, and/or

(b) greater primary vertebral morphological features.

Other asymmetries

Skeletal asymmetries detected at other sites may be

explained by neuromuscular imbalance involving CNS

control.

a short spinal cord i nducing neurovertebral

growth disparity? However, in syringomyelia

cord tetheri ng occurs without a predominant

scoliosis laterality

In the 1960s, Roth proposed the hypothesis [147],

rediscovered by Porter [44, 47], that when spurts of

elongation of the spine are too rapid for the slowergrowth rate of the spinal cord and nerve roots, the

neurovertebral growth disproportion is compensated

for by adaptive scoliotic curvature of the otherwise nor-

mally growing spine. Porter [47] suggested that the

spinal cord may fail to stretch in response to vertebral

growth due to molecular mechanisms with melatonin as

a powerful anti-oxidant protecting against cellular

damage. These novel concepts involving biorhythms

need testing [147]. Machida and colleagues [145, 148,

149] implicate melatonin in the aetiology and treatment

of AIS. The neurodevelopmental concept for AIS

outlined below also suggests a trial melatonin and

other substances.

Cord tethering and Chiari malformation appear to be

major causes of syringomyelia and scoliosis. However,

the laterality of these curves was about equal, right

and left [150], so, if cord tethering in syringomyelia

does not cause a predominant laterality for the associ-

ated scoliosis, how can a short spinal cord explain the

laterality patterns of AIS?

148

R. G. Burwell


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small right thoracic curvespredisposing to

scoliosis curve form ation?

White [151], noting the presence of a physiological,

slight right thoracic curve [52], suggested that if the

precarious balance of the normal thoracic motion is

disturbed, vertebrae in the slight curve might somehowrotate too much into the convexity of the curve. The

concept has been rejected [152, 153].

left lateral thoracic curvesdisease or

developmental biology?

Disease and developmental biology

Goldberget al. [154], in reviewing left thoracic curves

and their association with disease, concluded that

gender in males and age at diagnosis in females are

more important risk factors.

The gender and age effect was confirmed by Grivas

et al. [155] in a school screening sample who found that

girls before menarche had significantly more left curves

(10 or more) and after menarche more right curves.

This finding supports the view that left curves result

from a natural mechanism which determines left/right

laterality [129] rather than being an aberration from

the right bias in development due to putative stressors

[137, 138].

concepts for curve laterality in

AIS & IIScontroversy

The problem of curve laterality, like that of cerebral

laterality with a strong bias towards right-handedness

[156, 157], is complex and controversial.

Neural-, visceral- and diaphragmatic-determined curve

laterality (directional asymmetry)

Several causes had been invoked to explain why AIS

curves are predominantly right-sided, including handed-

ness (Sabatier), the heart (52), the aorta (Bihat, adopted

by Taylor [158] and Millner and Dickson [6]), a larger

right lung [159] and the diaphragm (Jansen).

Handedness

The relation of handedness, a behavioural marker of

early neurodevelopment, to curve laterality in AIS was

addressed in two recent studies [144, 160], but remains

unresolved.

Developmental biology

The pattern of the common right thoracic curve

and less common left thoracic curve of AIS has been

attributed to one of two developmental concepts:

1. Physiologic from nature. The pattern of spinalasymmetry during normal development is explained

by the hypothesis of oscillating axial torsion [129],

with an early bias to the left and a later bias to the

right; in a minority of the population the opposite

occurs. Patterns of leftright asymmetry observed

in each of pedicle lengths [52, 53, 158, 161, 162],

spinal mobility in the transverse plane [71], small

thoracic spinal curves, back contour asymmetry

[128130] and skeletal limb asymmetries [101, 102,

126, 139141] are explained by this physiological

concept; it also explains the left laterality of

progressive IIS and the predominant right thoracic

AIS. Taylor [158] suggested that vascular asymme-tries probably determine the direction of a scoliosis

but could not account for plagiocephaly and limb

length asymmetries.

2. Aberrant from nurture. Goldberg et al. [137, 138]

hold that right thoracic curves of AIS are due

to an increase of the normal bias to the right and

left convex curvesthat are not secondary to some

pathologyare stress-induced, causing reversed

asymmetry or low directional asymmetry but

high stress resulting in antisymmetry, or random

leftright distribution.

continuous spinal realignment and position

sensing in h ealth

Spinal stability as a mechanical process involves con-

tinuous realignment of the spine based on position-sen-

sing at the motion segment level and involving the head

and trunk as well as the spine [14]. Lowe et al. [14]

pointed out that this dynamic process might lead

to the development of scoliosis in the presence of an

initially normal biomechanical structure, and research

efforts to validate this dynamic concept have only

recently been initiated [163].

Thoracospinal concepts

thoracic cage functions in health

and after surgery

The outstanding function of the thorax is respiration

using various muscles. However, no less important is

the support of the spine [39, 164] in standing, sitting,

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gait and other activities, thereby controlling the move-

ments of the thorax on the pelvis and providing origins

for the muscles which run from the thorax to the

scapulae and arms. The ribs restrict axial rotation in

the thoracic spine [48]. Gardner [165] emphasized the

importance of the whole body wall in the pathogenesisof IS and particularly how (1) the mid and upper

ribs are a significant barrier to the surgical vertebral

derotation and correction of the upper rib hump and

(2) the sternum acts as the fourth column in stabilizing

the spine.

rib deformity in AIS

The rib deformity in scoliosis is discussed by Erkula

et al. [166]. Many workers hold the view that the rib

deformities of progressive AIS are adaptations to forces

imposed by the scoliotic spine [78, 167] with the

sternum, held nearly stationary by abdominal ties andproviding the opposing forces needed to deform the ribs

[168]. In scoliosis, the ribs may act as a couple to

increase rotation [45].

Some workers have attributed the initial spinal

deformity of AIS to changes in ribs [39, 79, 112, 164,

169174], with subsequent deformity resulting from

growth-induced torsion.

ribcage in th e frontal planethe Nottingham

(ordinner plate-flagpole) conceptscoliosis

initiation by combined rib and spinal mechanisms

The pioneering prognostic work on the rib-vertebra

angle difference (RVAD) in infantile IS by Mehta,

in juvenile IS by Tolo and Gillespie and subsequent

publications will not be discussed here. In AIS,

RVADs are not prognostic.

The Nottingham (or dinner plate-flagpole) concept

femoral anteversion, sagittal spinal profile, the ribcage,

gait and scoliosis (figures 6 and 7)

This concept [39, 79, 169, 170] proposes that thoracic

AIS results from a puberty-related developmental

abnormality in the central nervous system that creates

rib-vertebra angle asymmetry (in the frontal plane)which, with spinal mechanisms, initiates the curve [39,

79, 169, 171, 172]. In association with a short segment

lordosis, this leads to a cyclical failure of mechanisms

of axial rotation control in the trunk that involves

(figure 6):

1. A pelvi-spinal rotation-inducing system(lower limbs

and pelvis), and

2. A rotation-defending system (thoracic kyphosis,

discal, costal and neuromuscular mechanisms

acting on the spine and ribs) in gait and other

activities in which a mechanical breakdown of

axial rotation creates the initial deformity of IS

(failure of rotation control) (figure 7)

150

R. G. Burwell

Figure 6 Drawing to show the dynamics in gait of the skeletalframework as a basis for the Nottingham thoracospinal concept ofaetiopathogenesis of AISalso known as the dinner plate-flagpoleconcept or better dinner plate-tentpole concept. The pelvis is likenedto a dinner plate and the spine to a flagpole or tentpole. Thegap between the upper spine and lower spine represents the transi-tional point (displacement node) above which axial rotation is inthe direction opposite to that below [177]. In the thoracic spineaxial rotation is maximal about T7 and minimal at the lower threelevels. See text and Gregersen and Lucas (modified from Burwell[178]).

Figure 7 Schematic drawing to show the gait-driven spinal rotation(Nottingham) concept for AIS. See text (modified from Burwell

et al. [175]).


15/34

The concept was based on studies in each of femoral

anteversion (FAV) [169, 175, 176], the radiological

declive angle at T11/T12 [114] (figure 5), the normal

ribcage [170172] (figure 8) and the biomechanics

of gait [52, 177] (figure 6).

Growth-induced torsion concept

The growth, both abnormal (secondary to vertebral

hyperpressures) and normal (linear spinal growth) with

gravity and muscle forces adds to the initiating and

continuing neuromuscular mechanisms to augment

curve progression (figure 4), i.e. the growth-induced

torsion concept.

Subsequently [178, 179], Burwell and his colleagues

considered that scoliosis curve progression was deter-

mined by how much the immature vertebrae remodel

under eccentric loading created by putative neuromus-

cular imbalance in the trunk in the presence of gravi-

tational and growth forces. The sagittal plane rib

asymmetry evidence reported by Grivas et al. [112] is

consistent with the Nottingham concept of pathogene-

sis. Most recently, it has been suggested that growth

factors liberated from platelets activated in deformingvertebrae may induce relative anterior spinal over-

growth in progressive AIS [9698]. A comparison of

gait patterns in AIS girls with controls revealed balance

problems during the stance phase and asymmetry

in frequency characteristics that was thought may

be a primary effect contributing to the medio-lateral

deformity of the spine [180].

Do the patterns of RVADs in the normal thorax

reveal an aetiologic factor and a biomechanical

susceptibility to progressive IS?

Figure 8 shows that, in normal chest radiographs

from 412 children, the patterns of RVADs reflect the

age, sex and side patterns of progressive IS. It is as

though a proportion of these children had progressive

scolioses, yet none had a scoliosis of 5 or more. In the

puberty group, the adolescent girls show significantly

more rib drooping at levels 47 on the left than

on the right to produce the pattern of the RVADs.

In contrast, the boys in puberty show no detectableRVA asymmetry that is consistent with the lower

male prevalence of progressive thoracic AIS. It was

suggested that RVA asymmetry provides a biomecha-

nical susceptibility or maturity risk factor to AIS, JIS

and IIS.

ribcage in the transverse planeSevastiks

thoracospinal conceptscoliosis initiation by

concave periapical rib overgrowth

Sevastik and colleagues [173, 174] adduced experi-

mental, anatomical and clinical evidence for his thora-

cospinal concept that applies only to adolescent girls

with right thoracic AIS. It involves dysfunction of

the autonomic nervous system [174, 181] that causes

increased vascularity of the left anterior hemithorax

resulting in overgrowth of the left ribs. This in turn

disturbs the equilibrium of the forces that determine

the normal alignment of the thoracic spine and triggers

the thoracospinal deformity simultaneously in the three

151


Figure 8 Segmental RVADs (rib-vertebra angle differenceRVA asymmetry in the frontal plane) for infancy, childhood and puberty agegroups. Statistical analyses are for sex (p/sex) and asymmetry (p/asymmetry) Probabilities of significance * 0.01


16/34

cardinal planes [107] (linear causality concept). Colour

Doppler Ultrasonography did not find any evidence for

side differences in vascularity of the anterior thoracic

wall in right thoracic AIS girls, thereby not justifying

the vascular component of Sevastiks concept [182].

Growth-induced torsion concept

Sevastiks concept does not deal with the factors

involved in the progression of the curve which he con-

siders to be of a biomechanical nature [174], i.e. the

growth-induced torsion concept.

Sevastiks concept has been applied surgically with

early success in a 7-year old girl with a right thoraco-

lumbar IS [183]. Finite element models support such

early intervention on the ribcage to prevent curve pro-

gression in small-to-moderate IS [184].

Skeletal growth maturity indicators, certain

hormones and the saltatory hypothesis of

normal growth and maturation

Risser [185], in a study of 296 patients, observed a

direct relationship between vertebral growth and incre-

asing spinal deformity, a view previously supported by

Somerville [48] and subsequently discussed at the Third

Zorab Symposium in 1970 [27]. There are now many

facts to establish that spinal growth is associated with

the initiation and progression of AIS [9, 18, 21, 89, 120,

121, 125, 139, 186191]. An important finding is the

strong correlation of factors that predict the potential

residual skeletal growth and curve progression [191].

maturity indicators for age

The currentmaturity indicators for ageinclude chron-

ological age, menarcheal status, bone age (Risser sign,

triradiate cartilage, less commonly ischial apophysis

and hand and wrist bones) and Tanner stage of sexual

maturity [192196].

growth velocity patterns and importance

of oestrogen in boys and girls

Infancychildhood puberty growth model

A biological basis for the grouping of IS into infan-

tile, juvenile and adolescent types is found in the

infancychildhoodpuberty (ICP) growth model of

Karlberg and colleagues [197, 198]. The infancy com-

ponent starting in mid-gestation and continuing up to

34 years of age is believed to represent the post-natal

continuation of foetal growth. Thechildhood component

corresponds basically to the effect of growth hormone.

Thepuberty component most likely describes the part of

the adolescent linear growth stimulated by oestrogen in

both boys and girls [57, 199, 200].

AIS

Duval-Beaupe` re [186] showed that the progression of

IS occurred at the time of the most rapid adolescent

growth spurt but curve progression continued after

peak height velocity. She concluded [186] that there

is no cause and effect relationship between growth of

the vertebral column and scoliosis, except as contem-

poraneous phenomena. This conclusion provided the

bedrock for the mechanical growth-induced torsion

concept [81]. In brace-treated patients, greater progres-

sion was related to periods of rapid-to-moderate growthin the spine [191]. Curve progression decelerates after

the completion of skeletal maturity [186], but may

continue through adult life [89, 201].

Ha gglund et al. [198] found that AIS girls had an

above average height 2 years before the onset of the

pubertal growth spurt that did not persist. Willner

[188] reported that the growth velocity was elevated in

the year before the onset of the curvature attributed to

higher growth hormone secretion than in normal girls

[189, 198]. Veldhuizenet al. [33] could not demonstrate

any difference in growth increments of vertebral bodies

involved in the scoliotic curve compared with the rest of

the vertebral column. Goldberg [21] and Cole et al. [139]reviewed the few longitudinal studies of skeletal growth

in AIS subjects and noted (1) an earlier age at peak

height velocity (PHV) and (2) a significant increase in

PHV. Goldberg [21] concluded that it is now generally

agreed that skeletal growth was a significant factor

contributing to the natural history and prognosis of

AIS. Although growth mechanisms are assumed to act

directly on the immature vertebrae in curve pathogene-

sis, anindirect biomechanical mechanism of curve patho-

genesis has also been suggested [39, 139, 170]; this

concept involves a large extrathoracic skeleton and a

normal chest width.

Goldberg et al. [187] found that the mean age at

diagnosis for progressive curves is at the start of the

acceleration phase of the growth spurt (figure 9). In

contrast for stable (non-progressive) curves, the mean

age at diagnosis is after the peak height velocity and

Goldberg asked, Is rising growth rate the trigger

for curve progression? This begs the question, What

causes the rising growth rate of adolescence?

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puberty, growth hormone, sex ste roids and

gonadarche

The effects of growth hormone in juveniles is supple-

mented by sex steroids in adolescence [57, 197200,

202]. Adolescence begins with puberty, or more techni-

cally with gonadarche, which is an event of the neuren-

docrine system. Normal puberty is a consequence of

resurgence of episodic gonadotropin-releasing hormone

(GnRH) from the hypothalamus to receptors in theanterior lobe of the pituitary that release luteinizing

hormone (LH) and follicular stimulating hormone

(FSH) which, in turn, stimulate oestrogen and androgen

secretion. Puberty can be delayed or switched off by

down-regulating the receptors to GnRH in the anterior

pituitary by gonadorelin analogues [200]. How may this

relate to scoliosis treatment?

possible ther apeutic delay of the a dolescent

growth spurt in AIS subjects by gonadorelin

analogues

Two groups of workers have suggested the possibility

of using a gonadorelin analogue to delay the onset of

puberty in girls with AIS [203205].

NOTOM hypothesis and a gonadorelin analogue

(figure 10)

Burwell [203] gave the name neuro-osseous timing

of maturation (NOTOM) hypothesis to Nachemsons

concept [206] that there are more girls than boys

with progressive AIS for the following reason. The

maturation of postural mechanisms in the central

nervous system is complete about the same time in

boys and girlsfor which there is some evidence,

but the age and sex effect of postural sway in

healthy children needs further evaluation [207212].

153


Figure 9 Height velocity (cm/year) plotted against age to show the relationship between diagnosis and growth rate for progressive and stable(non-progressive) AIS shown years before menarche (1, 2, 3) and after menarche (1, 2, 3). Note that the earlier onset of the progressive curvesoccurs in the acceleration phase of the adolescent growth spurt when there is more residual growth (modified from Goldberg et al. [187]).

Figure 10 Neuro-osseous timing of maturation (NOTOM) hypothe-sis for AIS pathogenesis. Height velocity (cm/year) plotted against agein relation to putative postural maturation at 12 years. Note the earlieradolescent growth spurt (AGS) in girls in a phase of postural imma-turity and later in boys in postural maturity (modified from Burwell[203]).


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Girlsperhaps due to natural selection in evolution

enter their adolescent growth spurt before their postural

mechanisms are mature, so that if they have a predis-

position to develop a scoliosis curve, the spine deforms.

In contrast, boys do not enter their adolescent growth

spurt until their postural mechanisms are mature, sothat they are protected from developing a scoliosis

curve (figure 10). Burwell proposed administering a

gonadorelin analogue to delay menarche and slow

bone growth, as in boys and girls with idiopathic preco-

cious puberty. Expert scrutiny and conditional support

for this proposal has been obtained (Dr D. I. Johnston,

personal communication; Dr P. C. Hindmarsh, perso-

nal communication; Professor M. A. Preece, personal

communication).

Most recently [213], the NOTOM hypothesis was

evaluated in relation to the delayed puberty of ballet

dancers with thoracic curves [214] and rhythmic gym-

nasts with thoracolumbar and lumbar curves [215]. Itwas concluded that the NOTOMhypothesis is not nul-

lified, as there are discernible constitutional factors

(physique and laxity) and environmental factors (life

style and nutrition) in these particular sports-associated

scolioses that may render them non-idiopathic [213].

More research is needed.

Timing of the adolescent growth spurt in puberty and

a gonadorelin analogue

King [205] suggested the use of Lupron (a gonador-

elin analogue) to delay the onset of the adolescent

growth spurt. Lupron is used for the treatment of

precocious puberty and works by blocking the release

of FSH that in turn blocks the release of oestrogen.

The concept underlying this proposed treatment for

progressive AIS is that girls begin their adolescent

growth spurt at the onset of puberty, whereas boys

are in advanced puberty before entering their adolescent

growth spurt. Therefore, the adolescent growth spurt

in boys is superimposed on a more mature and pre-

sumably more stable spine. In girls, delaying the onset

of the adolescent growth spurt by 12 years in girls

could mean that the adolescent growth spurt would

be superimposed on a more mature and more stablespine.

why do only a proportion of girls develop

progressive AIS?

Both of the above concepts explain why there

are more girls than boys with progressive AIS, but

neither explains why only a proportion of girls develop

progressive AIS. One explanation is outlined below,

namely: a neurodevelopmental mechanism developing

in susceptible girls with spine slenderness associated

with ectomorphy leads to the initiation of AIS with

progression determined by mechanical factors including

spine slenderness.

melatonin defici ency as a causativ e factor?

Neurohormonal concept of Dubousset and Machida

Machida and colleagues [145, 148, 149], having found

lower plasma melatonin levels through 24 hours only in

progressive AIS curves (n 12) concluded that melato-

nin disturbance has more of a role in progression than

in the cause of IS. They postulated that, in the devel-

opment of progressive AIS, melatonin acts through the

nervous system. Dubousset and Machida [145], after

experiments on pinealectomized bipedal rats, suggestedthat IS may be:

. an inherited disorder of neurotransmitters from

neuro-hormonal origin affecting melatonin,

. associated with the bipedalcondition,

. when a horizontal localized neuromuscular imbal-

ance with torsion starts, and

. it produces a scoliotic deformity of the fibro-elastic

and bony structures of the spine.

The hypothesis that melatonin deficiency is a causa-

tive factor of AIS was not confirmed by several workers

but has by others. Reinker [216] concluded that it seemsunlikely that IS results from a simple absence of mela-

tonin. Rather, scoliosis could result from alteration in

the control of melatonin production, with either direct

or indirect consequences upon growth mechanisms.

the saltatory hypothesis of normal growth

Normal growth and growth-maturation

saltation episodes

Lampl [19] reviews evidence that growth is not linear

but occurs in saltations and stasis, with the saltations

(Latin leap) being accompanied by changes in

behaviour. The saltation and stasis hypothesis was

generated on time-intensive longitudinal data of infant

recumbent length. The protocol of daily measurements

has been applied to height during childhood and

adolescence with similar results. Infants and adolescents

have more frequent growth saltations than occur in

childhood [19].

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pubertysaltatory hypothesis, maturation in

the spin e, thorax and nervous systemmaturity

risk factors, saltations and possible significance

for IS

The saltatory hypothesis led to the concept that

growth is more than an increase in size and should beviewed also in terms of the maturationof the child dur-

ing puberty. The maturation changes in health that

may be of relevance to AIS aetiology are in vertebrae,

intervertebral discs, the spine, ligaments, the thorax,

pelvis and nervous system. These changes are separate

from maturity indicators.

Maturation in the normal spine during puberty

includes:

1. Vertebral body slenderness, disproportionate

anteriorposterior vertebral growth and thoracic

sagittal spinal shape changes [6, 18, 26, 32, 33, 70,

71, 108, 113119].2. Ligament [14] and disc [68] changes.

3. Spinal mobility changes [7074].

4. Ossification asymmetry in neural arches [158, 161,

162].

5. The laterality of small normal spinal curves.

Maturation in the normal thorax during puberty

includes:

1. Proportions of width/height [170, 172].

2. Rib-vertebra angle asymmetry in girls [171, 172].

3. RVADs in girls [171, 172] (figure 8).

4. Putative rib length asymmetry [173, 174] associated

with small thoracic curves.

5. Back contour asymmetry [128130].

Maturation in the nervous system during puberty

includes or may include:

1. Postural maturation changes involving neuromus-

cular mechanisms [207212].

2. Putative neuromuscular imbalance creating the

thoracic hypokyphosis.

3. Putative neurodevelopmental changes affecting the

CNS in the rapidly growing adolescent girls spine

involving lipid peroxidation.

Maturity risk factors, saltations and possible

significance for IS

Some of these maturational changes in the spine and

thorax with age are thought by some workers to be

biomechanical susceptibilities, or maturity risk factors,

to AIS during the adolescent growth spurt.

The salutatory hypothesis [19] needs testing in IS

subjects. Should saltations be detected then considera-

tion should be given to whether the effect of each

saltation on the trunk depends on the maturational

state of the spine, ribcage and nervous system, each of

which may have changed since the previous saltationfavourably or unfavourably with respect to suscepti-

bility to AIS. This concept could then be likened to a

machine gun (growth saltations) hitting a moving target

(maturation for example of the spine, ribcage and spinal

cord) (machine gun-moving target concept).

Tissue concepts

nervous system

Younger children with IS

MRI has revealed neuranatomical abnormalities in

20% of younger children with putative IS and curves

of 20 or more [217, 218].

Possible neuromuscular disorder in AIS?

The possibility that AIS aetiology involves unde-

tected neuromuscular dysfunction is considered likely

by several workers [11, 12, 14, 15, 17, 39, 56, 79, 126,

145, 148, 149, 169, 174, 178, 179, 181, 217, 219222] but

denied by Goldberg [223].

Lowe et al. [14] concluded that:

The current thinking is that there is a defect of centralcontrol or processing by the central nervous system thataffects a growing spine and that the spines susceptibility

to deformation varies from one individual to another.Girls may be more vulnerable to this process becauseof the short and rapid adolescent growth of the spinecompared with that in boys.

Loweet al. [14] stated that the most consistent clinical

studies point to the pontine and hindbrain regions as

the likely sites of primary pathology that could lead

to IS.

Postural maturation and neurodevelopmental

trunk size adaptations in puberty

Postural sway in healthy children needs further eva-

luation [207212].

A new neurodevelopmental concept for AIS

The putative neurodevelopmental maturational

changes in the thoracic region of the healthy childs

trunk during puberty have been expanded into a new

neurodevelopmental concept for AIS.

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muscles

The role of muscles in the aetiology of ISdespite

much research using electromyography, histochemistry

as well as mechanical and more recently finite element

modelsis unclear [224]. Three areas of current study

are outlinedat the hip, paravertebral muscles andplatelets as minimuscles.

Hip abductor muscles

Professor T. Karski (personal communication) pro-

vides the following account of his concept: There are

three stages in the development of idiopathic scoliosis:

(1) an abduction contracture, in reality a limitation of

adduction, mostly of the right hip; (2) a disturbance in

growth of the pelvi-sacral-lumbar region with the devel-

opment of a left lumbar scoliosis; and (3) the develop-

ment of a right thoracic scoliosis. . . . Detection of the

hip contracture in children aged 610 years and treatingit effectively with stretching exercises, and in some

patients surgery, slows the development of severe

scoliosis in adolescents and cures small curves in small

children [225].

The rotational preconstraint

A model to clarify the role of paravertebral muscles

provides a novel view of some scolioses [226]. The

hypothesis tested is that paravertebral muscle imbal-

ance with interference of the postural reflexes and

the body-weight related vertical loading leads to the

formation of a scoliosis curve.On an educational plastic human spine with the pelvis

constrained, multifidus from T110 on the right is

simulated by elastic rings causing a rotation. The

induced rotation of the upper spine is returned to the

frontal plane by springs attached to horizontal rods

and constrained by exerting a torque against the action

of all elastic rings (simulating postural correction);

then vertical loading (simulating upper body weight)

deformed the prepared section of the spine into a right

thoracic scoliosis. It was concluded [226] that hyper-

function of all the paraspinal muscles on one side pro-

vides an explanation for the rotation, frontal and

sagittal flexions of IS with subsequent remodelling(vicious cycle concept).

Platelets as minimusclesplatelet calmodulin and

modulation by melatonin

Over the last 20 years, from studies of patients with

IS, the concept has emerged that platelets act as mini-

muscles, with calcium kinetics, intracellular structure

and contractile protein activity similar to those of ske-

letal muscle [1].

Research on platelet calmodulin levels in AIS led

Lowe et al. [227] to conclude that the platelet is a

mini skeletal muscle with a similar protein contractile

system (actin and myosin) and suggest that calmodulinacts as a systemic mediator for tissues with a contractile

system (actin and myosin) [9698, 227a]. (Platelet

calmodulin has not been used hitherto in platelet

research, S. Heptinstall, personal communication.)

Melatonin binds to calmodulin with high affinity and

has been shown to act as a calmodulin antagonist [216,

224, 227].

ligaments

Increased ligamentous laxity has been described in

AIS, but Lowe [224] concluded that there is little evi-

dence that it is an important aetiologic factor. Taylor

and Melrose [66] commented that, at present, there

seems little point in pursuing the examination of con-

nective tissues from patien

Aetiology of Idiopathic Scoliosis. Current Concepts , Burwell

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