Pubertal Stage-Dependent Anthropometric Variations in Turkish Children with Adolescent Idiopathic Scoliosis: An In-Depth Analysis

Background

Adolescent idiopathic scoliosis (AIS) represents a complex 3-dimensional structural disorder affecting the spine. It appears in children, predominantly between the age of 10 years and the end of their skeletal maturity [1]. A myriad of factors, including genetic, intrinsic, and environmental elements, play a critical role in the onset and progression of AIS. Notably, researchers have suggested a connection between growth and development in children, hormone release, posture, and physical activity [2,3].

Historically, different prognostic indices and regression equations have been proposed to understand and predict the progression of AIS. One such approach was proposed by Lonstein and Carlson [4], focusing on 3 factors: the initial Cobb angle, which reflects the degree of scoliosis; the Risser degree, an indicator of skeletal maturity; and chronological age. Further advancement in this field saw Peterson and Nachemson [5] introducing a 4-factor regression equation [6]. However, many subsequent studies still need to fully consider Tanner’s staging, a measure of physical development, leading to a primary reliance on changes in the Cobb angle to define curve progression [7,8].

Realizing that an increase in the Cobb angle may not have direct clinical implications, a need emerged to refine these predictive factors, encompassing elements such as age at onset, menarchal status, and the Cobb angle itself [9]. This need was underscored by evidence suggesting a strong correlation between AIS progression and growth spurts during puberty [10–15]. Thus, a more nuanced understanding of pubertal growth patterns in AIS patients, in terms of both sexes, is crucial.

Peak height velocity predicts residual growth more accurately than do Risser sign or chronological age [16]. Recognizing puberty onset and measuring its progression in boys can be challenging. For instance, boys lack physiological events such as menarche, which marks specific stages of puberty in girls. Nevertheless, elements like secondary sex characteristics and changes in bone age and testicular volume can provide practical markers to establish correlations between somatic signs of puberty and its stages [17].

The criterion for the onset of puberty in boys is the testicular volume. In boys, the increase in testicular volume begins at a mean age of 12 years (range, 9.5–13.5 years) [18,19]. This process lasts an average of 3.5 years [20]. Since the average age at the onset of puberty and duration of puberty [21] in boys and the average age at the onset of puberty and duration of puberty in girls in Turkish society differ [22], the growth spurt in boys occurs 2 years later than in girls and continues until the age of 18 [23]. A boy has reached 99% of his adult height at a bone age of 17 years [24]. In girls, height growth decreases after menarche and the average height gain is 7 cm per year. A girl reaches 99% of her adult height at a bone age of 15 years [20].

Height measured during physical examination and the annual growth rate calculated for a child at follow-up are the most important criteria used to evaluate growth. The calculated values are measured against national reference values to determine the child’s growth status [25].

Given the notable differences in growth histories between boys and girls with AIS, we hypothesize that boys with AIS exhibit abnormal growth patterns during puberty, distinct from those observed in girls with AIS. Although the progression of AIS in female patients has been extensively studied [13,14,26,27], the same cannot be said for male patients [28]. Previous studies have often relied on anthropometric measurements, without adhering to national standards or considering standard deviations.

This gap in the literature underscores the need for this study. We aim to investigate and compare anthropometric parameters and growth patterns in adolescent boys and girls with AIS within the Turkish population. We intend to adhere to national standards and consider standard deviations in our analysis. Ultimately, we aspire to shed light on the influence of sexual development on physical growth and progression of AIS, gauging breast development in girls and testicular volume in boys. This study could contribute valuable insights for both research and clinical practice by offering a more sex-inclusive understanding of AIS.

Material and Methods

MEASUREMENT OF COBB ANGLE:

The Cobb angle was measured by a single experienced orthopedist using (standing) radiographs of the thoracic and lumbar spine. Scoliosis was defined as a spinal curvature with a Cobb angle of 10° or greater. Measurements were made using the classical vertebra endplate method using erect and bending radiographs [1].

MEASUREMENT OF TESTICULAR VOLUME:

In boys, the first sign of puberty is a testicular long axis of ≥2.5 cm or a testicular volume of ≥4 cm3. Testicular volume was measured using Prader’s orchidometer [29], the most widely used instrument for measuring testicular size, and was staged according to the Male External Genitalia Scale [30].

Testicular volume index per square centimeter was calculated as follows: (length×width of right testes+length×width of left testes)/2 [17].

ANTHROPOMETRIC MEASUREMENTS:

Weight and height were measured using standard measurement techniques. Measurements were read to the nearest 0.1 value (cm). The height without shoes was measured while the participants were standing upright against a wall-mounted stadiometer, head in the Frankfort horizontal plane and heels against a Harpenden stadiometer (Holtain, Crosswell, Crymych, Pembs., SA41 3UF, UK).

Measurements were read to the nearest 0.1 value (kg). Weight was measured using a digital scale (Seca pediatric digital scale, Hammer Steindamm 3–25, 22089 Hamburg, Germany), while participants were in light clothing and without shoes. Standard deviation scores were calculated for height, weight, and BMI according to the 2015 Turkish national population standards [31]. BMI was calculated using weight (in kg) divided by the squared height (m2).

BONE AGE:

Bone age was calculated using radiographs of the left hand and wrist using the standard Greulich and Pyle atlas by a single experienced pediatric endocrinologist.

STAGING OF PUBERTY:

Pubertal development was assessed using descriptive standards developed by Tanner and Marshall. According to Tanner, stage 1 refers to the prepubertal stage, while stage 5 refers to the last stage of puberty [20]. Puberty was evaluated using Tanner staging for pubic hair and breast development and Prader’s technique for testicular volume [31–33].

When adrenarche and gonadarche differed, puberty was staged after gonadarche, namely, breast development in girls and testicular volume in boys.

BMI CALCULATION:

BMI was adjusted for age and sex, and the BMI z-score was used for diagnosis. The BMI z-score was expressed as a range of standard deviations from the 50th percentile (median) value. BMI z-scores were derived from 2015 Turkish national population standards [34]. BMI (kg/m2) was calculated based on weight in kilograms divided by the square of height in meters.

STATISTICAL ANALYSIS:

Descriptive data are presented as median and interquartile ranges (25^th and 75^th percentiles) or mean±standard deviation, according to the data distribution. The normality of data was assessed with the Shapiro-Wilk test and histogram plots. The non-parametric Mann-Whitney U test was used for non-normal data. For the analyses of normally distributed continuous variables, independent-sample t tests were used. Percentage differences between AIS patients and controls were also calculated with respect to the control group. Pearson’s correlation analysis was conducted to assess the relationship between Cobb angle and bone age. Univariable logistic regression models were fitted to estimate the effect of each variable on the prediction of AIS. Furthermore, multivariable logistic regression analysis was conducted to identify independent risk factors of AIS, whereby the variables that were found to have P<0.10 in univariable analysis were included as independent variables in the model. Odds ratios (OR) along with their 95% confidence intervals (CI) were calculated. The results were assessed at a level of P<0.05 significance. The analyses were performed using the Statistical Package for Social Sciences 25.0 for Windows (IBM Corp, Armonk, NY, USA).

Results

CORRELATION:

Figure 1 displays the results of correlation analysis assessing the relationship between Cobb angle and bone age stratified by sex. A significant positive correlation was found between Cobb angle and bone age in boys (r=0.570, P<0.001), while no such correlation was observed in girls (Figure 1).

REGRESSION:

Univariate and multivariate analyses were conducted to identify factors associated with AIS, stratified by sex (Table 5). Both analyses showed that advancing pubertal stage was significantly associated with increased odds of AIS. In girls, after controlling for pubertal stage and height, bone age was negatively and significantly associated with AIS (OR: 0.763, 95% CI: 0.625–0.932, P=0.008). In boys, age and bone age were found to be significant predictors of AIS. When controlled for age, the association between bone age and AIS was negative (OR: 0.558, 95% CI: 0.318–0.979, P=0.042).

In the univariate analysis for boys, age (OR: 1.808, 95% CI: 1.483–2.203, P<0.001) and bone age (OR: 1.540, 95% CI: 1.317–1.802, P<0.001) were positively associated with AIS. However, in the multivariate analysis, when the impact of age was accounted for, the association between bone age and AIS was reversed.

Discussion

Our study illuminated the sexually dimorphic nature of AIS progression during puberty[35–37], underscoring the importance of assessing anthropometric parameters in tandem with pubertal staging. We found unique patterns of anthropometric parameters in AIS patients, distinct from those of healthy controls, which fluctuated with pubertal progression.

During adolescence, curve progression in AIS has been reported to occur during the peak of growth in female [10,11,38] and male patients [12–15,39,40]. Previous studies have reported that female patients with AIS exhibit a trend of greater curve progression [35–37,41], while male patients with AIS have a lower curve progression [4,41,42]. Probably, these studies considered skeletal maturity in both sexes only in relation to pre-menarche and menarche and not according to Tanner staging. This may also be attributed to the fact that male patients with AIS grow differently and have abnormal growth patterns during puberty compared with healthy males.

In female patients with AIS, BMI was higher than that of controls in the prepubertal phase and during the pubertal growth spurt, but it declined after puberty. This agrees with the previous studies that reported similar BMI trends in girls with AIS [43–46]. Conversely, our male patients with AIS exhibited lower BMI than their healthy counterparts only at stage 5. This novel finding has not been reported in the literature before, warranting further investigation to ascertain the biological underpinnings of this phenomenon.

Notably, our results diverged from those of previous studies, such as that by Dangerfield et al, which reported that girls with scoliosis were shorter than their healthy counterparts [47]. We found girls with AIS to be shorter during pubertal stages 1 and 5 but taller during the premenarchal stage. This discrepancy warrants further exploration.

Further analysis revealed that bone age and chronological age emerged as independent predictors of scoliosis in boys with AIS. Furthermore, a significant relationship was identified between chronological age and the Cobb angle. Our findings echo the results of Wei-Jun et al, who recognized body weight and chronological age as critical variables affecting curve size in male patients with AIS [28].

Our findings also stress the significance of pubertal staging as an essential parameter to be considered in patients with AIS. The present study adds to the growing body of evidence suggesting abnormal growth patterns in AIS patients [27], which are potentially driven by neuro-hormonal dysregulation at various biological levels.

However, the cross-sectional nature of our study constrains our ability to establish a clear temporal relationship between anthropometric parameters and AIS progression. Future longitudinal studies could provide invaluable insights into the evolution of these parameters and their correlation with curve progression in patients with AIS.

Ultimately, understanding these growth patterns and their relationship to AIS could be instrumental in establishing early intervention strategies and personalized treatment plans. Further research is required to delineate the complex interplay of factors contributing to AIS and to explore the clinical implications of these anthropometric findings.

Our findings highlight the importance of considering the pubertal stage and various anthropometric parameters in managing AIS. They also point to a possible link between AIS progression and growth patterns, providing a novel avenue for future research into the pathogenesis and management of AIS.

Conclusions

The results strongly support our hypothesis that although both male and female patients with AIS show abnormal pubertal development, male patients with AIS exhibit a different pattern of abnormality than do female patients with AIS. However, it is not entirely clear whether the results found in this study are the cause or the consequence of the deformity.