Bone Age Research Articles

Associations of fetal and infant growth with pubertal timing

ObjectiveImpaired fetal and infant growth may cause alterations in developmental programming of the hypothalamic–pituitary–gonadal axis and subsequently pubertal development. We aimed to assess associations between fetal and infant growth and...

Descriptive Epidemiology of Complete ACL Tears in the Skeletally Immature Population: A Prospective Multicenter PLUTO Study.

Anterior cruciate ligament (ACL) injuries are common in pediatric and adolescent patients. Understanding this population's injury characteristics and treatment strategies is vital for managing this high-risk group. To report the descriptive epidemiology and treatment strategies of a large cohort of skeletally immature patients with complete ACL tears. Cross-sectional study; Level of evidence, 2. Consecutive skeletally immature patients diagnosed with complete ACL tears were enrolled at 10 institutions across the United States. Treatment was provided by 1 of 23 participating orthopaedic surgeons. Patient characteristics (chronological and skeletal age, sex, race, and ethnicity) as well as anthropometric measures, mechanism of injury, and ACL treatment type were collected. A total of 749 skeletally immature participants were included in the final cohort; the mean chronological age was 12.9 years, and 62% were male. The mean skeletal age (13.2 years) was a mean of 0.34 years (4 months) higher than the mean chronological age (P < .001). Tanner staging revealed that 18% of participants were Tanner stage 1, 20% were Tanner stage 2, 28% were Tanner stage 3, 30% were Tanner stage 4, and 4% were Tanner stage 5. Five percent of participants reported a previous ipsilateral knee injury, and 30% had a family history of ACL injuries. Sport was the predominant mechanism of injury (89%), with noncontact injuries the most common (64%). The most common sport resulting in an ACL tear among boys was American football (41%) and among girls was soccer (44%). Overall, 99.9% of skeletally immature patients were treated surgically by 1 of 4 reconstruction techniques: transphyseal (53%), partial transphyseal (7%), physeal-sparing all-epiphyseal (13%), and physeal-sparing iliotibial band (ITB) (27%). The most common surgical techniques for patients with a skeletal age <13 years were physeal sparing with ITB (56%) and all-epiphyseal (22%), while in patients with a skeletal age ≥13 years, transphyseal (71%) and physeal sparing with ITB (12%) were the most common. Overall, 57% of patients who underwent ACL reconstruction had arthroscopically documented meniscal tears, with high rates of meniscal repair (90% medial tears and 66% lateral tears). Almost all skeletally immature patients with ACL tears were injured during sports, surgical treatment was overwhelmingly the treatment of choice, and preferred surgical techniques varied based on skeletal ages.

Testosterone Modulation of Muscle Transcriptomic Profile During Lifestyle Therapy in Older Men with Obesity and Hypogonadism

ABSTRACTBackgroundTestosterone replacement therapy (TRT) added to lifestyle therapy can mitigate weight‐loss–induced reduction of muscle mass and bone mineral density (BMD) in older men with obesity and hypogonadism.ObjectiveTo investigate the molecular mechanisms underlying the attenuation of muscle and BMD loss in response to TRT during intensive lifestyle intervention in this high‐risk older population.MethodsAmong 83 older (≥ 65 years) men with obesity (BMI ≥ 30 kg/m2) and hypogonadism (early AM testosterone persistently &lt; 300 ng/dL) associated with frailty (Modified Physical Performance Test score ≤ 31) randomized into 26‐week lifestyle therapy plus testosterone (LT+TRT) or placebo (LT+Pbo) in the LITROS trial, 38 underwent serial muscle biopsies for the muscle transcriptomics substudy.ResultsDespite similar ~10% weight loss, lean body mass and thigh muscle volume decreased less in LT+TRT than LT+Pbo (−2% vs. −4%, respectively; p = 0.04). Hip BMD was preserved in LT+TRT compared with LT+Pbo (0.4% vs. −1.3%; p = 0.03). Muscle strength increased similarly in LT+TRT and LT+Pbo (23% vs. 24%; p = 0.95). Total testosterone increased more in LT+TRT than LT+Pbo (133% vs. 32%; p = 0.005). Based on Next Generation Sequencing, of the 39 160 and 39 115 genes detected in LT+TRT and LT+Pbo, respectively, 195 were differentially expressed in LT+TRT and 158 in LT+Pbo. Gene Ontology enrichment analyses revealed that in LT+TRT, just four muscle‐related pathways (muscle organ development, muscle organ morphogenesis, regulation of skeletal muscle contraction, muscle atrophy) were downregulated and one pathway (muscle system process) was upregulated. In contrast, in LT+Pbo, nine muscle‐related pathways (muscle system process, muscle tissue development, muscle organ development, skeletal muscle tissue development, skeletal muscle organ development, skeletal muscle cell differentiation, muscle organ morphogenesis, response to stimuli involved in regulation of muscle adaptation, muscle atrophy) and one pathway related to bone (bone mineralization involved in bone maturation) were downregulated. Muscle system process was upregulated in LT+TRT but downregulated in LT+Pbo. RT‐PCR analyses showed that LT+TRT resulted in a higher expression of MYOD1 (p = 0.02) and WNT4 (p = 0.02), key genes involved in muscle and bone metabolism, respectively, compared with LT+Pbo. We also observed significantly higher mRNA expression of MYBPH (p = 0.006), SCN3B (p = 0.02) and DSC2 (p = 0.01), genes involved in the muscle system process, in response to LT+TRT compared with LT+Pbo.ConclusionThe addition of TRT to lifestyle therapy mitigates the weight‐loss–induced reduction of muscle mass and BMD via countering the weight‐loss–induced downregulation of genes involved in muscle and bone anabolism.

O-03 DELAYED PUBERTY AND GIANT PROLACTINOMA IN A 14-YEAR-OLD GIRL WITH A HISTORY OF ANOREXIA NERVOSA

Abstract Introduction Giant prolactinomas are rare, especially in children and adolescents and often resistant to the recommended first-line cabergoline monotherapy. In addition, possible second line guideline treatment recommendations (surgery, radiotherapy, temozolomide) are not suitable. Clinical Case A 14-year-old girl (51kg/155,7cm/BMI 18.4 kg/m2, bone age 14.37) was referred to pediatric endocrinologist because of primary amenorrhea and delayed puberty. Two years earlier, she underwent a brief episode of anorectic behavior (rapid weight loss of 15.4 kg) but recovered before the age of 14. Results Clinical examination was normal, excluding Tanner stage M2P3. No galactorrhea was evident. Laboratory work-up revealed hyperprolactinemia (S-PRL 26 817 mU/l (86-324)). Estradiol and gonadotropins were consistent with the pubertal stage (S-Estdiol 0.02 nmol/l; S-FSH 3.2 U/l, S-LH &amp;lt;1.0 U/l). Thyroid function and cortisol secretion (P-Corsol 411 nmol/l, P-ACTH 21 ng/l) were normal, but S-TPOAb elevated at 350 kU/l (&amp;lt;34 kU/l). Genetic testing for AIP, MEN1, GNAS1, MAX, SDHA, SDHC, SDHD, SDHAF2, PRKAR1a mutations was negative. Abdominal ultrasound revealed a small uterus. Brain MRI showed a giant prolactinoma, (21x30x40 mm; Fig. 1A) which extended to the dorsum sellae, infiltrated the left cavernous sinus, filled the suprasellar cistern compressed the optic chiasm. Neuro-ophthalmological examination; visual acuity, fields was normal. Prolactin level was repeatedly high (30 210 mU/l; 78% (23 672 mU/l) biologically active. The patient was put on cabergoline (0,5mg/week) and the dose was doubled one month later as the prolactin remained high (14 509 mU/l). Tumor size was unchanged on 4 months follow-up MRI. The case was discussed at the multidisciplinary pituitary tumor board. Neither surgery nor radiotherapy were recommended and temozolomide was unsuitable. Cabergoline was increased to 1,5mg/week. At 5 months, the patient had primary hypothyroidism (P-TSH 5,00 mU/l, free-T4 11; S-PRL 4509 mU/l) and was put on L-T4 (50µg/day). 11C-methionine PET/MRI demonstrated significant uptake throughout the tumor tissue. Tumor size had decreased slightly. Cabergoline was increased to 3mg/week; 11 months after initiation of the treatment, S-PRL had decreased to 4800mU/l. Though no clinical signs of puberty were evident, estradiol and gonadotropin levels had risen (S-Estdiol 0.21 nmol/l, LH 18 IU/l, FSH 7.4 IU/l). Cabergoline was increased to 3.5mg/week. After 13 months of treatment, S-PRL was 3523, S-Estdiol 0.08, FSH 5.9, LH 7.7, TSH 0.08, free-T4 17. Cabergoline was increased to 4mg/week. Next examination, including MRI and laboratory tests, is scheduled 2 months later. Conclusion Treatment of adolescents with giant prolactinoma is challenging. There is an unmet need for second line tailored treatments, such as combined D2 and SST2&amp;5 receptor agonist therapy (cabergoline+pasireotide), which, for this case, is the planned second line experimental treatment.Figure 1:

Skeletal progenitor LRP1 deficiency causes severe and persistent skeletal defects with Wnt pathway dysregulation

Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional endocytic receptor whose dysfunction is linked to developmental dysplasia of the hip, osteoporosis and osteoarthritis. Our work addresses the critical question of how these skeletal pathologies emerge. Here, we show the abundant expression of LRP1 in skeletal progenitor cells at mouse embryonic stage E10.5 and onwards, especially in the perichondrium, the stem cell layer surrounding developing limbs essential for bone formation. Lrp1 deficiency in these stem cells causes joint fusion, malformation of cartilage/bone template and markedly delayed or lack of primary ossification. These abnormalities, which resemble phenotypes associated with Wnt signalling pathways, result in severe and persistent skeletal defects including a severe deficit in hip joint and patella, and markedly deformed and low-density long bones leading to dwarfism and impaired mobility. Mechanistically, we show that LRP1 regulates core non-canonical Wnt/planar cell polarity (PCP) components that may explain the malformation of long bones. LRP1 directly binds to Wnt5a, facilitates its cell-association and endocytic degradation and recycling. In the developing limbs, LRP1 partially colocalises with Wnt5a and its deficiency alters abundance and distribution of Wnt5a and Vangl2. Finally, using Xenopus as a model system, we show the regulatory role for LRP1 in Wnt/PCP signalling. We propose that in skeletal progenitors, LRP1 plays a critical role in formation and maturity of multiple bones and joints by regulating Wnt signalling, providing novel insights into the fundamental processes of morphogenesis and the emergence of skeletal pathologies.

The efficacy and safety of rhGH treatment combined with letrozole/GnRHa in adolescent boys

ObjectiveIn boys during puberty who were undergoing recombinant human growth hormone (rhGH) treatment, we compared the therapeutic efficacy on growth, and any adverse reactions, of co-therapy with either letrozole or gonadotropin-releasing hormone analog (GnRHa).MethodsFifty-six pubertal growth hormone deficiency (GHD) boys were studied, they were treated with the combination of letrozole and rhGH (letrozole group, n = 28) or the combination of GnRHa and rhGH (GnRHa group, n = 28) for at least one year. Eighteen patients in the letrozole group and seventeen patients in the GnRHa group attained final adult height (FAH).ResultsThe increase in height of the letrozole group was significantly more than the GnRHa group both in the first year [(10.37 ± 2.19) vs. (7.78 ± 1.55) cm] and at two years [(18.82 ± 2.49) vs. (13.84 ± 2.17) cm] (p < 0.05), however, there was no significant group difference in the advancement of bone age (BA) of in the first year or at two years (p > 0.05). The mean FAH in two groups were similar, but the treatment duration of the letrozole group was significantly less than GnRHa group. There was a significant body mass index (BMI) SDS increase in the letrozole vs. GnRHa groups. Of concern, bone mineral density (BMD) decreased in both groups after treatment, but more so in the letrozole cohort.ConclusionThe combination of letrozole/rhGH in pubertal GHD boys was similar to GnRHa/rhGH in terms of the progression of BA and FAH, but the former co-therapy was superior in the gain of height. Disconcertingly, however, this combination may adversely affect BMI and BMD.Clinical trial registration numberChiCTR2300068405.

Bone Age Assessment Using Various Medical Imaging Techniques Enhanced by Artificial Intelligence

Bone Age Assessment Using Various Medical Imaging Techniques Enhanced by Artificial Intelligence

Tridimensional Evaluation of Condyle-Fossa Relationship in Mexican Population Using CBCT

Background: This study aims to compare the condylar position in Mexican population with the values of Ikeda Spatial Condyle Analysis with different sagittal skeletal pattern, age and sex using a cone beam computed tomography (CBCT). Objective: To evaluate the condyle-fossa relationship in patients with skeletal patterns and sex using Ikeda Spatial Condyle Analysis assessed with CBCT. Materials and Methods: An observational analytical cross-sectional study, 86 condyles CBCT images were used for this study (August 2023- December 2024). The patients were divided into 3 groups according to 3 criteria: age (12-60 years old with intervals of 5 years); sex (female and male); and skeletal pattern as ANB classification (Class I, Class II, and Class III). Temporomandibular joint space (TMJS): (SAS, sagittal anterior space; SSS, sagittal superior space; SPS, sagittal posterior space; CMS, coronal medial space; CLS, coronal lateral space and CCS, coronal central space) were measured and compared. Statistical analyses were performed using two-sample T test, Mu Test, and Anderson- Darling probability test (p&lt;0.05). Results: The mean age of the participants (n = 43) was 30.9 ± 10.9 years (62.7% female). Differences in condyle-fossa relationships were significantly different between Mexican population and Ikeda Condyle Analysis values (p &lt; 0.05). The mean values showed no statistical differences according to sex or sagittal skeletal pattern. The sagittal measurements showed the mean ratio of SAS (2.1+/- 0.6), SSS and SPS (2.5+/-0.7) and (1.8+/- 0.5), respectively. The coronal measurements showed the mean ratio of CMS (2.3+/- 0.7), CCS and CLS (2.5+/- 0.8) and (2.1+/- 0.6), respectively. Conclusions: The Mexican tridimensional condylar position showed significant differences compared with the Ikeda condylar position. These results can be associated to racial anatomical differences. The condyle-fossa relationship values for skeletal pattern; Left / Right condyles and sex, showed ..

Clinical Manifestations and Challenges in Adolescent and Adult Females With Classic Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency.

Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is a rare genetic condition that results in cortisol deficiency and excess production of adrenal androgens. While the introduction of newborn screening for CAH has reduced morbidity and mortality, management of CAH remains challenging. Lifelong treatment with glucocorticoids is required to replace the endogenous cortisol deficiency and reduce excess adrenal androgens. Undertreatment or overtreatment with glucocorticoids can lead to multiple disease- and treatment-related comorbidities, including impaired growth and compromised final height, menstrual irregularities and reduced fertility in females, and long-term cardiometabolic complications. In addition to avoiding adrenal crisis and sudden death, treatment goals in adolescent females with CAH are to obtain normal growth and bone maturation and normal timing of puberty. Management of adolescents is particularly challenging due to changes in growth and sex hormone levels that can lead to inadequate suppression of adrenal androgens and increasing independence that can affect treatment adherence. During the transition to adult care, treatment goals focus on preventing symptoms of hyperandrogenism, preserving menstrual regularity and fertility, and providing education and support for issues related to sexuality, atypical genitalia, and/or complications from previous surgical treatment. In addition, patients must be monitored continuously to prevent long-term complications such as decreased bone mineral density, obesity, diabetes, and hypertension. In this review, we discuss the challenges faced by adolescent and adult females with CAH and provide guidance to health-care professionals to help patients to navigate these challenges.

Correlation Between Handgrip Strength and Bone Density and Fragility Fracture Risk Among Older Adults: A Cross-Sectional Study.

Population aging has led to a surge in elderly care needs worldwide. Bone aging, skeletal muscle degeneration, and osteoporosis pose critical health challenges for the elderly. The process of bone and skeletal muscle aging not only impacts the functional abilities but also increases fragility fracture risk. Although a negative correlation between handgrip strength and fragility fracture risk has been identified in elderly populations, there is a lack of related research in Taiwan. This cross-sectional study was designed to investigate the association between handgrip strength and two outcome variables, bone density and risk of fragility fracture, in Taiwanese individuals aged 65 years and older with low bone mass. A total of 548 older adults, including 84 men and 464 women, were recruited between August 2019 and July 2021. Bone mineral density T-scores acquired using dual-energy X-ray absorptiometry scan, the total score for the Taiwan-specific Fracture Risk Assessment (FRAX) tool, and bilateral handgrip strength acquired using a digital hand dynamometer were recorded along with other factors such as comorbidities, dietary habits, and daily activities. In this study, the mean age was 70.9 (SD = 5.6) years, mean bone mass index was 24.1 (SD = 3.5) kg/m2, mean FRAX main fracture risk score was 19.5% (SD = 8.3), and mean FRAX hip fracture risk score was 7.7% (SD = 5.7). Lumbar and hip T-scores were both significantly correlated with both dominant and nondominant handgrip strength in older woman. Older age; both lower hip and spine T-scores; both lower dominant and nondominant handgrip strengths; having Type 2 diabetes, coronary artery disease, or chronic hepatic disease; and lacking a steady job were significantly associated with a higher risk of fragility fracture. The results of this study provide important information regarding the correlation between handgrip strength and several variables, including bone mineral density T-score, FRAX score, comorbidities, and job status, among older adults. Notably, these correlations were found to be particularly strong in the female participants. This information may be used to facilitate the early identification of elderly individuals at a high risk of fragility fractures, enabling the timely development of preventive nursing strategies and the provision of targeted interventions.

Bone Marrow Stromal Cells Generate a Pro-Healing Inflammasome When Cultured on Titanium-Aluminum-Vanadium Surfaces with Microscale/Nanoscale Structural Features.

The surface topography and chemistry of titanium-aluminum-vanadium (Ti6Al4V) implants play critical roles in the osteoblast differentiation of human bone marrow stromal cells (MSCs) and the creation of an osteogenic microenvironment. To assess the effects of a microscale/nanoscale (MN) topography, this study compared the effects of MN-modified, anodized, and smooth Ti6Al4V surfaces on MSC response, and for the first time, directly contrasted MN-induced osteoblast differentiation with culture on tissue culture polystyrene (TCPS) in osteogenic medium (OM). Surface characterization revealed distinct differences in microroughness, composition, and topography among the Ti6Al4V substrates. MSCs on MN surfaces exhibited enhanced osteoblastic differentiation, evidenced by increased expression of RUNX2, SP7, BGLAP, BMP2, and BMPR1A (fold increases: 3.2, 1.8, 1.4, 1.3, and 1.2). The MN surface also induced a pro-healing inflammasome with upregulation of anti-inflammatory mediators (170-200% increase) and downregulation of pro-inflammatory factors (40-82% reduction). Integrin expression shifted towards osteoblast-associated integrins on MN surfaces. RNA-seq analysis revealed distinct gene expression profiles between MSCs on MN surfaces and those in OM, with only 199 shared genes out of over 1000 differentially expressed genes. Pathway analysis showed that MN surfaces promoted bone formation, maturation, and remodeling through non-canonical Wnt signaling, while OM stimulated endochondral bone development and mineralization via canonical Wnt3a signaling. These findings highlight the importance of Ti6Al4V surface properties in directing MSC differentiation and indicate that MN-modified surfaces act via signaling pathways that differ from OM culture methods, more accurately mimicking peri-implant osteogenesis in vivo.

Development of a disease diagnostic model to predict the occurrence of central precocious puberty of female.

To develop a clinical model for predicting the occurrence of Central Precocious Puberty based on the breast development outcomes in chinese girls. This is a retrospective study, which included a total of 1,001 girls aged 6-9 years old who visited the outpatient clinic of Beijing Children's Hospital from January 2017 to October 2022 for "breast development". Participants were categorized into pubertal development (PD) cohort and simple premature breast development (PT) according to the criteria, and information was collected and tested for relevant indicators. After dealing with missing data, logistic regression, LASSO regression and random forest were used to screen the variables, and support vector machine models were built with SMOTE oversampling and ten-fold cross-validation to assess the effectiveness of the models in the training and validation sets. 1,001 girls were included in the analysis, of whom 369 (36.9 %) were diagnosed with PD and 632 (63.1 %) with PT. Body mass index (BMI), bone age (BA), luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), uterine diameter, and ovary volume were identified as the final predictor variables by three variable screening methods. The AUC of the constructed disease diagnostic model was 0.9457 in the developmental cohort and 0.8357 inthe external validation group, and sensitivity analyses revealed that the performance of the constructed models with different variable selection strategies was similar. A disease diagnostic model was developed that may help predict a girl's risk of diagnosing central precocious puberty.

Ultrasonographic examination of the maturational effect of maternal vitamin D use on fetal clavicle bone development

AimThis study aimed to evaluate the effect of maternal vitamin D use during intrauterine life on fetal bone development using ultrasonographic image processing techniques.Materials and methodsWe evaluated 52 pregnant women receiving vitamin D supplementation and 50 who refused vitamin D supplementation. Ultrasonographic imaging was performed on the fetal clavicle at 37–40 weeks of gestation. The fetal clavicle images were compared with adult male clavicle images. The texture features obtained from these images were used for analysis.ResultsNo difference was observed in bone formation and destruction markers between the two groups. However, the texture analysis of ultrasonographic images revealed similarities in the characteristics of fetal clavicles in pregnant women receiving vitamin D supplementation and those of adult male clavicles.ConclusionsVitamin D supplementation in pregnancy has significant positive effects on fetal bone maturation besides contributing to maternal bone health. Texture feature analyses using ultrasonographic images successfully demonstrated fetal bone maturation.

Construction of a Simplified Bone Age Assessment Model in Chinese Children Aged 3-18 Years.

Bone age assessment (BAA) is critical for pediatric endocrinology. Traditional methods are complex and time-consuming, and current computer-aided systems have made progress but still lacking in robustness. Develop simplified BAA methods to aid pediatricians in quick clinical assessments. Overall, 5,551 left-hand X-ray images were collected from a cross-sectional survey in 2022- 2023. Bone age (BA) was assessed using the Tanner-Whitehouse 3-China/radius-ulna-short bone (TW3-C-RUS) method. The linear regression models were constructed with BA as the dependent variable and 13 RUS bones' grades as independent variables. A cross-sectional survey in Beijing, China. 5,551 children aged 3-18 years. Model accuracy was evaluated by R², residuals, and root mean square error (RMSE), and BA with an error margin ≤0.5 years. When bone grades were consistent, a single or few bones may serve as proxies for BA, such as metacarpals and phalanges reached grade 6, the BA for boys and girls were 13.0-13.5 years and 10.9-11.5 years, respectively. When bone grades were inconsistent, regression models were needed. Comparatively, the three-bone models have advantages and are proposed for clinically simplified BAA. The simplified three-bone model (radius, ulna, and metacarpal I) yielded an R² > 0.94 and an RMSE < 0.5 years. When considering puberty stages, specific bone combination models can further improve assessment accuracy. These three-bone models could be useful for rapid BAA, with improved accuracy when puberty stages is included. Further validation is warranted to test their robustness across populations and scenarios.

Short-acting growth hormone supplementation for bone age and growth rate in children with idiopathic short stature: a meta-analysis

ObjectiveTo explore the effect of short-acting growth hormone (GH) supplementation on bone age and growth rate of children with idiopathic short stature.MethodsThe authoritative databases such as PubMed, Medline, and Web of Science were extensively searched through the systematic and comprehensive literature retrieval strategy to compile the clinical research data on the treatment of idiopathic short stature with short-acting GH. The study will be strictly screened to ensure that all enrolled research subjects are patients with idiopathic short stature, and the intervention method is defined as short-acting GH replacement therapy, and a reasonable control group is set, such as placebo treatment, to ensure the scientificity and comparability of research results. Outcome index data such as basic characteristics, sample size, follow-up time, and total effective rate of the included studies were extracted. In this study, RevMan 5.3, a professional statistical software tool, was used to systematically perform the meta-analysis process. Weighted average difference (WMD) was calculated as the primary outcome to evaluate the effect of bone age and growth rate, and the WAD in adverse reactions was considered as the secondary outcome.ResultsNine studies were included in the study, and 491 patients with idiopathic short stature were included in the study. The results of the meta-analysis showed that there was no significant difference in bone age but a significant difference in growth rate when compared with the control group.ConclusionShort-acting GH supplementation can significantly improve the growth rate of children with idiopathic short stature, but has little effect on bone age.

Impact of Maxillomandibular Sagittal Variations on Upper Airway Dimensions: A Retrospective Cross-sectional CBCT Evaluation.

This study aimed to analyze the upper airway dimensions in adult patients with different anteroposterior (sagittal) skeletal malocclusions (class I, II, and III) using cone beam computed tomography (CBCT) imaging. This retrospective cross-sectional study involved 90 CBCT records from adult subjects who were categorized into three skeletal groups based on their ANB values: Class I (n = 30), class II (n = 30), and class III (n = 30) and were evaluated. The following upper airway measurements were considered: oropharyngeal airway volume, hypopharyngeal airway volume, pharyngeal airway volume, oropharyngeal airway length, hypopharyngeal airway length, pharyngeal airway length, the most constricted site of the pharyngeal airway, and the most constricted cross-sectional area (MIN-CSA) of the pharyngeal airway. Additionally, the volume of the intraoral airway was determined. Pearson's correlation test was employed to evaluate the relationship between age and upper airway dimensions. Significant differences in upper airway volume were found among skeletal groups in the hypopharyngeal (p = 0.034) and pharyngeal (p = 0.004) regions, with class III patients showing larger volumes compared to class II. Oropharyngeal (p = 0.044) and pharyngeal (p = 0.011) lengths were shorter in class III than in class I. In contrast, the narrowest cross-sectional area of the pharyngeal airway was larger in class III compared to class II (p = 0.003) and class I (p = 0.032). Class III patients had a significantly greater intraoral space volume than class II patients (p = 0.036). The present study found significant differences in upper airway dimensions among adults with varying maxillomandibular sagittal relationships. Class III patients had larger hypopharyngeal and pharyngeal volumes, but shorter oropharyngeal and pharyngeal lengths compared to other classes. The narrowest pharyngeal area was larger in class III, with gender and age also influencing airway dimensions. These findings underscore the need to consider skeletal relationships, gender, and age in airway assessments. Accordingly, these factors can help clinicians better understand the correlation between airway dimensions and jaw position for accurate diagnosis and treatment planning of orthodontic and surgical interventions. How to cite this article: Aldhorae K, Ishaq R, Alhaidary S, et al. Impact of Maxillomandibular Sagittal Variations on Upper Airway Dimensions: A Retrospective Cross-sectional CBCT Evaluation. J Contemp Dent Pract 2024;25(10):955-962.

Biological Behavior of Bioactive Glasses SinGlass (45S5) and SinGlass High (F18) in the Repair of Critical Bone Defects.

This study evaluated the osteogenic potential of the bioactive glasses SinGlass (45S5) and SinGlass High (F18) in regenerating critical bone defects in rat calvaria. Both biomaterials promoted new bone formation around the particles, with the SinGlass High (F18) group exhibiting a higher rate of bone maturation. Histomorphological and birefringence analyses revealed better organization of the newly formed bone in the biomaterial-treated groups, and immunohistochemistry indicated the expression of osteogenic markers such as osteocalcin, immunostaining for bone morphogenetic protein 2 (BMP 2), and immunostaining for bone morphogenetic protein 4 (BMP 4). Microtomography computadorized (Micro-CT) revealed centripetal bone formation in both groups, with greater integration of the particles into the surrounding bone tissue. The superior performance of SinGlass High (F18) was attributed to its higher potassium and magnesium content, which enhance osteoconductivity. After 42 days, the SinGlass High (F18) group showed the highest percentage of new bone formation, in line with previous studies. Although our results are promising, the limited follow-up period and use of a single animal model highlight the need for further research to validate clinical applicability. SinGlass High (F18) appears to be a viable alternative to autografts in bone repair, with potential to improve tissue integration and accelerate recovery.

Enhancing the Implant Osteointegration via Supramolecular Co-Assembly Coating with Early Immunomodulation and Cell Colonization.

Osteointegration, the effective coupling between an implant and bone tissue, is a highly intricate biological process. The initial stages of bone-related immunomodulation and cellular colonization play crucial roles, but have received limited attention. Herein, a novel supramolecular co-assembled coating of strontium (Sr)-doped metal polyphenol networks (MPN) modified with c(RGDfc) is developed and well-characterized, for eliciting an early immunomodulation and cellular colonization. The results showed that the (Sr-MPN)@RGD coating significantly regulated the polarization of macrophages to the M2 phenotype by controllable release of Sr, and promote the initial adhesion of bone marrow mesenchymal stem cells (BMSCs) by RGD presented on MPN. Notably, the (Sr-MPN)@RGD attenuated osteoclast differentiation and oxidative stress as well as enhanced osteoblast differentiation and angiogenesis due to macrophage polarization toward M2 phenotype, which in turn has a profound effect on neighboring cells through paracrine signaling. In vivo results showed that the (Sr-MPN)@RGD coating manifested superior osseointegration and bone maturation to the bare Ti-rod or Ti-rod coated with MPN and Sr-MPN. This work contributed to the design of multifunctional implant coatings that address the complex biological process of osteointegration from the perspective of orchestrating stem cell recruitment with immunomodulatory strategies.

Clinical, Biochemical and Molecular Characteristics of Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease caused by the deficiency of one of the enzymes involved in cortisol synthesis. Between 90% and 99% of cases of CAH are caused by 21-hydroxylase deficiency (21-OHD) caused by mutations in CYP21A2. Although 21-OHD has been historically divided into classical and non-classical forms, it is now thought to show a continuous phenotype. In the classical form, the external genitalia in females becomes virilized to varying degrees. If the disease is not recognized, salt wasting crises in the classical form may threaten life in neonates. Children experience accelerated somatic growth, increased bone age, and premature pubic hair in the simple virilizing form of classical 21-OHD. Female adolescents may present with severe acne, hirsutism, androgenic alopecia, menstrual irregularity or primary amenorrhea in the non-classical form. Diagnosis of CAH is made by clinical, biochemical and molecular genetic evaluation. In cases of 21-OHD, the diagnosis is based on the 17-hydroxyprogesterone (17-OHP) level being above 1000 ng/dL, measured early in the morning. In cases with borderline 17-OHP levels (200-1000 ng/dL), it is recommended to perform an adrenocorticotropic hormone (ACTH) stimulation test. Genotyping in cases with CAH should be performed if the adrenocortical profile is suspicious or if the ACTH stimulation test cannot be performed completely. After diagnosis, determining the carrier status of the parents and determining which parent the mutation was passed on from will help in interpreting the genetic results and determining the risk of recurrence in subsequent pregnancies.

Treatment and Follow-up of Congenital Adrenal Hyperplasia Due to 21-hydroxylase Deficiency in Childhood and Adolescence

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease caused by the deficiency of one of the enzymes involved in cortisol synthesis. More than 95% of the cases occur as a result of defects in the gene encoding 21-hydroxylase (CYP21A2). 21-hydroxylase deficiency has been divided into classical and non-classical forms. In the treatment of classical CAH, it is necessary to replace both glucocorticoid (GC) and mineralocorticoid hormones to prevent salt wasting crisis and reduce excessive corticotropin. In addition to biochemical measurements to evaluate the adequacy of GC and mineralocorticoid treatment; growth rate, body weight, blood pressure and physical examination should be evaluated regularly. There is insufficient data regarding the use of continuous slow-release or modified-release hydrocortisone (HC) preparations and continuous subcutaneous HC infusion, additional/alternative treatment approaches, and cell-based therapies and gene editing technology in children with CAH. GC therapy is recommended in children with inappropriately early onset and rapidly progressing pubarche or accelerated bone age progression, and in adolescents with non-classical CAH (NCCAH) who have overt virilization. In patients with NCCAH, stress doses of HC is recommended for major surgery, trauma, or childbirth but only if the patient has a suboptimal cortisol response to the adrenocorticotropic hormone test. Here, members of the ‘Adrenal Working Group’ of ‘The Turkish Society for Pediatric Endocrinology and Diabetes’ present an evidence-based review with good practice points and recommendations for optimize treatment, and follow-up of children with CAH due to 21-hydroxylase deficiency in the light of the most recent evidence.