Open Access
Open Peer Review

This article has Open Peer Review reports available.

How does Open Peer Review work?

Association between adolescent idiopathic scoliosis prevalence and age at menarche in different geographic latitudes

  • Theodoros B Grivas1Email author,
  • Elias Vasiliadis1,
  • Vasilios Mouzakis1,
  • Constantinos Mihas1 and
  • Georgios Koufopoulos1
Scoliosis and Spinal Disorders20061:9

DOI: 10.1186/1748-7161-1-9

Received: 13 March 2006

Accepted: 23 May 2006

Published: 23 May 2006

Abstract

Background

Age at menarche is considered a reliable prognostic factor for idiopathic scoliosis and varies in different geographic latitudes. Adolescent idiopathic scoliosis prevalence has also been reported to be different in various latitudes and demonstrates higher values in northern countries. A study on epidemiological reports from the literature was conducted to investigate a possible association between prevalence of adolescent idiopathic scoliosis and age at menarche among normal girls in various geographic latitudes. An attempt is also made to implicate a possible role of melatonin in the above association.

Material-methods

20 peer-reviewed published papers reporting adolescent idiopathic scoliosis prevalence and 33 peer-reviewed papers reporting age at menarche in normal girls from most geographic areas of the northern hemisphere were retrieved from the literature. The geographic latitude of each centre where a particular study was originated was documented. The statistical analysis included regression of the adolescent idiopathic scoliosis prevalence and age at menarche by latitude.

Results

The regression of prevalence of adolescent idiopathic scoliosis and age at menarche by latitude is statistically significant (p < 0.001) and are following a parallel declining course of their regression curves, especially in latitudes northern than 25 degrees.

Conclusion

Late age at menarche is parallel with higher prevalence of adolescent idiopathic scoliosis. Pubarche appears later in girls that live in northern latitudes and thus prolongs the period of spine vulnerability while other pre-existing or aetiological factors are contributing to the development of adolescent idiopathic scoliosis. A possible role of geography in the pathogenesis of idiopathic scoliosis is discussed, as it appears that latitude which differentiates the sunlight influences melatonin secretion and modifies age at menarche, which is associated to the prevalence of idiopathic scoliosis.

Background

A wide range of Adolescent Idiopathic Scoliosis (AIS) prevalence in different countries is demonstrated by the various reports in the literature. (1–20) The significance of this specific observation may not be obvious but its evaluation is important because it could be related to a possible contributory factor of AIS pathogenesis.

In studying variations on the rate of sexual development across the world, a similar observation is recorded for the age at menarche, as well. (21–53) The influence of the geography of a specific region on human biology is determined by socioeconomic and environmental factors such as temperature, humidity and lighting that are transferred and expressed in human cells by specific mediators. (54) Age at menarche is definitely a biologic event and is considered a reliable prognostic factor of AIS. (55, 56)

The aim of this report is the study of IS prevalence and age at menarche as it is reported on published papers from different countries in various geographic latitudes and the investigation of a possible association between them that may reveal their possible role on AIS pathogenesis.

Methods and material

The inclusion criteria for the epidemiological studies were clearly defined before performing a search of the literature on scoliosis prevalence and on age at menarche by browsing the Medline database. The geographic latitude of each centre where a particular study was originated was documented. The included studies cover the whole spectrum of geographic latitudes in the northern hemisphere.

The scoliosis prevalence

A paper was considered eligible for inclusion when the study was reporting the prevalence of AIS among normal girls, was age matched, involving girls between 10 and 14 years old, the curves were detected through screening programs and a cut-off point of 10 degrees of Cobb angle was used for AIS definition. Twenty peer-reviewed papers met those criteria and were included in the study [120].

The age at menarche

Thirty three peer-reviewed papers reporting on age at menarche in normal girls at certain geographic regions were found and were included in the study [2153]. All the included papers are reporting the age at menarche of normal girls and not of specific groups.

The statistical analysis

The prevalence of idiopathic scoliosis and age at menarche were treated as the dependent variables in a linear regression forward modeling procedure. The geographic latitude of each location where the study had taken place was the candidate independent variable. Because of the different sample size of each study, frequency weights were used in the regression model, controlling for the impact of each latitude value, according to their sample size. The F-test of significance of overall regression and Type I partial F-test were calculated at a significance level less than 0.05, testing for the significance of overall regression and for each variable added during the modeling. A graphical analysis of the residuals of the regression was performed in order to detect potential problems with the model. Data were analysed using STATA™ (Version 8.0, Stata Corporation, College station, TX 77845, 800-782-8272).

Results

The scoliosis prevalence

The reported prevalence of AIS in the literature increases in the northern geographic latitudes and decreases as the latitude is approaching the equator (Table 1, Figure 1).
Table 1

Demonstrates data on AIS prevalence (%) according to the city or geographical periphery that the epidemiological study was performed, the size of the sample of the examined girls, the geographic latitude in degrees and the author and the year of publication.

City or Geographical Periphery

Geographic Latitude in degrees

No of girls screened

Prevalence of IS (%)

Author and year of publication

Helsinki (Finland)

65,00

401

12,0

Nissinen M et al 1993 [1]

Malmo (Sweden)

57,50

8469

3,21

Willner S & Uden A 1982 [2]

Esbjerg (Denmark)

55,30

1000

4,10

Laulund T et al 1982 [3]

Oxford (UK)

52,50

2613

3,20

Dickson RA et al 1983 [4]

Nottingham(UK)

52,00

321

1,90

Burwell RG et al 1983 [5]

Quebec (Canada)

47,50

14701

2,37

Morais Tet al 1985 [6]

Rochester (Minn, USA)

47,50

1212

2,70

Yawn BP et al 1999 [7]

Wisconsin (USA)

47,50

7462

2,03

Gore DR et al 1981 [8]

Slovenia

45,00

70200

2,89

Plenicar-Cucek M et al 1995 [9]

Montreal (Canada)

45,30

13500

2,70

Rogala EJ et al 1978 [10]

Cape Cod (USA)

42,00

928

5,00

Strayer LM et al, 1973 [11]

Delaware (USA)

38,50

25550

2,80

Shands AR et al 1955 [12]

Epirus (Greece)

38,00

40962

2,60

Soucacos PN et al 1997 [13]

California (USA)

36,00

1940

7,70

Brooks HL et al 1975 [14]

Crete (Greece)

35,00

10278

1,80

Koukourakis I et al 1997 [15]

Wakayaka (Japan)

34,00

1702

4,90

Sugita K 2000 [16]

Hu Guan (China)

25,30

12000

1,60

Ma X et al 1995 [17]

Changsha (China)

28,00

3963

2,45

Pin LH et al 1985 [18]

Taipei (Taiwan)

27,50

33596

1,00

Huang SC 1997 [19]

Singapoure

5,00

37141

0,93

Wong HK et al 2005 [20]

https://static-content.springer.com/image/art%3A10.1186%2F1748-7161-1-9/MediaObjects/13013_2006_Article_9_Fig1_HTML.jpg
Figure 1

Frequency weighted linear regression plot. The circle size represents the sample size of each study.

The final regression model is shown in Table 2. The inclusion of the quadratic term of latitude contributed to the explanatory power of the model according to partial F test and overall F test. According to the modelling of the data, a significant positive association between prevalence of IS and latitude was found (overall F p-value < 0.001), following a rather curvilinear trend (Figure 1).
Table 2

Linear regression results of AIS prevalence by the geographic latitude. The inclusion of the (Latitude)2 term implies a possible quadratic relationship.

Number of obs=

287939

R-squared=

0.509

 

F ( 2,288036)=

149257.39

Adj R-squared=

0.509

 

(Prob > F )

<0.001

Root MSE=

0.7122

 

Prevalence

Unstandardized coefficient (B)

P > t

95% Conf.

Interval

Latitude

0.024758

< 0.001

0.024045

0.0254713

Latitude^2

0.000484

<0.001

0.000472

0.0004965

Constant (Intercept)

0.712796

<0.001

0.703129

0.7224631

The age at menarch

Age at menarche shows a decreasing trend as the geographic latitude approaches approximately the 25–30 degrees and then increases again toward 0 degrees (near the equator) (Table 3, Figure 2a).
Table 3

Demonstrates the city or geographical periphery where each study was performed, the geographic latitude in degrees, the age at menarche in years, and the author and year of publication.

City or Geographical Periphery

Geographic Latitude in degrees

Age at menarche in years

Author and year of publication

Oslo (Norway)

59,93

16,00

Rosenberg 1991 [21]

Copenhagen (Denmark)

55,43

13,40

Helm P & Grolund L 1998 [22]

Rotterdam (Netherlands)

51,55

13,15

Mul et al 2001 [23]

Brussels (Belgium)

50,51

13,00

Vercauteren M & Susanne C 1984 [24]

Switzerland

47,00

13,40

Largo RH & Prader A 1983 [25]

Pecs (Hungary)

46,00

12,90

Dober I & Kiralyfalvi L 1993 [26]

Zagreb (Croatia)

45,48

13,13

Prebeg Z & Bralic I 2000 [27]

L' Aquila (Italy)

42,36

12,55

Danubio et al 2004 [28]

Madrid (Spain)

40,26

12,79

Marroban MD, Mesa MS 2000 [29]

Coimbra (Portugal)

40,15

12,53

Padez C & Rocha MA 2003 [30]

Dayton (Ohio, USA)

40,13

12,43

Chumlea et al 2003 [31]

Sardinia (Italy)

40,00

12,78

Floris G et al 1987 [32]

Athens (Greece)

38,00

12,58

Dacou-Voutetakis et al 1983 [33]

Thriasion Pedion, (Greece)

37,50

12,07

Grivas et al 2002 [34]

Columbia (USA)

38,53

13,20

Vadocz EA et al 2002 [35]

Atlanta (Georgia, USA)

33,46

12,60

Freedman et al 2002 [36]

Marrakech (Morocco)

31,49

13,04

Montero P et al 1999 [37]

Texas (USA)

31,14

13,10

Malina RM et al 1994 [38]

Chandigarh (India)

30,72

13,20

Sharma K 1990 [39]

Patiala (India)

30,35

12,54

Singh SP & Malhotra P 1988 [40]

Cairo (Egypt)

30,05

12,59

Attallah NL 1978 [41]

Shiraz (Iran)

29,38

12,84

Ayatollahi SM et al 2002 [42]

Zhejiang (China)

28,45

12,80

Hesketh T et al 2002 [43]

Hong Kong (China)

22,45

12,38

Huen KF et al 1997 [44]

Dominican Republic

19,00

13,10

Mancebo P et al 1990 [45]

Khartoum (Sudan)

15,55

13,35

Attallah NL et al 1983 [46]

Bangkok (Thailand)

13,73

12,35

Chompootaweep S et al 1997 [47]

Hausa (Nigeria)

12,24

13,50

Rehan N 1994 [48]

Carabobo (Venezuela)

10,23

12,86

Farid-Coupal N et al 1981 [49]

Nigeria

10,00

13,70

Oduntan SO et al 1976 [50]

Jaffna (Sri Lanka)

9,66

13,78

Prakash S & Pathmanathan G 1984 [51]

Kumasi (Ghana)

6,75

13,98

Adadevoh SW et al 1989 [52]

Yaunde (Cameroon)

3,85

13,98

Pasquet P et al 1999 [53]

https://static-content.springer.com/image/art%3A10.1186%2F1748-7161-1-9/MediaObjects/13013_2006_Article_9_Fig2_HTML.jpg
Figure 2

A. Illustration of the regression of age at menarche (in years) by latitude (in degrees) (p < 0.001). B. The linear correlation between age at menarche and geographic latitude is better shown in the figure where all observations below latitude of 25 degrees are not described.

The linear correlation between age at menarche and geographic latitude is better shown when all observations of lower latitude than 25 degrees are not described, (Figure 2b).

The age at menarche in healthy population regressed by latitude showed that there is a statistical significant correlation, (p < 0.001) (Table 4).
Table 4

Linear regression results of age at menarche by the geographic latitude.

Number of obs=

68763

R-squared=

0.342

 

F ( 2,288036)=

17855.41

Adj R-squared=

0.342

 

(Prob > F )

<0.001

Root MSE=

0.409

 

Age at menarche

Unstandardized coefficient (B)

P > t

95% Conf.

Interval

Latitude

-0.1123787

<0.001

-0.1135448

-0.1112126

Latitude^2

0.0018579

<0.001

0.0018381

0.0018776

Constant (Intercept)

14.07617

<0.001

14.06203

14.09031

Discussion

The regression curves of AIS prevalence and age at menarche by latitude are following a parallel decrement, especially in latitudes northern than 30°, as it is shown in figures 1 and 2 respectively.

The prevalence of AIS

On reviewing the literature, prevalence figures quoted by various authors, serve to emphasize an apparent divergence in different parts of the world. The figures may be reflecting differences in the definition of a scoliotic curve, the methods of clinical examination, the thresholds for referral, the age group screened and as to whether the studies are based on random sampling or a longitudinal survey of individual children over some years. On the other hand recorded figures may represent real environmental, geographical, genetic or racial influences [54].

In the present study the AIS prevalence decreases as the geographic latitude approaches the equator. The parallel decrement of their regression curves in northern hemisphere implicates the role of numerous factors related to latitude in the pathogenesis of AIS.

Geographic latitude and age at menarche

Although the age at menarche is to some extent influenced by family heredity, body weight, photic input and season, it seems more susceptible to modification by certain socioeconomic level and by specific disorders (such as diabetes, obesity and blindness) [55].

The influence of the geography should be distinguished between the effects of actual geographic factors (latitude, longitude, altitude, humidity and lighting) and those of the socioeconomic circumstances [55].

According to the critical weight hypothesis [56], there is a cut-off level for Body Mass Index (BMI) in relation to pubertal development. Beyond such degree of weight or BMI, there is no influence on age at menarche. The improved nutritional status among black girls in the recent years is implicated for an 8-month decrease of the median menarcheal age in black girls in a 20-year period, in contrast to a smaller decrease of 2 months in white girls at Bogalusa, a semi rural community near New Orleans, in the United States [36]. A stabilization of a previously decreasing trend of menarcheal age was recorded in studies from Norway [57] and from the Netherlands, [23] signifying the role of the nutritional status in sexual maturation.

Racial differences may also exist in other characteristics that have been suggested to influence pubertal development, such as the secretion of hormones by the hypothalamus, anterior pituitary, and ovary [58] or the social stress [59]. Recent studies on leptin, a protein which appears at higher levels among black girls [60] have suggested that it could act as a link between fat tissue and the central activation of the hypothalamus [61].

Earlier reports have not supported the belief once widely held, that sexual development occurs at an earlier age in the tropics than in temperate zones. It was reported that climate in itself has little or no effect on menarche [55, 62].

In countries with geographic latitude less than 30° there is different climate. In this region, the so called climatologically moderately favourable belt, the sunshine is estimated at 2 500 h/year [63].

In this area apart from the different climate, there is a low socioeconomic status that critically influences the anthropometric dimensions of adolescents. Poverty and children malnutrition results in delay of skeletal maturation. This delay reflects a situation in which the environmental conditions, in terms of nutrition, do not allow the child to reach the optimal genetic potential. Thus the reported age at menarche from those countries is rather confusing. Additionally, there are no reports on AIS prevalence from those countries. A possible association between age at menarche and AIS prevalence in geographic latitudes less than 30° is therefore not realistic.

Light and age at menarche

The effect of light on human biology is an issue that has rather not received much attention.

Environmental lighting exerts important effects on the age at which sexual maturation occurs in birds, [64, 65] and in monestrous mammals and polyestrous rodents [66].

A retinal response to environmental lighting mediates an expanding list of neuroendocrine effects, including control of pubescence, ovulation, and a large number of daily rhythms [67, 68].

The pattern of decrease of age at menarche with the shown specific trend as the geographic latitude approaches approximately down to 30 northern degrees could be attributed to daylight and cloudiness duration. The amount of sunlight and the quality of light (degrading relative irradiance and wavelength) may play a major role for the different initiation of menses in above-mentioned latitudes. It is useful for our study to cite the world distribution of solar radiation.

World distribution of solar radiation and quality of light [63]

Solar radiation is unevenly distributed throughout the world because of such variables as solar altitude, which is associated with latitude and season, and atmospheric conditions, which are determined by cloud coverage and degree of pollution. The reported guidelines for the broad identification of the geographic areas with favourable solar energy conditions in the Northern Hemisphere based on the collection of the direct component of sunlight are described below. Similar conditions apply for the Southern Hemisphere [69].

The most favourable belt is (15–35°N). It has over 3000 h/year of sunshine and limited cloud coverage. More than 90% of the incident solar radiation comes as direct radiation.

The moderately favourable belt (0–15°N), or equatorial belt, has high atmospheric humidity and cloudiness that tend to increase the proportion of the scattered radiation. The global solar intensity is almost uniform throughout the year as the seasonal variations are only slight. Sunshine is estimated at 2 500 h/year.

In the less favourable belt (35–45°N), the scattering of the solar radiation is significantly increased because of the higher latitudes and lower solar altitude. In addition, cloudiness and atmospheric pollution are important factors that tend to reduce sharply the solar radiation intensity. However, regions beyond 45°N have less favourable conditions for the use of direct solar radiation. This is because almost half of it is in the form of scattered radiation, which is more difficult to collect for use [63]. As it is also reported the ultraviolet irradiance is different in different latitudes, and a regression model of the form: lnE = a0 + a1cosΘ + a2Z, (where E is the seasonally integrated irradiance, Θ is the latitude and Z is the elevation of the observing site above sea level) explains 98.4% of the variance in the specific data sets of the related report [70]. The variation in human illumination exposure at different latitudes has also been elsewhere reported [71].

Moreover the different quality of light (wavelength) is probably responsible for the later age at menarche presented by girls living in higher altitudes, as it is reported in the available literature [39, 72], affecting probably the melatonin rhythm. This issue is in accordance with the reported increase in 6-Hydroxymelatonin excretion in humans during ascent to high altitudes [73]

Melatonin and age at menarche

At the onset of puberty, the hypothalamus, after being quiescent, resumes a marked pulsatile secretion of Gonadotrophine Releasing Hormone (GnRH), leading to an increased secretion of pituitary gonadotropines (Luteinizing Hormone [LH], and Follicle Stimulating Hormone [FSH]), especially during night, which in turn stimulates the gonadal functions. Cerebral adrenergic and/or dopamine neurotransmitters, endogenous opioids, and melatonin from the pineal gland are some of the neuroendocrine factors thought to be involved in the onset of puberty [74]

Melatonin is a hormone derived from the amino acid tryptophan and is secreted by the pineal gland. The enzyme Hydroxy-Indolo-O-Methyl-Transferase (HIOMT) converts the N-acetyl-serotonin to melatonin (Figure 3).
https://static-content.springer.com/image/art%3A10.1186%2F1748-7161-1-9/MediaObjects/13013_2006_Article_9_Fig3_HTML.jpg
Figure 3

Biosynthesis of melatonin.

Melatonin production is stimulated by darkness. The lack of light on the retina, through the optic nerve and the pre-ganglionic sympathetic fibres of the upper cervical ganglion of the sympathetic trunk reaches firstly the centre of vision and then through the post-ganglionic fibres reaches the pineal gland and provokes the release of norepinephrine from the end plates of the sympathetic system. Norepinephrine mediates the entrance of tryptophan into the pineal gland and controls the activity of many enzymes and mainly that of HIOMT, which is important for the synthesis of melatonin [75]. The pineal gland concentration of HIOMT reduces during day time and increases during night time. Thus the diurnal variation of melatonin is due to environmental light conditions. Consequently darkness leads to melatonin over production and light reduces the melatonin production [76, 77]. Melatonin is the main mediator that transfers the changes of the environmental light to the human cells [78].

Melatonin acts on the gonads indirectly, reducing the secretion of gonadotropines and mainly that of LH. This finding may explains the inhibition of ovulation in the Eskimos during the months of winter night period, and the increased rates of melatonin in normal women during night- time.

A controversy exists whether blind girls with no light stimuli experience delayed puberty. Zacharias and Wurtman in 1964 reported earlier age at menarche of girls suffering retroretineal fibroplasia than normal girls [77], while Thomas and Pizzarello in 1967 reported no difference [79] and Segos in 1995 reported that blind girls present late age at menarche [80] Jafarey et al in 1970 and 1971 reported that artificial lighting results in decreasing of age at menarche [81, 82]. A more thorough research is required in this issue.

Mean night time serum melatonin concentration presents an increased peak value at 1–3 yr of age (329.5 ± 42.0 pg/mL), and lessens thereafter, averaging 62.5 ± 9.0 pg/mL in individuals aged 15–20 yr and 29.2 ± 6.1 pg/mL in old age (70–90 yr) [83] The decrease in nocturnal serum melatonin in children and adolescents correlated with body weight and body surface area, whereas no such correlation was found at a later age [83].

There are numerous limitations to interpret studies of melatonin in human subjects because of methodological considerations, such as the use of single blood samples collected during the day or the night, failure to include age related characteristics of melatonin secretion, lack of control of the actual duration and intensity of light exposure, and use of broad clinical features without hormonal markers to define puberty [84].

Sexual maturation can be delayed in experimental animals by exogenous melatonin administration or by short day exposure [85, 88]. A rapid decrease in melatonin has also been observed during successful treatment of patients with delayed puberty [85].

AIS and age at menarche

In this study, two linear regression procedures conducted, one between the prevalence of idiopathic scoliosis and the geographic latitude, and the other between the age at menarche and the geographic latitude. The reader could ask the reasonable question why a direct correlation between the prevalence of idiopathic scoliosis and the age at menarche was not performed? The answer is that due to the study design, the data were collected from two different groups of publications, the first consisting of publications regarding the prevalence of scoliosis whereas the second describing the different age at menarche in various geographic latitudes. As a result, the statistical analysis was done with two different samples. Since the data for the prevalence of IS and the age at menarche referred to different latitudes, a direct correlation could not be carried out. Moreover, no articles which had data for age at menarche and the prevalence of IS for a specific latitude could be found. At long last the results of this study suggest a possible correlation between age at menarche and prevalence of IS based on statistical analysis.

AIS is associated with pubertal growth spurt and its progression decelerates after completion of skeletal maturity. The age at onset of menarche is indicative of the remaining growth potential of girls. Late onset of menses correlates with delayed skeletal maturity and it implies that there is a potential for progression of a scoliotic curve. In a scoliotic girl, it is very important to predict the evolution of the curve and to advise accordingly the patient and her family. Goldberg et al [86, 87] have shown that menarcheal status is a more meaningful predictor of curve stability than Risser sign, because at menarche peak growth velocity is already past [88] and although Risser stage 1 is still, on average, 8 months away [89, 90], the possibility for more growth and significant progression, especially for smaller curves is declining rapidly. Furthermore, girls who are pre-menarcheal at diagnosis have a higher prevalence of surgery, as the menarcheal status alone will divide a female patient group into those who are at significant risk of surgery and those who are not [91]. A clear association exists between the deterioration of a scoliotic curve and periods of rapid growth, such those occurring before pubarche.

Melatonin and AIS

The role of melatonin deficiency in AIS pathogenesis has been proposed by Machida et al [92] who produced scoliosis similar to those of human adolescent idiopathic scoliosis in pinealectomized chickens. When pinealectomized chickens were administered melatonin, the scoliosis was prevented. They proposed that a defect in melatonin production might be related to the aetiology of human idiopathic scoliosis.

There is a controversy whether lower animal models are appropriate for studying scoliosis. Chickens present extrapineal sites of melatonin production [93, 94] that contribute to circulating melatonin levels, in contrast to humans that no extrapineal sources affect the circadian rhythm of melatonin [95]. There is a loss of the nighttime melatonin peak and a drop in basal levels below detection after pinealectomy in humans [96, 97], whereas in chickens secretion is preserved with elimination of the nighttime peak [98]. Melatonin's actions appear to differ between humans, other mammals, and other vertebrates [93, 9597, 99]. In humans melatonin may act by modulating calcium-activated calmodulin [100].

In a prospective study on pinealectomy in bipedal nonhuman primates, Cheung et al reported that none of the 18 monkeys developed scoliosis in a mean follow up period of 28 months. This study strongly suggests that the possible etiologic factors producing idiopathic scoliosis in lower animals are different from primates, and findings in lower animals cannot necessarily be extrapolated to human beings [101].

Studies on melatonin circadian secretion in humans report contradictory results. Machida et al reported that the integrated melatonin concentration throughout the 24-hour period in the patients who had a progressive curve was significantly lower than the level in the patients who had a stable curve or in the control group [102].

Hilibrand et al in a study that was conducted to test the suggestion of Machida found, in contrary to their research hypothesis, that morning urine melatonin levels were higher in patients with scoliosis than in the control subjects, but the differences between these values were not statistically significant [103]. They also reported a non-statistically significant difference of morning urine melatonin levels between patients with progressive and stable curves. The authors concluded that there was no difference in melatonin levels, as reflected in morning and evening urine collections, between patients with AIS and control subjects.

Fegan et al, in a case-control study of 24-hour urinary melatonin production in patients with adolescent idiopathic scoliosis reported that in adolescent idiopathic scoliosis, neither the presentation with a stable spinal deformity, nor presentation with a severe deformity requiring surgery is associated with melatonin deficiency [104].

No difference was also found by Bagnall et al in single day- and night-time measurements of the serum melatonin level in a control group and 7 patients with progressive adolescent idiopathic scoliosis [105]. In addition, no difference was found by Brodner et al in the urinary excretion of 6-sufatoxyl-melatonin in a control group and patients with progressive adolescent idiopathic scoliosis [106].

The argument against the alleged role of melatonin deficiency in AIS pathogenesis is contained in reports highlighting that an increased incidence of scoliosis has not been observed in children after pinealectomy or pineal irradiation because of pineal neoplasias, although they have a lack of serum melatonin [107109].

Geographic latitude, lifestyle differences and scoliosis

The different prevalence of IS by latitude could be probably attributed also to different lifestyle of people at deferent geographical latitudes. The seating people in the northern hemisphere societies are reducing their lumbar lordosis contrary to the physiologic sagittal profile exhibited in photographs of the African people of the tribe Nuba, as seen in the book of German photographer Leni Riefenstahl. Reduced lumbar lordosis (the seating effect in the northern hemisphere societies) frequently occurs in correlation with the lateral spinal curvature. Loss of lumbar lordosis seems to be a fundamental problem leading to a destabilization of the spine also in frontal and coronal plane and vice versa correction of lumbar lordosis seems to correct spinal deformities also in fontal and coronal plane [110]. This mechanistic approach to scoliotic deformity prevalence which is quite different to the biological approach discussed in this study probably needs to be addressed with pertinent research in human groups living in different latitudes, which is lacking so far from the available literature.

A hypothesis

It has been assumed that there are two types of pathogenetic factors for AIS, the initiating and those that cause progression. Initiating factors that can meaningfully be distinguished from progressing factors would eventually faint or disappear, while progressive factors, which are generally thought to be a mechanical process, are associating with curve magnitude [111].

A possible preservation of high levels of melatonin secretion during the pre-menarcheal period in scoliotic girls due to light insufficiency in northern countries is associated with delay of the age at menarche. These high levels of melatonin are possibly identifiable before presentation of AIS, but would not be apparent at the time of clinical presentation of AIS in the vast majority of cases. The pre-menarcheal elevated levels of melatonin could be considered as a possible initiating factor of idiopathic scoliosis and it does not correlate with the severity and the site of the curve. It alters growth by lengthening the period of spine vulnerability while other pre-existing or aetiological factors are contributing to the development of AIS. Longitudinal studies on melatonin secretion in pre-pubertal girls that are at risk to develop AIS (i.e. with trunk asymmetry but no radiographic evidence of AIS) could be undertaken in order to test this hypothesis.

The clinical relevance and therapeutic implication that could also be derived from this study is that in northern latitudes, in girls with anticipated progressive scoliosis with no menarche, hormonal treatment in order to commence it might be of potential value to stop progression.

Conclusion

In this survey it appears that late age at menarche is parallel with higher prevalence of AIS, especially in latitudes northern than 30 degrees. Pubarche appears later in girls that live in northern latitudes and thus prolongs the period of spine vulnerability while other pre-existing or aetiological factors are contributing to the development of AIS.

Abbreviations

(AIS): 

Adolescent Idiopathic Scoliosis

(HIOMT): 

Hydroxy-Indolo-O-Methyl-Transferase

(GnRH): 

Gonadotrophine Releasing Hormone

(LH): 

Luteinizing Hormone

(FSH): 

Follicle Stimulating Hormone

Declarations

Acknowledgements

The authors would like to express their thanks to Prof. RG Burwell for critical comments on the study, Prof. M Asher for critical comments on the study, Mrs. Christina Maziotou for her involvement in the "Thriasio" school-screening programme and for the collection and data entry of the school-screening related information and Miss Akrivi Arvaniti for her involvement in the "Thriasio" school-screening programme.

Authors’ Affiliations

(1)
Orthopaedic Department, "Thriasio" General Hospital

References

  1. Nissinen M, Heliovaara M, Ylikoski M, Poussa M: Trunk asymmetry and screening for scoliosis: a longitudinal cohort study of pubertal schoolchildren. Acta Paediatr. 1993, 82 (1): 77-82.PubMed
  2. Willner S, Uden A: A prospective prevalence study of scoliosis in Southern Sweden. Acta Orthop Scand. 1982, 53 (2): 233-7.PubMed
  3. Laulund T, Sojbjerg JO, Horlyck E: Moire topography in school screening for structural scoliosis. Acta Orthop Scand. 1982, 53 (5): 765-8.PubMed
  4. Dickson RA: Scoliosis in the community. Br Med J. 1983, 19 (6365): 615-8. 286
  5. Burwell RG, James NJ, Johnson F, Webb JK, Wilson YG: Standardised trunk asymmetry scores. A study of back contour in healthy school children. J Bone Joint Surg Br. 1983, 65 (4): 452-63.PubMed
  6. Morais T, Bernier M, Turcotte F: Age- and sex-specific prevalence of scoliosis and the value of school screening programs. Am J Public Health. 1985, 75 (12): 1377-80.PubMedPubMed Central
  7. Yawn BP, Yawn RA, Hodge D, Kurland M, Shaughnessy WJ, Ilstrup D, Jacobsen SJ: A population-based study of school scoliosis screening. JAMA. 1999, 282 (15): 1472-4. 10.1001/jama.282.15.1427.
  8. Gore DR, Passehl R, Sepic S, Dalton A: Scoliosis screening: results of a community project. Pediatrics. 1981, 67 (2): 196-200.PubMed
  9. Cucek-Plenicar M: 3-D Etiological and prognostic aspects. Screening for scoliosis in Slovenia: Results of 15 years. Three-dimensional Analysis of Spinal Deformities. Edited by: D'Amico M, Merolli A, Santambrogio GC. 1995, Amsterdam, Netherlands: IOS Press, 275-277.
  10. Rogala EJ, Drummond DS, Gurr J: Scoliosis: incidence and natural history. A prospective epidemiological study. J Bone Joint Surg Am. 1978, 60 (2): 173-6.PubMed
  11. Strayer LM: The incidence of scoliosis in post-partum female on Cape Cod. J Bone Joint Surg Am. 1973, 55A: 436-
  12. Shands AR, Eisberg HB: The incidence of scoliosis in the state of Delaware; a study of 50,000 minifilms of the chest made during a survey for tuberculosis. J Bone Joint Surg Am. 1955, 37A (6): 1243-9.
  13. Soucacos PN, Soucacos PK, Zacharis KC, Beris AE, Xenakis TA: School-screening for scoliosis. A prospective epidemiological study in northwestern and central Greece. J Bone Joint Surg Am. 1997, 79 (10): 1498-503.PubMed
  14. Brooks HL, Azen SP, Gerberg E, Brooks R, Chan L: Scoliosis: A prospective epidemiological study. J Bone Joint Surg Am. 1975, 57 (7): 968-72.PubMed
  15. Koukourakis I, Giaourakis G, Kouvidis G, Kivernitakis E, Blazos J, Koukourakis M: Screening school children for scoliosis on the island of Crete. J Spinal Disord. 1997, 10 (6): 527-31.PubMed
  16. Sugita K: Epidemiological study on idiopathic scoliosis in high school students. Prevalence and relation to physique, physical strength and motor ability. Nippon Koshu Eisei Zasshi. 2000, 47 (4): 320-5.PubMed
  17. Ma X, Zhao B, Lin QK: Investigation on scoliosis prevalence among 24,130 school children. Zhonghua Liu Xing Bing Xue Za Zhi. 1995, 16 (2): 109-10.PubMed
  18. Pin LH, Mo LY, Lin L, Hua KL, Hui CHP, Hui SD, Chang BD, Chang YY: Early diagnosis of scoliosis based on school-screening. J Bone Joint Surg Am. 1985, 67 (8): 1202-5.PubMed
  19. Huang SC: Cut-off point of the Scoliometer in school scoliosis screening. Spine. 1997, 22 (17): 1985-9. 10.1097/00007632-199709010-00007.PubMed
  20. Wong HK, Hui JH, Rajan U, Chia HP: Idiopathic scoliosis in Singapore schoolchildren: a prevalence study 15 years into the screening program. Spine. 2005, 30 (10): 1188-96. 10.1097/01.brs.0000162280.95076.bb.PubMed
  21. Rosenberg M: Menarheal age for Norwegian women born 1830–1960. Ann Hum Biol. 1991, 18 (3): 207-19. 10.1080/03014469100001532.PubMed
  22. Helm P, Grolund L: A halt in the secular trend towards earlier menarche in Denmark. Acta Obstet Gynecol Scand. 1998, 77 (2): 198-200. 10.1034/j.1600-0412.1998.770213.x.PubMed
  23. Mul D, Fredriks AM, Van Buuren S, Oostdijk W, Verloove-Vanhorick SP, Wit JM: Pubertal development in The Netherlands 1965–1997. Pediatr Res. 2001, 50 (4): 479-86.PubMed
  24. Vercauteren M, Susanne C: Current age at menarche in Belgium. Anthropol Anz. 1984, 42 (3): 211-7.PubMed
  25. Largo RH, Prader A: Pubertal development in Swiss girls. Helv Paediatr Acta. 1983, 38 (3): 229-43.PubMed
  26. Dober I, Kiralyfalvi L: Pubertal development in south-Hungarian boys and girls. Ann Hum Biol. 1993, 20 (1): 71-4. 10.1080/03014469300002512.PubMed
  27. Prebeg Z, Bralic I: Changes in menarcheal age in girls exposed to war conditions. Am J Hum Biol. 2000, 12 (4): 503-508. 10.1002/1520-6300(200007/08)12:4<503::AID-AJHB10>3.0.CO;2-H.PubMed
  28. Danubio ME, De Simone M, Vecchi F, Amicone E, Altobelli E, Gruppioni G: Age at menarche and age of onset of pubertal characteristics in 6–14 years old girls from the Province of L'Aquila. Am J Hum Biol. 2004, 16 (4): 470-8. 10.1002/ajhb.20028.PubMed
  29. Marrodan MD, Mesa MS, Arechiga J, Perez-Magdaleno A: Trend in menarcheal age in Spain. Ann Hum Biol. 2000, 27 (3): 313-9. 10.1080/030144600282190.PubMed
  30. Padez C, Rocha MA: Age at menarche in Coimbra (Portugal) school girls. Ann Hum Biol. 2003, 30 (5): 622-32. 10.1080/03014460310001592650.PubMed
  31. Chumlea WC, Schubert CM, Roche AF, Kulin HE, Lee PA, Himes JH, Sun SS: Age at menarche and Racial Comparisons in US girls. Pediatrics. 2003, 111 (1): 110-113. 10.1542/peds.111.1.110.PubMed
  32. Floris G, Murgia E, Sanciu GM, Sanna E: Age at menarche in Sardinia (Italy). Ann Hum Biol. 1987, 14 (3): 285-6. 10.1080/03014468700009051.PubMed
  33. Dacou-Vouletakis C, Klontza D, Lagos P, Tzonou A, Katsarou E, Antoniadis S, Papazisis G, Papadopoulos G, Matsaniotis N: Age of pubertal stages including menarche in Greek girls. Ann Hum Biol. 1983, 10 (6): 557-63. 10.1080/03014468300006781.
  34. Grivas TB, Samelis P, Pappa AS, Stavlas P, Polyzois D: Menarche in scoliotic and nonscoliotic Mediterranean girls. Is there any relation between menarche and laterality of scoliotic curves?. Stud Health Technol Inform. 2002, 88: 30-6.PubMed
  35. Vadocz EA, Siegel SR, Malina RM: Age at menarche in competitive figure skaters: variation by competency and discipline. J Sports Sci. 2002, 20 (2): 93-100. 10.1080/026404102317200800.PubMed
  36. Freedman DS, Khan LK, Serdula MK, Dietz WH, Srinivasan SR, Berenson GS: Relation of age at menarche to race, time period, and anthropometric dimensions: the Bogalusa Heart Study. Pediatrics. 2002, 110 (4): 43-10.1542/peds.110.4.e43.
  37. Montero P, Bernis C, Loukid M, Hilali K, Baali A: Characteristics of menstrual cycles in Moroccan girls: prevalence of dysfunctions and associated behaviours. Ann Hum Biol. 1999, 26 (3): 243-9. 10.1080/030144699282741.PubMed
  38. Malina RM, Ryan RC, Bonci CM: Age at menarche in athletes and their mothers and sisters. Ann Hum Biol. 1994, 21 (5): 417-22. 10.1080/03014469400003432.PubMed
  39. Sharma K: Age at menarche in northwest Indian females and a review of Indian data. Ann Hum Biol. 1990, 17 (2): 159-62. 10.1080/03014469000000912.PubMed
  40. Singh SP, Malhotra P: Secular shift in menarcheal age of Patiala (India) schoolgirls between 1974 and 1986. Ann Hum Biol. 1988, 15 (1): 77-80. 10.1080/03014468800009481.PubMed
  41. Attallah NL: Age at menarche of schoolgirls in Egypt. Ann Hum Biol. 1978, 5 (2): 185-9. 10.1080/03014467800002781.PubMed
  42. Ayatollahi SM, Dowlatabadi E, Ayatollahi SA: Age at menarche in Iran. Ann Hum Biol. 2002, 29 (4): 355-62. 10.1080/03014460110086817.PubMed
  43. Hesketh T, Ding QJ, Tomkins A: Growth status and menarche in urban and rural China. Ann Hum Biol. 2002, 29 (3): 348-52. 10.1080/03014460110079455.PubMed
  44. Huen KF, Leung SS, Lau JT, Cheung AY, Leung NK, Chiu MC: Secular trend in the sexual maturation of southern Chinese girls. Acta Paediatr. 1997, 86 (10): 1121-4.PubMed
  45. Mancebo P, Contreras C, Perez E, Molina E, Contreras A, Morla E: Age at menarche of Dominican girls. Arch Domin Pediatr. 1990, 26 (1): 7-11.PubMed
  46. Attallah NL, Matta WM, El-Mankoushi M: Age at menarche of schoolgirls in Khartoum. Ann Hum Biol. 1983, 10 (2): 185-8. 10.1080/03014468300006321.PubMed
  47. Chompootaweep S, Tankeyoon M, Poomsuwan P, Yamarat K, Dusitsin N: Age at menarche in Thai girls. Ann Hum Biol. 1997, 24 (5): 427-33. 10.1080/03014469700005192.PubMed
  48. Rehan N: Characteristics of the menarche in Hausa girls in Nigeria. J Obstet Gynaecol. 1994, 14 (4): 265-8.
  49. Farid-Coupal N, Contreras ML, Castellano HM: The age at menarche in Carabobo, Venezuela with a note on secular trend. Ann Hum Biol. 1981, 8 (3): 283-8. 10.1080/03014468100005051.PubMed
  50. Oduntan SO, Ayeni O, Kale OO: The age of menarche in Nigerian girls. Ann Hum Biol. 1976, 3 (3): 269-74. 10.1080/03014467600001431.PubMed
  51. Prakash S, Pathmanathan G: Age at menarche in Sri Lankan Tamil girls in Jaffna. Ann Hum Biol. 1984, 11 (5): 463-6. 10.1080/03014468400007361.PubMed
  52. Adadevoh SW, Agble TK, Hobbs C, Elkins TE: Menarcheal age in Ghanaian school girls. Int J Gynaecol Obstet. 1989, 30 (1): 63-8. 10.1016/0020-7292(89)90217-8.PubMed
  53. Pasquet P, Biyong AM, Rikong-Adie H, Befidi-Mengue R, Garba MT, Froment A: Age at menarche and urbanization in Cameroon: current status and secular trends. Ann Hum Biol. 1999, 26 (1): 89-97. 10.1080/030144699283001.PubMed
  54. Goldberg CJ, Dowling FE, Fogarty EE: Adolescent idiopathic scoliosis- early menarche, normal growth. Spine. 1993, 18 (5): 529-535.PubMed
  55. Zacharias L, Wurtman RJ: Age at menarche Genetic and Enviromental influences. New England J Medicine. 1969, 280: 868-875.
  56. Frisch RE, Revelle R: Height and weight at menarche and a hypothesis of critical body weights and adolescent events. Science. 1970, 169: 397-399.PubMed
  57. Liestol K, Rosenberg M: Height, weight and menarcheal age of schoolgirls in Oslo-an update. Ann Hum Biol. 1995, 22: 199-205. 10.1080/03014469500003862.PubMed
  58. Apter D: Development of the hypothalamic-pituitary-ovarian axis. Ann N Y Acad Sci. 1997, 816: 9-21.PubMed
  59. Wierson M, Long PJ, Forehand RL: Toward a new understanding of early menarche: the role of environmental stress in pubertal timing. Adolescence. 1993, 28: 913-924.PubMed
  60. Wong WW, Nicolson M, Stuff JE, Butte NF, Ellis KJ, Hergenroeder AC, Hill RB, Smith EO: Serum leptin concentrations in Caucasian and African-American girls. J Clin Endocrinol Metab. 1998, 83: 3574-3577. 10.1210/jc.83.10.3574.PubMed
  61. Flier JS: What's in a name? In search of leptin's physiologic role. J Clin Endocrinol Metab. 1998, 83: 1407-1413. 10.1210/jc.83.5.1407.PubMed
  62. Kennedy W: Menarche and menstrual type: notes on 10.000 case records. J Obst & Gynaec Brit Emp. 1933, 40: 792-804.
  63. Acra A, Judi M, Mu'allem H, Karahagopian Y, Raffoul Z: Water Disinfection by Solar Radiation. Assessment and Application. 1990, Ottawa, Ont., Canada: International Development Research Centre
  64. Rowan W: Relation of light to bird migration and developmental changes. Nature. 1925, 115: 494-
  65. Wurtman RJ: Effects of light and visual stimuli on endocrine function. Neuro-endocrinology. Edited by: Martini L, Ganong WF. 1967, New York: Academic Press, 2: 20-
  66. Fiske VM: Effect of light on sexual maturation, estrous cycles, and anterior pituitary of the rat. Endocrinology. 1941, 29: 187-
  67. Wurtman RJ, Neer RN: Good light and bad. New England J Medicine. 1970, 282 (7): 394-395.
  68. Wurtman RJ: The effects of light on the human body. Sci Am. 1975, 233 (1): 69-77.PubMed
  69. Acra A, Raffoul Z, Karahagopian Y: Solar disinfection of drinking water and oral rehydration solutions. 1984, United Nations Children's Fund, Amman, Jordan, 56-
  70. Frederick JE, Slusser JR, Bigelow DS: Annual and interannual behavior of solar ultraviolet irradiance revealed by broadband measurements. Photochemistry and Photobiology. 2000, 72 (4): 488-496. 10.1562/0031-8655(2000)072<0488:AAIBOS>2.0.CO;2.PubMed
  71. Cole RJ, Kripke DF, Wisbey J, Mason WJ, Gruen W, Hauri PJ, Juarez S: Variation in human illumination exposure at different latitudes. J Biol Rhythms. 1995, 10 (4): 324-34.PubMed
  72. Valsik JA, Stukovsky R, Bernatova L: Geographic and social factors that affect the age of puberty. Biotypologie. 1963, 24 (3): 109-23.PubMed
  73. Frisch H, Waldhauser F, Waldhor T, Mullner-Eidenbock A, Neupane P, Schweitzer K: Increase in 6-hydroxymelatonin excretion in humans during ascent to high altitudes. The Journal of Clinical Endocrinology & Metabolism. 2004, 89 (9): 4388-90. 10.1210/jc.2003-032214.
  74. Sizonenko PC: Physiology of puberty. J Endocrinol Invest. 1989, 12 (Suppl): 59-63.PubMed
  75. Batrinos ML: Endocrinology. 1995, Athens, Greece: P.Paschalidis Medical Puplications
  76. Aravantinos D: Physiology of the woman. 1985, Athens, Greece: Parizianos Publications
  77. Zacharias L, Wurtman RJ: Blindness: its relation to age at menarche. Science. 1964, 144: 1154-PubMed
  78. Irmak MK, Topal T, Oter S: Melatonin seems to be a mediator that transfers the environmental stimuli to oocytes for inheritance of adaptive changes through epigenetic inheritance system. Med Hypotheses. 2005, 64 (6): 1138-43. 10.1016/j.mehy.2004.12.014.PubMed
  79. Thomas JB, Pizzarello DJ: Blindness, biologic rhythms, and menarche. Obstet Gynecol. 1967, 30 (4): 507-9.PubMed
  80. Segos C: Puberty. Honorary volume for Professor DJ Aravantinos. Edited by: Michalas SP, Goumalatsios NG. 1999, Athens, Greece : Parisianos Publications, 629-633.
  81. Jafarey NA, Khan MY, Jafarey SN: Role of artificial lighting in decreasing the age of menarche. Lancet. 1970, 29 (7670): 471-10.1016/S0140-6736(70)90092-9. 2
  82. Jafarey NA, Khan MY, Jafarey SN: Effect of artificial lighting on the age of menarche. Lancet. 1971, 3:1 (7701): 707-10.1016/S0140-6736(71)92729-2.
  83. Waldhauser F, Weiszenbacher G, Tatzer E, Gisinger B, Waldhauser M, Schemper M, Frisch H: Alterations in nocturnal serum melatonin levels in humans with growth and aging. J Clin Endocrinol Metab. 1988, 66: 648-652.PubMed
  84. Cavallo A: Melatonin and human puberty: current perspectives. J Pineal Res. 1993, 15: 115-121.PubMed
  85. Arendt J, Labib MH, Bojkowski C, Hanson S, Marks V: Rapid decrease in melatonin production during successful treatment of delayed puberty (letter). Lancet. 1989, 1: 1326-10.1016/S0140-6736(89)92716-5.PubMed
  86. Goldberg CJ, Dowling FE, Fogarty EE: Adolescent idiopathic scoliosis: is rising growth rate the triggering factor in progression?. Eur Spine J. 1993, 2: 29-36. 10.1007/BF00301052.PubMed
  87. Owen R, Taylor JF, McKendrick O, Dangerfield P: Current incidence of scoliosis in schoolchildren in the city of Liverpool. Scoliosis 1979 – Based on the proceedings of the sixth symposium on scoliosis held at the Cardiothoracic Institute Brompton Hospital London on 17th and 18th September 1979. Edited by: Zorab PA, Siegler D. 1980, London: Academic Press, 31-34.
  88. Utiger RD: Melatonin: The hormone of darkness. New Eng J Med. 1992, 1377-9.
  89. Scoles PV, Salvagno R, Villalba K, Riew D: Relationship of iliac crest maturation to skeletal and chronological age. J Paediatric Orthop. 1988, 8: 639-644.
  90. Terver S, Kleinman R, Bleck EE: Growth landmarks and the evolution of scoliosis: a review of pertinent studies and their usefulness. Dev Med & Child Neurol. 1980, 22: 675-684.
  91. Goldberg CJ, Moore DP, Fogarty EE, Dowling FE: Adolescent Idiopathic Scoliosis: the effect of brace treatment on the prevalence of surgery. Spine. 2001, 26 (1): 42-7. 10.1097/00007632-200101010-00009.PubMed
  92. Machida M, Dubousset J, Imamira Y, Iwaya T, Yamada T, Kimura J: An experimental study in chickens for the pathogenesis of idiopathic scoliosis. Spine. 1993, 18: 1609-13.PubMed
  93. Huether G: Melatonin synthesis in the GI tract and the impact of nutrition factors on circulating melatonin. Ann NY Acad Sci. 1994, 719: 146-58.PubMed
  94. Reiter RJ: The melatonin rhythm: Both a clock and a calendar. Experientia. 1993, 49: 654-64. 10.1007/BF01923947.PubMed
  95. Minneman KP, Wurtman RJ: The pharmacology of the pineal gland. Annu Rev Pharmacol Toxicol. 1976, 16: 33-51. 10.1146/annurev.pa.16.040176.000341.PubMed
  96. Cavallo A: The pineal gland in human beings: Relevance to pediatrics. J Pediatr. 1993, 123: 843-51. 10.1016/S0022-3476(05)80377-4.PubMed
  97. Huether G: The contribution of extrapineal sites of melatonin synthesis to circulating melatonin levels in higher vertebrates. Experientia. 1993, 49: 665-70. 10.1007/BF01923948.PubMed
  98. Cogburn LA, Wilson-Placentra S, Letcher LR: Influence of pinealectomy on plasma and extrapineal melatonin rhythms in young chickens. Gen Comp Endocrinol. 1987, 68: 343-56. 10.1016/0016-6480(87)90073-6.PubMed
  99. Krause DN, Dubocovich ML: Regulatory sites in the melatonin system of mammals. Trends Neurosci. 1990, 13: 464-70. 10.1016/0166-2236(90)90100-O.PubMed
  100. Lowe TG: Skeletal muscle and platelet abnormalities in adolescent idiopathic scoliosis. Etiology of adolescent idiopathic scoliosis: Current trends and relevance to new treatment approaches. Edited by: Burwell RG, Dangerfield PH, Lowe TG, Margulies JY. 2000, State of the Art Reviews: Spine, 14 (2): 441-6.
  101. Cheung KM, Wang T, Poon AM, Carl A, Tranmer B, Hu Y, Luk KD, Leong JC: The effect of pinealectomy on scoliosis development in young nonhuman primates. Spine. 2005, 30 (18): 2009-13. 10.1097/01.brs.0000179087.38730.5d.PubMed
  102. Machida M, Dubousset J, Imamura Y, Miyashita Y, Yamada T, Kimura J: Melatonin: A possible role in pathogenesis of adolescent idiopathic scoliosis. Spine. 1996, 21 (10): 1147-1152. 10.1097/00007632-199605150-00005.PubMed
  103. Hilibrand AS, Blakemore LC, Loder RT, Greenfield ML, Farley FA, Hensinger RN, Hariharan M: The role of melatonin in the pathogenesis of adolescent idiopathic scoliosis. Spine. 1996, 21 (10): 1140-1146. 10.1097/00007632-199605150-00004.PubMed
  104. Fagan AB, Kennaway DJ, Sutherland AD: Total 24-hour melatonin secretion in adolescent idiopathic scoliosis: A case-control study. Spine. 1998, 23 (1): 41-46. 10.1097/00007632-199801010-00009.PubMed
  105. Bagnall KM, Raso VJ, Hill DL, Moreau M, Mahood JK, Jiang H, Russell G, Bering M, Buzzell GR: Melatonin levels in idiopathic scoliosis : Diurnal and nocturnal serum melatonin levels in girls with adolescent idiopathic scoliosis. Spine. 1996, 21,: 1974-1978. 10.1097/00007632-199609010-00006.
  106. Brodner W, Krepler P, Nicolakis M, Brodner W, Krepler P, Nicolakis M, Langer M, Kaider A, Lack W, Waldhauser F: Melatonin and adolescent idiopathic scoliosis. J Bone Joint Surg [Br]. 2002, 82: 399-403. 10.1302/0301-620X.82B3.10208.
  107. Etzioni A, Luboshitzky R, Tiosano D, Ben-Harush M, Goldsher D, Lavie P: Melatonin replacement corrects sleep disturbances in a child with pineal tumor. Neurology. 1996, 46: 261-263.PubMed
  108. Murata J, Sawamura Y, Ikeda J, Hashimoto S, Honma K: Twenty four hour rhythm of melatonin in patients with a history of pineal and or hypothalamo-neurohypophyseal germinoma. J Pineal Res. 1998, 25: 159-166.PubMed
  109. Vorkapic P, Waldhauser F, Bruckner R, Biegelmayer C, Schmidbauer M, Pendl G: Serum melatonin levels : a new neurodiagnostic tool in pineal region tumors?. Neurosurgery. 1987, 21: 817-824.PubMed
  110. Weiss HR, Dallmayer R, Gallo D: Sagittal counter forces (SCF) in the treatment of idiopathic scoliosis : a preliminary report. Pediatr Rehabil. 2006, 9 (1): 24-30. 10.1080/13638490500038126.PubMed
  111. Burwell RG: Aetiology of idiopathic scoliosis: current concepts. Pediatr Rehabil. 2003, 6 (3–4): 137-70.PubMed

Copyright

© Grivas et al; licensee BioMed Central Ltd. 2006

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Advertisement