BACKGROUND:The sarcopenia index (SI), calculated as the ratio of serum creatinine to cystatin C level, represents skeletal muscle mass and strength. This study aimed to investigate the association between SI and the risk of second hip fractures, considering various demographic and clinical factors to improve second hip fracture risk prediction. METHODS:This prospective cohort study included older adults with low-energy hip fractures who were monitored for at least two years to track the incidence of subsequent hip fractures. Baseline demographic, clinical, and biochemical data were collected. The SI was calculated as serum creatinine [mg/dL]/cystatin C [mg/L]) × 100. Logistic regression models were used to evaluate the relationship between the SI and the risk of a second hip fracture. Subgroup analyses were conducted to assess the effects of potential modifiers, including gender, body mass index, hypertension, diabetes, and estimated glomerular filtration rate. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of SI. RESULTS:A total of 637 patients were included, 59 of whom experienced a second hip fracture during the follow-up period. The patients with second hip fracture exhibited significantly lower SI levels than those without (48.93 ± 8.54 versus 62.95 ± 14.39, P < 0.001). Logistic regression analysis revealed a significant association between a lower muscle-reduction index and an increased risk of a second hip fracture in the fully adjusted model (odds ratio: 0.91; 95% confidence interval: 0.87-0.94; P < 0.001). The area under the ROC curve for predicting a second hip fracture based on the SI was 0.822, indicating good predictive accuracy. Furthermore, subgroup analyses revealed that SI was inversely associated with second hip fracture. CONCLUSIONS:The SI serves as a significant predictor of second hip fractures in older adults, even after considering age, gender, and clinical factors.

BACKGROUND:Sarcopenia index (SI), calculated as serum creatinine/cystatin C × 100, has emerged as a potential marker for muscle loss and adverse outcomes. However, its prognostic value in hip fracture patients remains unclear. This study aimed to investigate the association between SI and all-cause mortality in patients aged 50 and over with hip fracture. METHODS:This study included patients aged 50 and over with low-energy hip fractures and followed them for at least two years to track the incidence of death. Collect baseline demographic, clinical and biochemical data. Kaplan-Meier and log-rank analyses were performed to compare the mortality between different SI levels. Univariate and multivariate cox regression models were used to evaluate the relationship between SI and all-cause mortality in patients aged 50 and over with hip fracture. Subgroup analysis was carried out to evaluate the influence of potential regulators, and cubic spline curves were limited to check the potential nonlinear relationship between SI and all-cause mortality. RESULTS:A total of 637 patients were enrolled in the study, 62 deaths occurred during follow-up. Non-survivors were significantly older (80.02 ± 9.24 vs 71.05 ± 10.75 years, P < 0.001) and had lower SI values (54.06 ± 11.17 vs 61.51 ± 14.51, P < 0.001) compared to survivors. Kaplan-Meier analysis showed significantly better survival in the high SI group (P = 0.0034). In multivariate analysis, SI remained independently associated with mortality after adjusting for comprehensive covariates (HR = 0.98, 95 % CI: 0.95-0.99, P = 0.018). Restricted cubic spline analysis revealed a nearly linear relationship between SI and the risk of death in patients with hip fractures. In subgroup analysis except in diabetes and BMI ≥ 24, SI was negatively correlated with the second hip fracture. CONCLUSIONS:Lower SI values are independently associated with increased all-cause mortality in patients aged 50 and over with hip fracture. SI might serve as a valuable prognostic marker for risk stratification in this population, potentially helping identify high-risk patients who may benefit from more intensive monitoring and intervention.

BACKGROUND:Patients with Type 2 diabetes mellitus (T2DM) have elevated late-night cortisol levels and a flattened circadian rhythm. Cortisol oversecretion mediates muscle breakdown and reduces muscle strength and mass, thus possibly leading to sarcopenia. This study first investigated the association between cortisol circadian rhythm and sarcopenia in patients with T2DM. METHODS:Patients with T2DM and adrenal nodules were screened for eligibility. Skeletal muscle index (SMI) and skeletal muscle density (SMD) were obtained by analysing computed tomography images at Lumbar 3 level. Sarcopenia was defined as the presence of both myopenia and myosteatosis. Cortisol and adrenocorticotropic hormone levels at 8 AM, 4 PM and 0 AM were measured. The cumulative logit models and receiver operating characteristic (ROC) curve analyses were performed to evaluate the association between cortisol circadian rhythm and sarcopenia. RESULTS:In total, 128 patients with T2DM and nonfunctional adrenal adenomas were enrolled in this study, of whom 25 were diagnosed with sarcopenia. The mean age was 54.4 years, and 83 (64.8%) patients were male. Patients with sarcopenia showed higher nighttime cortisol levels at 0 AM (Cor 0 AM) (4.91 [4.05, 9.95] vs. 2.44 [1.55, 4.77] μg/dL, p < 0.001) than those without. The Cor 0 AM was negatively correlated with both SMI and SMD (r = -0.318, p < 0.001 and -0.284, p < 0.001, respectively). As the Cor 0 AM tertiles increased, the odds ratios (ORs) for sarcopenia consistently increased (OR = 4.69 [0.93, 23.53], p = 0.061, for the intermediate group and OR = 11.39 [2.41, 53.84], p = 0.002, for the high group). After adjustment for multiple risk factors, the high Cor 0 AM group still showed a significantly higher risk of sarcopenia than the low group (OR = 7.92 [1.45, 43.29], p = 0.017). ROC curve analyses showed that Cor 0 AM had the highest predictive power for sarcopenia, with an area under the ROC curve (AUC) of 0.760, compared to haemoglobin, age, alanine transaminase and sex (AUC = 0.703, 0.695, 0.679, and 0.633, respectively). CONCLUSIONS:The cortisol circadian rhythm is associated with sarcopenia in patients with T2DM. Patients with higher levels of nighttime cortisol, rather than morning or afternoon cortisol, have a higher risk of sarcopenia. This result offers a new strategy for the further research of sarcopenia.

Low testosterone levels is associated with higher cardiovascular risk in men with diabetes. However, there are few studies on testosterone levels and the factors affecting them in patients with young-onset diabetes (YOD). The objective of this study was to investigate the correlation between waist-to-hip ratio (WHR) and testosterone levels in men diagnosed with YOD. This cross-sectional study involved 547 male patients with type 2 diabetes mellitus (T2DM) from the Endocrinology Department of the Affiliated Hospital of Jining Medical University. The participants were divided into two groups: a young-onset diabetes (YOD) group and a late-onset diabetes (LOD) group. Anthropometric measurements, including height, weight, waist circumference, and hip circumference, were recorded. Additionally, fasting blood samples were collected to assess various parameters, such as sex hormone levels and lipid profiles. The association between WHR and testosterone levels was analyzed by univariate linear regression and multivariable linear regression analysis. Five hundred forty-seven patients with type 2 diabetes and aged 50.3 ± 12.1 years were enrolled in the study. One hundred ninety-three patients were assigned to the YOD group based on a diagnosis age of 40 years or younger, while the remaining 354 patients were assigned to the LOD group. The testosterone was significantly lower in the YOD group compare to the LOD group (P = 0.049), and the WHR had an independent effect on testosterone in men with the YOD group (β=-4.67, P = 0.0251), but there was no evidence of such an association in the LOD group (β =-1.13, P = 0.4608). According to our results, male patients with YOD exhibited lower testosterone levels compared to those with LOD. Furthermore, their testosterone levels were significantly negatively correlated with WHR. These findings indicate that it is more necessary to screen for testosterone in obese patients with YOD and that improving obesity, especially abdominal obesity, may help to interrupt the vicious cycle of low testosterone-obesity-insulin resistance-hyperglycemia-low testosterone.

The signaling pathway of C-type natriuretic peptide (CNP) and its receptor (natriuretic peptide receptor 2, NPR2) is implicated in the process of endochondral ossification, which is crucial for the linear growth of long bones. Loss-of-function mutations in the NPR2 gene cause short stature. This study aimed to identify and characterize truncating mutations in NPR2 among Chinese families with short stature. Whole-exome sequencing and Sanger sequencing were conducted to identify potential mutations. Bioinformatic analysis was utilized to assess the pathogenicity of two mutations. The effects of candidate mutation on gene expression, subcellular localization, protein stability, and protein function were further assessed through in vitro assays. In this study, A novel mutation, c.2629_2630delAG, p.S877Hfs*10 and a previously reported mutation, c.1162 C > T, p.R388* (ClinVar database) in NPR2, were identified in the individuals, and these variants were inherited from the mother and father, respectively. Both mutations were predicted to be deleterious and have a significant impact on protein structure based on bioinformatics analysis. In vitro experiments demonstrated that mutant mRNAs evaded nonsense-mediated mRNA decay (NMD) to produce truncated NPR2 proteins with reduced stability and increased degradation. Furthermore, two truncated NPR2 proteins exhibited impaired localization at the cell membrane and severely reduced ability to stimulate cyclic guanosine monophosphate (cGMP) production in HEK293T cells compared to wild-type (WT) NPR2 (p < 0.05). Our study identified two loss-of-function mutations of the NPR2 gene in two Chinese families and offered new insights on the pathogenesis of short stature caused by NPR2 truncating mutations.

KBG syndrome is a rare autosomal dominant condition characterized by multisystem developmental disorder, primarily caused by loss-of-function variants in ankyrin repeat domain-containing protein 11 (ANKRD11). Approximately 80 % of ANKRD11 variants associated with KBG syndrome, are frameshift and nonsense variants. Current insight into the pathogenesis of KBG syndrome resulting from ANKRD11 truncating variants remains limited. Here, we presented two members from a non-consanguineous Chinese pedigree both exhibiting characteristics fitting the KBG syndrome-associated phenotypic spectrum. Whole-exome sequencing identified a novel heterozygous frameshift variant in ANKRD11 (NM_013275.6, c.2280_2281delGT, p.Y761Qfs*20) in the proband. Sanger sequencing confirmed that the variant was inherited from her mother and co-segregated with KBG syndrome phenotype. In vitro functional assays revealed that the frameshift variant escaped nonsense-mediated mRNA decay, and resulting in a truncated protein with significantly increased expression levels compared to full-length ANKRD11. Immunofluorescence results demonstrated that truncated protein was predominantly expressed in the nucleus of HEK293 cells, while wild-type ANKRD11 was equally distributed in both the nucleus and cytoplasm. Moreover, the truncated protein significantly reduced CDKN1A/P21-promoter luciferase activity in comparison to wild-type ANKRD11 protein, as well as a remarkably decrease in the endogenous CDKN1A/P21 mRNA level in HEK293 cells. These findings suggest a loss of transcriptional activation function and potentially a dominant-negative mechanism. Overall, our study expands the mutational spectrum of ANKRD11 gene and provides new insights into the pathogenic mechanism of KBG syndrome caused by ANKRD11 truncating variants.

Background: Isolated growth hormone deficiency (IGHD) is a rare genetically heterogeneous disorder caused primarily by mutations in GH1 and GH releasing hormone receptor (GHRHR). The aim of this study was to identify the molecular etiology of a Chinese boy with IGHD. Methods: Whole-exome sequencing, sanger sequencing and bioinformatic analysis were performed to screen for candidate mutations. The impacts of candidate mutation on gene expression, intracellular localization and protein function were further evaluated by in vitro assays. Results: A novel heterozygous frameshift mutation in the GHRH gene (c.91dupC, p.R31Pfs*98) was identified in a Chinese boy clinically diagnosed as having IGHD. The mutation was absent in multiple public databases, and considered as deleterious using in silico prediction, conservative analysis and three-dimensional homology modeling. Furthermore, mRNA and protein expression levels of mutant GHRH were significantly increased than wild-type GHRH (p < 0.05). Moreover, mutant GHRH showed an aberrant accumulation within the cytoplasm, and obviously reduced ability to stimulate GH secretion and cAMP accumulation in human GHRHR-expressing pituitary GH3 cells compared to wild-type GHRH (p < 0.05). Conclusion: Our study discovered the first loss-of function mutation of GHRH in a Chinese boy with IGHD and provided new insights on IGHD pathogenesis caused by GHRH haploinsufficiency.

AbstractAnkyrin repeat domain containing-protein 11 (ANKRD11), a transcriptional factor predominantly localized in the cell nucleus, plays a crucial role in the expression regulation of key genes by recruiting chromatin remodelers and interacting with specific transcriptional repressors or activators during numerous biological processes. Its pathogenic variants are strongly linked to the pathogenesis and progression of multisystem disorder known as KBG syndrome. With the widespread application of high-throughput DNA sequencing technologies in clinical medicine, numerous pathogenic variants in the ANKRD11 gene have been reported. Patients with KBG syndrome usually exhibit a broad phenotypic spectrum with a variable degree of severity, even if having identical variants. In addition to distinctive dental, craniofacial and neurodevelopmental abnormalities, patients often present with skeletal anomalies, particularly postnatal short stature. The relationship between ANKRD11 variants and short stature is not well-understood, with limited knowledge regarding its occurrence rate or underlying biological mechanism involved. This review aims to provide an updated analysis of the molecular spectrum associated with ANKRD11 variants, investigate the prevalence of the short stature among patients harboring these variants, evaluate the efficacy of recombinant human growth hormone in treating children with short stature and ANKRD11 variants, and explore the biological mechanisms underlying short stature from both scientific and clinical perspectives. Our investigation indicated that frameshift and nonsense were the most frequent types in 583 pathogenic or likely pathogenic variants identified in the ANKRD11 gene. Among the 245 KBGS patients with height data, approximately 50% displayed short stature. Most patients showed a positive response to rhGH therapy, although the number of patients receiving treatment was limited. ANKRD11 deficiency potentially disrupts longitudinal bone growth by affecting the orderly differentiation of growth plate chondrocytes. Our review offers crucial insights into the association between ANKRD11 variants and short stature and provides valuable guidance for precise clinical diagnosis and treatment of patients with KBG syndrome.

BACKGROUND:Myosteatosis, rather than low muscle mass, is the primary etiologic factor of sarcopenia in patients with type 2 diabetes mellitus (T2DM). Myosteatosis may lead to a series of metabolic dysfunctions, such as insulin resistance, systematic inflammation, and oxidative stress, and all these dysfunctions are closely associated with the acceleration of T2DM and atherosclerosis.AIM:To investigate the association between myosteatosis and coronary artery calcification (CAC) in patients with T2DM.METHODS:Patients with T2DM, who had not experienced major cardiovascular events and had undergone both abdominal and thoracic computed tomography (CT) scans, were included. The mean skeletal muscle attenuation was assessed using abdominal CT images at the L3 level. The CAC score was determined from thoracic CT images using the Agatston scoring method. Myosteatosis was diagnosed according to Martin's criteria. Severe CAC (SCAC) was defined when the CAC score exceeded 300. Logistic regression and decision tree analyses were performed.RESULTS:A total of 652 patients with T2DM were enrolled. Among them, 167 (25.6%) patients had SCAC. Logistic regression analysis demonstrated that myosteatosis, age, duration of diabetes, cigarette smoking, and alcohol consumption were independent risk factors of SCAC. Myosteatosis was significantly associated with an increased risk of SCAC (OR = 2.381, P = 0.003). The association between myosteatosis and SCAC was significant in the younger patients (OR = 2.672, 95%CI: 1.477-4.834, P = 0.002), but not the older patients (OR = 1.456, 95%CI: 0.863-2.455, P = 0.188), and was more prominent in the population with lower risks of atherosclerosis. The decision tree analyses prioritized older age as the primary variable for SCAC. In older patients, cigarette smoking was the main contributing factor for SCAC, while in younger patients, it was myosteatosis.CONCLUSION:Myosteatosis is a novel risk factor for atherosclerosis in patients with T2DM, especially in the population with younger ages and fewer traditional risk factors.

The clinical data of a patient with mitochondrial diabetes mellitus complicated with hypopituitarism were analyzed, the patient′s mitochondrial gene was detected by microarray capture high-throughput sequencing, and the related domestic and foreign literature was reviewed and analyzed. The results showed that the patient had m. 3243 A>G variant on MT-TL1 gene and the clinical features were consistent with mitochondrial diabetes mellitus and hypopituitarism.

近年来，糖尿病的发病率在世界范围内不断上升，有关糖尿病及其并发症的防治已成为医学研究的热门话题，骨质疏松症是糖尿病最常见的并发症之一，与糖尿病患者的生存质量密切相关。本文就体重指数、血糖、尿酸、肌酐、胱抑素C等影响2型糖尿病患者骨密度的危险因素及其可能的发病机制进行分析阐述。旨在为临床医生深入了解糖尿病患者的骨骼健康问题提供新思路，为临床诊疗这类疾病提供新方法。

BackgroundSince the triglyceride glucose (TyG) index can reflect insulin resistance, it has been proven to be an efficient predictor of glycolipid-metabolism-related diseases. Therefore, this study aimed to investigate the predictive value of the TyG index for visceral obesity (VO) and body fat distribution in patients with type 2 diabetes mellitus (T2DM).MethodsAbdominal adipose tissue characteristics in patients with T2DM, including visceral adipose area (VAA), subcutaneous adipose area (SAA), VAA-to-SAA ratio (VSR), visceral adipose density (VAD), and subcutaneous adipose density (SAD), were obtained through analyses of computed tomography images at the lumbar 2/3 level. VO was diagnosed according to the VAA (> 142 cm(2) for males and > 115 cm(2) for females). Logistic regression was performed to identify independent factors of VO, and receiver operating characteristic (ROC) curves were used to compare the diagnostic performance according to the area under the ROC curve (AUC).ResultsA total of 976 patients were included in this study. VO patients showed significantly higher TyG values than non-VO patients in males (9.74 vs. 8.88) and females (9.59 vs. 9.01). The TyG index showed significant positive correlations with VAA, SAA, and VSR and negative correlations with VAD and SAD. The TyG index was an independent factor for VO in both males (odds ratio [OR] = 2.997) and females (OR = 2.233). The TyG index ranked second to body mass index (BMI) for predicting VO in male (AUC = 0.770) and female patients (AUC = 0.720). Patients with higher BMI and TyG index values showed a significantly higher risk of VO than the other patients. TyG-BMI, the combination index of TyG and BMI, showed significantly higher predictive power than BMI for VO in male patients (AUC = 0.879 and 0.835, respectively) but showed no significance when compared with BMI in female patients (AUC = 0.865 and 0.835, respectively).Conclusions. TyG is a comprehensive indicator of adipose volume, density, and distribution in patients with T2DM and is a valuable predictor for VO in combination with anthropometric indices, such as BMI.

Purpose: Genetic factors account for a large proportion of idiopathic hypogonadotropic hypogonadism (IHH) etiologies, although not necessarily a complete genetic basis. This study aimed to characterize the clinical presentations, genetic variants, and therapeutic outcomes of patients with sporadic IHH, which may be helpful for genetic counseling and treatment decisions.Patients and Methods: Eleven Chinese patients with IHH were retrospectively analyzed. Rare genetic variants were evaluated using whole-exome sequencing and bioinformatics analysis and were further classified according to the ACMG-AMP guidelines. The therapeutic responses of patients were further evaluated.Results: Six heterozygous variants of SOX10, WDR11, PROKR2, CHD7 and FGF17 were detected in five Kallmann syndrome (KS) patients, whereas two heterozygous variants of CHD7 and PROKR2 were detected in two normosmic IHH (nIHH) patients. Among these variants, a novel likely pathogenic variant in the SOX10 (c.429-1G>C) was considered to cause the KS phenotype in patient 02, and two potential variants of uncertain significance (VUS) in CHD7 (c.3344G>A and c.7391A>G) possibly contributed to the KS phenotype in patient 05 and the nIHH phenotype in patient 07, which need to be confirmed by further evidence. Additionally, long-term testosterone or estradiol replacement treatment effectively improved the development of sexual characteristics in patients with IHH.Conclusion: Next-generation sequencing is a powerful tool for identifying the molecular etiology and early diagnosis of IHH. Efficient therapeutic outcomes strongly indicate a need for timely treatment.

Objective:To investigate the predictive power of basal luteinizing hormone (LH) level for central gonadal activation states in girls.Methods:A total of 343 girls who developed secondary sex characteristics before the age of 8 years old and were hospitalized in the Affiliated Hospital of Jining Medical University from February 2015 to August 2022 were included in this study. The general clinical data were collected and the gonadotropin-releasing hormone analogue (GnRHa) stimulation test was performed. Based on the peak of LH in the GnRHa stimulation test, these girls were categorized into three groups: premature thelarche (PT), partial central precocious puberty (CPP), and complete CPP. The Logistic regression was used to clarify the independent correlation factors of PT and complete CPP. Receiver operating characteristic (ROC) curve was applied to compare the predictive power of the independent factors for PT and complete CPP.Results:Basal LH level showed significant differences between PT, partial CPP, and complete CPP groups with quartiles of 0.06(0.01, 0.16)U/L, 0.30(0.12, 0.56)U/L, and 1.50(0.72, 2.83)U/L, respectively. The difference between the three groups was meaningful in statistic (H=164.74, P<0.01). Age, basal LH, estradiol level, and uterine volume were independent influential factors of PT. Basal LH, estradiol level, and uterine volume were independent influential factors for complete CPP. Basal LH level was the best predictor for PT and complete CPP with AUCs of 0.874 and 0.878, respectively. The optimal cut-points of basal LH level for predicting PT and complete CPP were 0.185 U/L (sensitivity 83.90%, specificity 75.90%) and 0.435 U/L (sensitivity 80.50%, specificity 84.10%), respectively.Conclusion:Basal LH level is a valuable predictor of central gonadal activation states in girls, and can be used as an early screening index for CPP.

患者 女，12岁，因身材矮小就诊。患者系孕40周顺产，出生体重3.25 kg，身长不详，因缺氧住院治疗3天，Apgar评分不详。走、爬时间较晚，8个月出牙，3岁会说话、独立行走，平素运动协调差，不能独立完成跳绳等运动，学习成绩差。自幼身高增长缓慢，视力欠佳，半月前月经初潮，近1年身高增长约7 cm。查体：身高131.7 cm(< 第3百分位)，体重31 kg，圆脸，脸颊饱满，面部多痣，睑下垂，低耳位，短人中，嘴角向下，小下颌，牙齿不整齐，双乳Tanner分期Ⅱ ~ Ⅲ期，无腋毛，阴毛Tanner分期Ⅰ期，心肺查体未见明显异常，双手远端指间关节屈曲。生化及影像学检查：骨龄约12岁；性激素：雌二醇74.39 pg/mL，促黄体生成素3.56 mIU/mL，卵泡刺激素4.33 mIU/mL；生长激素峰值5.44 ng/mL；IGF-1 361 ng/mL，其余生化及影像学检查均未见异常。患儿染色体核型为46，XX。全外显子测序结果为46，XN，del(8q21.11-q21.12-q21.13)．seq[GRCh37/hg19](77 188 701-82 355 132)×1即8q21.11-q21.13区存在5.17 Mb的杂合缺失，其父母未发现相同变异。拷贝数变异测序(copy number variation sequencing，CNV-Seq)结果为chr8：g.77 183 731-82 378 196del，证实存在5.19 Mb片段缺失，ClinGen CNV评分≥ 0.99，提示为致病性，缺失区涉及 ZFHX4、PEX2、PKIA、IL7、STMN2等15个蛋白质编码基因(图1)。

AIMS:Glucagon‑like peptide 1 receptor agonist (GLP-1RA) treatment can improve adipose distribution. We performed this meta-analysis to investigate whether GLP-1RAs preferentially reduce visceral adipose tissue (VAT) over subcutaneous adipose tissue (SAT) in patients with type 2 diabetes.MATERIALS AND METHODS:We searched MEDLINE and the Cochrane Library for randomised controlled trials explicitly reporting changes in VAT and SAT. A random-effects model was performed to estimate the weighted mean difference (MD) for VAT and SAT. Heterogeneity among the studies was assessed using I2 statistics, and publication bias was assessed using Egger's tests. Meta-regression was performed to identify the correlation between changes in adipose tissues and changes in body weight and glycated haemoglobin level.RESULTS:Ten trials with 924 patients were enrolled in the meta-analysis. GLP-1RA treatment led to similar absolute area (cm2) reductions in VAT (MD -21.13 cm2, 95% CI [-29.82, -12.44]) and SAT (MD -22.89 cm2, 95% CI [-29.83, -15.95]). No significant publication bias was detected, and this result was stable in the sensitivity and subgroup analyses. Moreover, GLP-1RA treatment resulted in a greater reduction in VAT and SAT in the subgroup with a greater reduction in body weight. The absolute area reduction in VAT was significantly correlated with the reduction in body weight (r = 6.324, p = 0.035).CONCLUSIONS:GLP-1RA treatment leads to significant and similar absolute reductions in VAT and SAT, and the reduction in adipose tissues may be correlated with the reduction in body weight.

Objective To evaluate the association between the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis and muscle density in children and adolescents of short stature. Methods Participants were children and adolescents of short stature hospitalized in the Affiliated Hospital of Jining Medical University between January 2020 and June 2021. All participants had CT scan images available. We performed an analysis of the images to calculate the muscle density or skeletal muscle attenuation (SMA), skeletal muscle index (SMI), and fat mass index (FMI). Bioelectrical impedance analysis (BIA) was used to ensure that chest CT is a credible way of evaluating body composition. Results A total of 297 subjects were included with the mean age of 10.00 ± 3.42 years, mean height standard deviation score (SDS) of -2.51 ± 0.53, and mean IGF-1 SDS of -0.60 ± 1.07. The areas of muscle and fat tissues at the fourth thoracic vertebra level in the CT images showed strong correlation with the total weights of the participants (R2 = 0.884 and 0.897, respectively). The peak of GH was negatively associated with FMI (r = - 0.323, P <.01) and IGF-1 SDS was positively associated with SMI (r = 0.303, P <.01). Both the peak GH and IGF-1 SDS were positively associated with SMA (r = 0.244, P <.01 and r = 0.165, P <.05, respectively). Multiple stepwise linear regression analysis demonstrated that the GH peak was the predictor of FMI (β = - 0.210, P < .01), the IGF-1 SDS was the predictor of SMI (β = 0.224, P < .01), and both the peak GH and IGF-1 SDS were predictors of SMA (β = 0.180, P < .01 and β = 0.222, P < .01). Conclusions A chest CT scan is a credible method of evaluating body composition in children and adolescents of short stature. In these patients, peak GH and IGF-1 SDS are independent predictors of muscle density and the GF/IGF-1 axis may regulate body composition through complex mechanisms.

Objective: This study aims to explore the risk signals of osteonecrosis of the jaw induced by antiresorptive drugs and provide references for the clinical safety application.Method: According to the FDA’s Adverse Event Reporting System (FAERS), from January 2004 to September 2021, we chose “Osteonecrosis of the jaw (10064658)” and “Exposed bone in jaw (10071014)” as preferred terms, “antiresorptive drugs” as the target drugs, and primary suspect drug as the drug role code in the dataset. We evaluated the association between drugs and adverse events by using reporting odds ratio (ROR) based on disproportionality analysis. We took the High-Level Terms (HLT) of MedDRA® as the classification level of indications to calculate ROR to compare the signal difference of ONJ in different indications. In addition, patients with antiresorptive-induced osteonecrosis of the jaw and the time of onset of the condition following different antiresorptive medications were collected for the study.Results: The FAERS contained 18,421 reports relating to jaw osteonecrosis from January 2004 to September 2021. A total of eight antiresorptive agents were included in the analysis. From high to low, the ROR of ONJ induced by antiresorptive agents (regardless of indication) is pamidronate (ROR = 494.8), zoledronic acid (ROR = 431.9), denosumab (ROR = 194.8), alendronate (ROR = 151.2), risedronate (ROR = 140.2), etidronic acid (ROR = 64.5), ibandronate (ROR = 40.8), and romosozumab (ROR = 6.4). HLT ROR values for “metabolic bone disorders” were the lowest for each drug, while HLT ROR values were high for “tumor-related indications,” including breast and nipple neoplasms malignant, plasma cell myelomas, and prostatic neoplasms malignant. The onset time for osteonecrosis of the jaw as median (Q1, Q3), osteoporosis-related indications, and the onset time for ONJ were 730 (368, 1268), 489.5 (236.3, 909.8), 722.5 (314, 1055), 761 (368, 1720), and 153 (50, 346) for zoledronic acid, denosumab, ibandronate, risedronate, and romosozumab, respectively. Cancer-related indications: the onset time for ONJ were 680.5 (255.3, 1283), 488 (245, 851), and 696.5 (347, 1087) for zoledronic acid, denosumab, and pamidronate, respectively.Conclusion: When antiresorptive drugs are used for metastasis, they have the largest risk signal, followed by malignancy, and the smallest is osteoporosis. The onset time of ONJ may not be related to the indications. The onset time of ONJ for BPs was about 2 years, denosumab about 1.3 years, and romosozumab less than 1 year, which may be related to sequential treatment. When used according to the instructions, the risk of ONJ caused by denosumab was higher than that of zoledronic acid, regardless of the indication. Based on these findings, researchers will continue to monitor and identify risk factors.

Abstract This study aimed to investigate the relationship between body composition and the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis in children and adolescents with short stature. All participants underwent a bioelectrical impedance analysis (BIA) and growth hormone stimulation tests, and their percentage of body fat (PBF), fat mass index (FMI), free fat mass index (FFMI), and skeletal muscle index (SMI) were calculated. The study included 310 individuals aged 10.19 ± 3.24 years, with height standard deviation score (SDS) of − 2.44 ± 0.56 and the mean peak of GH was 7.20 ± 5.11 ng/mL. Pearson analysis demonstrated that peak GH value negatively correlated with PBF and FMI. Contrastingly, IGF-1 SDS was positively correlated with FFMI and SMI. Multiple linear regression analysis showed that GH peak and IGF-1 SDS were independent predictors of PBF/FMI and FFMI/SMI, respectively. Serum GH and IGF-1 SDS were associated with body fat and lean body weight, respectively.