Bone Age In Boys Research Articles

Olecranon bone age assessment in puberty using a lateral elbow radiograph and a deep-learning model.

To improve pubertal bone age (BA) evaluation by developing a precise and practical elbow BA classification using the olecranon, and a deep-learning AI model. Lateral elbow radiographs taken for BA evaluation in children under 18 years were collected from January 2020 to June 2022, retrospectively. A novel classification and the olecranon BA were established based on the morphological changes in the olecranon ossification process during puberty. The olecranon BA was compared with other elbow and hand BA methods, using intraclass correlation coefficients (ICCs), and a deep-learning AI model was developed. A total of 3508 lateral elbow radiographs (mean age 9.8 ± 1.8 years) were collected. The olecranon BA showed the highest applicability (100%) and interobserver agreement (ICC 0.993) among elbow BA methods. It showed excellent reliability with Sauvegrain (0.967 in girls, 0.969 in boys) and Dimeglio (0.978 in girls, 0.978 in boys) elbow BA methods, as well as Korean standard (KS) hand BA in boys (0.917), and good reliability with KS in girls (0.896) and Greulich-Pyle (GP)/Tanner-Whitehouse (TW)3 (0.835 in girls, 0.895 in boys) hand BA methods. The AI model for olecranon BA showed an accuracy of 0.96 and a specificity of 0.98 with EfficientDet-b4. External validation showed an accuracy of 0.86 and a specificity of 0.91. The olecranon BA evaluation for puberty, requiring only a lateral elbow radiograph, showed the highest applicability and interobserver agreement, and excellent reliability with other BA evaluation methods, along with a high performance of the AI model. This AI model uses a single lateral elbow radiograph to determine bone age for puberty from the olecranon ossification center and can improve pubertal bone age assessment with the highest applicability and excellent reliability compared to previous methods. Elbow bone age is valuable for pubertal bone age assessment, but conventional methods have limitations. Olecranon bone age and its AI model showed high performances for pubertal bone age assessment. Olecranon bone age system is practical and accurate while requiring only a single lateral elbow radiograph.

Association between sex hormones and bone age in boys aged 9-18 years from China.

This study aimed to analyse the association between sex hormones and bone age (BA) in boys aged 9-18 years, both individually and interactively, and further to explore whether nutritional status may influence this association. A retrospective analysis was performed among 1382 Chinese boys with physical measurements, sexual characteristics, BA radiographs and sex hormone indicators from February 2015 to February 2022. A total of 470 (34.0%) boys had advanced BA. BA was positively associated with estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone in both advanced and normal BA groups after adjusting for age, genetic height and body mass index. Multiple logistic regression showed that after adjusting for covariates, estradiol (odds ratio [OR] = 1.66, 95% confidence interval [CI]: 1.14-2.12), LH (OR = 1.43, 95% CI: 1.04-1.96), and testosterone (OR = 1.58, 95% CI: 1.17-2.13) were significantly associated with the increased risk of advanced BA in boys, and the association was reinforced when these hormones were interactively explored. Stratified by nutritional status, the interaction between estradiol, LH, and testosterone showed a strong association with advanced BA in boys with normal weight.

Aromatase inhibitors: a useful additional therapeutic option for slowing down advanced bone age in boys with growth hormone deficiency.

Aromatase inhibitors (AIs) have been used to slow down estrogen-dependent skeletal maturation in pubertal boys with short stature. In the literature, few data evaluate the effectiveness and safety of AIs in boys with growth hormone deficiency (GHD). This study aimed to evaluate the auxologic effects and short-term laboratory profiles of combined AI and rhGH therapy for 1year in adolescent males with GHD. Male subjects between the ages of 10 and 16 with GHD from two different centers were included in the study. Patients were divided into two groups: (i) those who only used recombinant human growth hormone (rhGH) therapy (Group I; G-I) and (ii) those who also used AI therapy (anastrozole or letrozole) along with rhGH (Group II; G-II). Forty-one patients (G-I, 46%; G-II, 54%) were included in the study. All the subjects had isolated GHD. At the beginning of the treatment, the chronological ages (CAs) of the patients in the G-I and G-II groups were 11.8 (10.9-13.7) and 12.8 (12.0-14.3) years, respectively. The ratios of bone age (BA)/CA for the two groups were 0.8 (0.8-0.9) and 1.0 (0.9-1.1), respectively (p < 0.001). After the treatment, the height standard deviation (SD) scores and predicted adult height (PAH) significantly increased from baseline in all subjects in the G-I and G-II groups (p < 0.001; p < 0.001, respectively). There was no significant change in the ratio of BA/CA post-therapy in the G-I group (p = 0.1), while there was a significant decrease in the G-II group (p < 0.001). The growth velocities of the patients in the G-I and G-II groups were 9.1 (7.4-10.1) cm/year [1.5 (0.8-5.0) SD score] and 8.7 (7.5-9.9) cm/year [1.1 (0.3-3.1) SD score], respectively (p = 0.6). While post-therapy serum testosterone concentrations were seen to increase in the G-II group, none of the patients exhibited hematocrit above 50 percent, and the fasting glucose concentrations were normal. When used in addition to rhGH therapy in boys with GHD and advanced BA, AIs were observed to slow down the tempo of BA maturation after 1year, compared to those who received rhGH treatment alone. AI therapy was found to be safe during the 1-year observation period and thus could be considered for preserving growth potential in these patients.

Exaggerated Premature Adrenarche in Boys: Comparative Study of a Therapeutic Intervention With the Aromatase Inhibitor Anastrozole Versus Morning Low Dose Hydrocortisone

Abstract Background: In boys, idiopathic premature adrenarche (IPA) is defined as the appearance of pubic or axillary hair/odor before the age of 9 yrs, not due to pathology of the adrenal glands. Exaggerated Adrenarche (EXAD), occurring in 10-15% of children with IPA, is characterized by an elevated &amp;gt;10 DHEA/Δ4 ratio (theoretically indicating reduced 3-β-HSD activity) and accelerated bone age (BA) maturation, continuously increasing the projecting distance from the target height (TH) curve, beyond the one observed in the pattern of Constitutional Advancement of Growth (CAG), eventually leading to short stature (SS). It is traditionally successfully treated with a morning (6-8 am) low dose of hydrocortisone (8 mg/m2) in order to reduce the androgens produced and delay BA progression, similarly to the standard treatment of non-classical (late-onset) CAH. Third generation aromatase inhibitors (AI) have been shown to delay BA by inhibiting the peripheral aromatization of androgens and are being widely used off-label to treat short SS in boys. Aims: To evaluate the effectiveness of the AI anastrozole in delaying BA in boys with EXAD. Methods: 39 boys with advanced BA and a predicted adult height (PAH) &amp;lt;170cm and &amp;gt; -1SDS from TH) were included. Group-A (n=28) received anastrozole 1mg x 1 p.o. and group-B (n=11) low dose (8 mg/m2) hydrocortisone at 6-8 am for at least 3 yrs. All measurements were made on the same height meter by the same examiner. The two groups did not differ in terms of age at intervention onset: 8.6 in group A vs 8.74 yrs in group B, TH: 175.7 vs 175.7 cm, PAH: 168.4 vs 167.8 cm and BA advancement: +2.3 yrs in group A vs +2.4 yrs in group B. A 6-month follow-up included clinical examination, BA assessment, and laboratory tests (general blood, lipid chart, LH, FSH, TESTO, E2, E1, and complete calcium metabolism). Lumbar spine DEXA scan and X-Ray was performed on an annual basis. Results: Both groups had a statistically significant gain in PAH after 3yrs of treatment: Group A +10.3 cm (1.53 SD), p&amp;lt;0.001, and group B +7.1 cm (1.06 SD), p=0.007. Thus, group A exceeded their TH by +3cm (0.45 SDS) and group B reached -0.8cm (-0.11 SDS) from their TH, p=0.03. The reduction of BA advancement was statistically significant in both groups (p&amp;lt;0.05), with superiority of the anastrozole-treated group: at 3yrs in group A BA advancement was +0.48 yrs, and at group B +1.24 yrs (p&amp;lt;0.001). No clinical adverse events or abnormal tests were noted in any of the groups. Bone density and vertebral morphology was not affected within or between groups. Conclusions: Aromatase Inhibitors may have a place in managing exaggerated adrenarche in boys, showing superiority to traditional low-dose hydrocortisone in improving predicted adult height and delaying bone age maturation, but notably by overcoming quality of life and compliance issues associated with hydrocortisone therapy (mandatory 6-8 am).

Changes of the growth plate in children: 3-dimensional magnetic resonance imaging analysis.

Purpose This pilot study assessed changes in the growth plate and growth rates in children during a 6-month period.Methods The study included 31 healthy children (17 boys, 14 girls) under evaluation for growth retardation. Height, weight, bone age, insulin like growth factor-1 (IGF-1), and insulin like growth factor binding protein 3 (IGF-BP3) were measured at baseline and after 6 months. In addition, the diameter, thickness, and volume of the femoral and tibial growth plates were measured using magnetic resonance imaging.Results The mean bone age in boys and girls was 11.7 and 10.7 years, respectively. In boys, height (z score) (-0.2 vs. 0.0), weight (z score) (0.8 vs. 1.1), body mass index (BMI) (z score) (1.27 vs. 1.5), IGF-1 (ng/mL) (343.6 vs. 501.8), and IGF-BP3 (ng/mL) (5,088.5 vs. 5,620.0) were significantly higher after 6 months. In girls, height (z score) (-1.0 vs. -0.7), weight (z score) (-0.5 vs. 0.1), BMI (z score) (-0.02 vs. 0.3), IGF-1 (ng/mL) (329.3 vs. 524.6), and IGF-BP3 (ng/mL) (4,644.4 vs. 5,593.6) were also significantly higher after 6 months. In both sexes, the mean diameter and volume of the femoral and tibial growth plates were significantly increased 6 months later.Conclusion No significant correlation was found between changes in the growth plate and clinical parameters in children with growth retardation in this study, other than correlations of change in femoral diameter with weight and BMI. A larger, long-term study is needed to precisely evaluate the correlation between change in the growth plate and growth.

Bone age in the 21st century: is Greulich and Pyle’s atlas accurate for Israeli children?

The applicability today of Greulich and Pyle's Radiographic Atlas of Skeletal Development of the Hand and Wrist (G&P) is uncertain. The purpose of this study was to determine whether G&P is accurate in Israeli children today. Left-hand radiographs of 679 children (375 boys) ranging in age from 1day to 18years old were obtained for trauma in the period 2001-2009 and were evaluated for bone age according to G&P. Individual bone age was plotted against calendar age and smoothed to obtain the association between calendar age and bone age. Any difference was assessed with Wilcoxon signed-rank test. In girls, there was no significant difference between bone age and calendar age (P = 0.188). G&P underestimated bone age in boys <15years old (median difference, 2.3months; P < 0.0001) and overestimated bone age in boys ≥15years old (median difference, 2.9months; P = 0.0043). The largest median difference (5.4months; P = 0.0003) was seen in boys 6-10years old. The differences between calendar age and bone age according to G&P were relatively small compared with normal variance and are unlikely to be of clinical importance.

Patterns of Growth Associated With the Timing of Adiposity Rebound

This study was undertaken to evaluate the effects of age of adiposity rebound (AR) on measures of fat mass between ages 7 and 11 years, maturity, and adiposity in 458 children from a birth cohort studied to age 26 years. Patterns of growth between ages 3 and 26 years and changes in fat mass index between 7 and 11 years in groups with early (<5.5 years for boys and <5 years for girls), average (between 5.5 and 7.5 years for boys and between 5 and 7 years for girls), and late AR (> or =7.5 years for boys and > or =7 years for girls) are described. The mean z-scores for BMI, height, and weight increased between age 3 years and adolescence in the early-rebound group and decreased in the late-rebound group. The differences were maintained until adulthood for BMI and weight. Disproportionately high increases in fat mass index during growth (7-11 years), more advanced bone age in boys at age 7 years, and earlier menarche in girls were evident in the early-rebound group. The relative risks at 26 years of being overweight (BMI 25-29.9 kg/m(2)) and obese (BMI > or =30 kg/m(2)) were 2.70 (95% confidence interval (CI): 1.55, 4.66) and 5.91 (95% CI: 3.03, 11.55) respectively, using the average group as the reference. The corresponding relative risks for adult waist girths exceeding international cut points were 2.12 (95% CI: 1.09, 4.13) and 3.32 (95% CI: 1.46, 7.54). Thus, early rebound is associated with increased depositions of fat in middle childhood, and risks associated with early rebound persist at least until early adulthood.

Advanced Skeletal Maturity in Ambulatory Cerebral Palsy Patients

Both advanced and delayed bone age relative to chronological age have been described in non ambulatory children with moderate to severe cerebral palsy (CP). The purpose of our study was to assess skeletal maturation in an ambulatory CP population and determine the affects of body mass index (BMI), type of CP, and Gross Motor Function Classification System (GMFCS) on skeletal maturity. A retrospective chart and radiograph review was performed on 51 patients with ambulatory CP. A control group of 50 patients was also analyzed. Age, sex, height, weight, type of CP, and GMFCS were recorded from the chart. The height and weight were used to calculate BMI. Bone age was determined using the Oxford method. Statistical analysis for the data included descriptive statistics with bivariate and multivariate regression analyses. Significance was determined as P < 0.05. There were 26 boys and 25 girls. All CP patients were independent ambulators. The mean chronological age was 7.1 years for boys and 8.6 years for girls. The mean bone age was 9.9 years for boys and 10.6 years for girls. Overall, 48 (94%) of 51 patients had advanced bone age compared with chronological age. Bone age was significantly advanced compared with chronological age for boys (P = 0.033) and showed a trend toward significance in girls (P = 0.079). Bone age was advanced compared with our control population in both sexes. In multivariate analysis, quadriplegic CP type showed a trend toward significance (P = 0.066), and GMFCS III was significantly associated with advanced bone age in boys (P = 0.011). In girls, quadriplegic CP type and BMI of less than 15 were significantly associated with advanced bone age (P < 0.05 in both). Our results demonstrated that most of the ambulatory CP patients had advanced bone age compared with chronological age. Quadriplegic CP type in boys and girls contributed to advanced bone age. GMFCS III and a low BMI also contributed to advanced bone age in boys and girls, respectively. Understanding factors that lead to either delayed or advanced skeletal maturation is important in planning the appropriate timing for orthopaedic surgical intervention.

Clinical Utility of Serum E2 Assayed by Means of a High-Sensitivity Kit in Children

To evaluate the usefulness of a high-sensitivity assay kit for E2, we measured the serum E2 levels in children. The value in a girl with true central precocious puberty was also evaluated before the LH-RH analogue treatment. The study subjects were 36 boys, ranging in age from 1 yr and 9 mo to 17 yr and 6 mo and 46 girls, ranging in age from 1 yr to 15 yr and 6 mo. The minimal detection limit was 1.4 pg/ml. The serum E2 level in the boys and that in girls were 10.8 ± 3.1 pg/ml (mean ± SEM) and 20.7 ± 10.7 pg/ml, respectively. The E2 level was correlated closely with bone age and chronological age. Even when the range of serum E2 was limited to an undetectable level (<10 pg/ml) by the conventional assay, the logarithmic value for the E2 concentration was correlated with bone age in boys (r=0.734, p<0.05) and in girls (r=0.404, p<0.05). The E2 level in girls with partial and true precocious puberty ranged from 2.6 to 8.7 pg/ml. In a patient, who was originally considered as premature thelarche and later turned out to be true central precocious puberty, the serum E2 level was 3.7 pg/ml before therapy, suggesting that high sensitivity to estrogen was the cause of the condition. With LH-RH analogue treatment, the E2 level declined to below the detection limit and the bone age did not change for 1 yr without loss of linear growth. These results suggest that the high-sensitivity kit is useful for monitoring the pathophysiology of E2 in children.

Relationship of somatomedin-C concentration to bone age in boys with constitutional delay of growth.

Serum somatomedin-C (Sm-C) levels increase sharply during puberty, leading to difficulty in the interpretation of Sm-C values obtained from children who exhibit a discrepancy between chronological age (CA) and pubertal development. To evaluate the utility of assessing Sm-C levels on the basis of bone age (BA), we measured serum Sm-C levels in 44 boys with constitutional delay of growth (CDG). Levels of Sm-C were compared with the normative data of the Nichols Institute Reference Laboratories (NIRL), Los Angeles, by age category, substituting BA for CA. We found the mean Sm-C level in boys with CDG to be lower than that for NIRL normal subjects in each age category for both CA and BA, but the regression curve for Sm-C levels based on BA more closely approximated the NIRL regression curve than did the curve based on CA. The rise in Sm-C levels observed in NIRL normal subjects between CA 13 to 14 years is delayed in boys with CDG until CA 15 to 17 years only when a correction for BA is not made. We conclude that in boys with CDG, Sm-C levels should be interpreted on the basis of BA rather than CA, especially during the peripubertal period. The observation of blunted Sm-C levels in all age categories, even when BA was used, suggests that short children with presumed CDG may be at high risk for a "nonclassic" form of growth hormone deficiency.

Bone age in short boys and tall girls.

In apparently healthy boys below the third percentile in height, the agreement of three radiologists' assessments of bone age from roentgenograms of the wrist and hand was poor, with only 62% concurrence of readings within six months. In 90% of the short boys, bone age was delayed more than 6 months (average delay, 29 months). In girls above the 97th percentile in height, the agreement between radiologists' readings of the same roentgenogram was closer with 75% concurrence within six months. The average difference between bone age and chronological age in the tall girls was only four months. The results suggest that certain standards, while adequate for the evaluation of tall girls, are not satisfactory for the estimation of bone age in boys below the third percentile in height.