Frontiers in Endocrinology最新文献

{"title":"Hypertriglyceridemic waist-to-height ratio and the triple burden of hypertension, diabetes, and dyslipidemia in adults: association and network analysis.","authors":"Lanqiqi Wu, Jiaoyang Chen, Ting He, Ling Ma, Yin Cheng, Yining Liu, Jinyu Ma, Huitian Tong, Chao Shi","doi":"10.3389/fendo.2026.1932657","DOIUrl":"10.3389/fendo.2026.1932657","url":null,"abstract":"<p><strong>Background: </strong>Hypertension, diabetes, and dyslipidemia frequently co-occur, yet simple screening tools are lacking in resource-limited settings. The hypertriglyceridemic waist-to-height ratio (HTH/WH) phenotype has emerged as a potential indicator, but its utility for identifying the triple burden of hypertension, diabetes, and dyslipidemia remains underexplored, particularly in underdeveloped regions of China.</p><p><strong>Methods: </strong>This cross-sectional study included 10,796 adults (≥18 years) from the Ningxia Hui Autonomous Region, Northwest China. The HTH/WH phenotype was defined as triglycerides ≥1.7 mmol/L combined with waist-to-height ratio ≥0.5. Multivariable logistic regression was used to estimate adjusted odds ratios (ORs) for the association between the HTH/WH phenotype and coexisting hypertension, diabetes, and dyslipidemia. Mixed graphical models were employed to characterize the network associations among the HTH/WH phenotype, the three cardiometabolic disorders, and modifiable lifestyle factors.</p><p><strong>Results: </strong>The prevalence of concurrent hypertension, diabetes, and dyslipidemia was 3.99% in Ningxia, exceeding the Northwest China regional average of 2.33%. The HTH/WH phenotype was present in 21.30% of the population and demonstrated a significant, dose-response association with the triple burden (adjusted OR = 5.29, 95% CI: 4.14-6.74), as well as with two diseases (adjusted OR = 5.12, 95% CI: 4.22-6.21) and one disease (adjusted OR = 1.97, 95% CI: 1.77-2.20). Factors independently associated with the triple burden included age ≥40 years, smoking, alcohol consumption, and elevated BMI (≥24 kg/m²), while higher education and married status were inversely protective. Mixed graphical modeling revealed the HTH/WH phenotype as a central bridge node (bridge strength = 0.67) within the metabolic disorder network, with strong direct connections to hypertension, diabetes, and dyslipidemia. BMI exhibited the highest bridge centrality (bridge strength = 1.72), followed by smoking (bridge strength = 0.32).</p><p><strong>Conclusions: </strong>In Ningxia Hui Autonomous Region, concurrent hypertension, diabetes, and dyslipidemia pose a substantial health burden among adults. The HTH/WH phenotype may serve as a practical risk assessment indicator for identifying high-risk individuals with this metabolic multimorbidity.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1932657"},"PeriodicalIF":5.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13683101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of preimplantation genetic testing for aneuploidy in improving pregnancy outcome among couples with azoospermia: study protocol for a multicenter, randomized controlled trial.","authors":"Yaqiong He, Jiaan Huang, Junhao Yan, Jichun Tan, Zhe Wei, Yun Sun, Yao Lu","doi":"10.3389/fendo.2026.1903245","DOIUrl":"10.3389/fendo.2026.1903245","url":null,"abstract":"<p><strong>Background: </strong>Azoospermia affects up to one in ten infertile couples and represents one of the most challenging conditions in male infertility. Although the development of intracytoplasmic sperm injection (ICSI) enables azoospermic men to achieve biological parenthood, overall success rates remain modest. Preimplantation genetic testing for aneuploidy (PGT-A) is increasingly promoted and used worldwide to improve pregnancy outcomes and enhance the efficiency of ICSI; however, its efficacy for couples with azoospermia remains uncertain. Robust evidence from adequately powered randomized controlled trials (RCTs) is still lacking to determine whether PGT-A can increase the live birth rate as the primary outcome in this context.</p><p><strong>Methods: </strong>This trial is designed as a prospective, multicenter, open-label RCT. Couples with azoospermia (female age 20-37 years; male age 20-55 years) who intend to undergo ICSI with partner's sperm will be screened for eligibility. Women who have at least two blastocysts available on day 5 of embryo culture will be enrolled and randomly assigned in a 1:1 ratio to receive either PGT-A or conventional ICSI. A freeze-all strategy with single frozen-thawed blastocyst transfer will be implemented in both groups. The primary outcome is live birth rate.</p><p><strong>Discussion: </strong>The findings of this trial are expected to provide high-quality evidence regarding the efficacy of PGT-A for couples with azoospermia, helping optimize individualized patient management and improve overall treatment efficiency.</p><p><strong>Clinical trial registration: </strong>http://www.chictr.org.cn/, identifier ChiCTR2100043421.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1903245"},"PeriodicalIF":5.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First-morning urinary luteinizing hormone and bone age decomposition for diagnosis of central precocious puberty in girls: a two-step prediction model study.","authors":"Miao Huang, Xiyan Lu, Peipei Liu, Guoqing Dong, Mingzhu Li, Wujin Wang, Jianxu Li","doi":"10.3389/fendo.2026.1948363","DOIUrl":"https://doi.org/10.3389/fendo.2026.1948363","url":null,"abstract":"<p><strong>Objective: </strong>The diagnosis of central precocious puberty (CPP) in girls relies on the invasive gonadotropin-releasing hormone (GnRH) stimulation test. Urinary luteinizing hormone (LH) is a noninvasive candidate biomarker, but evidence from Chinese populations and its integration into multivariable prediction frameworks remain limited. We evaluated the diagnostic accuracy of first-morning urinary LH for CPP, established sex- and pubertal stage-specific reference intervals, and developed a two-step prediction model based on a bone age decomposition.</p><p><strong>Methods: </strong>In this single-center retrospective diagnostic accuracy study, we enrolled 808 children: 295 girls with early breast development (146 CPP, 149 non-CPP), 271 healthy girls, and 242 healthy boys (reference intervals only). First-morning urine was assayed for LH, follicle-stimulating hormone (FSH), and creatinine. Diagnostic performance was evaluated primarily in the 295 symptomatic girls, with an extended analysis in 566 girls including healthy controls; multivariable logistic regression decomposed bone age into chronological age (CA) and the BA-CA difference as separate predictors.</p><p><strong>Results: </strong>Urinary LH showed moderate accuracy for CPP in the primary symptomatic cohort (AUC 0.692, 95% CI 0.630-0.752), peaking in girls aged 7-8 years (AUC 0.708, 95% CI 0.621-0.785); the extended cohort gave similar results (AUC 0.712; secondary, spectrum-extended estimate). The LH-to-creatinine ratio offered no improvement. Basal serum LH was the superior single marker (AUC 0.868 vs 0.692, P < 0.001). The noninvasive Model 1 (CA + BA-CA + urinary LH + breast Tanner stage + uterine length) achieved a C-statistic of 0.853 (sensitivity 73.3%, specificity 83.2%), with CA, BA-CA, and urinary LH as independent predictors. Adding basal serum LH and FSH (Model 2) improved the C-statistic to 0.909; urinary LH retained independent significance (aOR 1.280, P = 0.024), whereas basal FSH was inversely associated with CPP. Bootstrap-corrected C-statistics were 0.838 (Model 1) and 0.893 (Model 2). Pubertal-onset cutoffs were >1.02 mIU/mL in girls and >0.95 mIU/mL in boys.</p><p><strong>Conclusions: </strong>Decomposing bone age into CA and BA-CA enables tiered CPP risk stratification: the noninvasive model supports initial screening without blood sampling, and the complete model refines risk once serum gonadotropins become available. Urinary LH is a clinically useful component of tiered diagnostic algorithms for CPP.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1948363"},"PeriodicalIF":5.7,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13686030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149243923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex, BMI, skeletal maturation, and height among children and adolescents in high-altitude Xizang: a cross-sectional study.","authors":"Lihui Yang, Xiaoyong Yuan, Xiaolong Wu, Shuyou Meng, Xuemei Lv, Zhining Zhang","doi":"10.3389/fendo.2026.1942630","DOIUrl":"10.3389/fendo.2026.1942630","url":null,"abstract":"<p><strong>Background: </strong>Skeletal maturation influences the interpretation of childhood height, but its relationship with sex, body mass index (BMI), and attained height in children living at high altitude remains incompletely characterized. We examined concurrent associations among sex, BMI, bone-age deviation, and height relative to national reference values in children and adolescents living in Lhasa, Xizang.</p><p><strong>Methods: </strong>This cross-sectional study included 199 participants aged 3-16 years (101 girls and 98 boys). Bone-age deviation was defined as bone age minus chronological age. Height difference and BMI difference were calculated relative to age- and sex-specific national reference values. Multivariable linear regression incorporated centered chronological age and its quadratic term, ethnicity, BMI difference, and pubertal status, with HC3 heteroscedasticity-consistent standard errors. Statistical indirect associations through bone-age deviation were estimated using 5,000 participant-level bootstrap resamples.</p><p><strong>Results: </strong>Mean bone-age deviation was -0.64 ± 1.14 years. After adjustment, boys had a 0.65-year lower bone-age deviation than girls (95% CI, -0.96 to -0.33; P < 0.001). Each 1-kg/m² increase in BMI difference was associated with a 0.06-year increase in bone-age deviation (95% CI, 0.01 to 0.10; P = 0.010). Each 1-year increase in bone-age deviation was associated with a 2.76-cm greater height difference from the national reference (95% CI, 1.82 to 3.70; P < 0.001). The sex-related statistical indirect association through bone-age deviation was -1.78 cm (percentile 95% CI, -2.89 to -0.83; BCa 95% CI, -3.02 to -0.90). The corresponding direct association had confidence intervals spanning zero. Principal findings were generally retained in sensitivity analyses using grouped Tanner stages and after exclusion of influential or extreme observations.</p><p><strong>Conclusion: </strong>In this Lhasa sample, boys showed greater skeletal maturation delay than girls, and skeletal maturity was strongly associated with current height relative to national references. Higher BMI relative to the corresponding reference was associated with more advanced skeletal maturation. These cross-sectional findings describe statistical associations and do not establish temporal mediation or an altitude-specific causal effect.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1942630"},"PeriodicalIF":5.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13680247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149230975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diabetes duration modifies the association between AIP and MAFLD in type 2 diabetes.","authors":"Jiayu Ma, Xiaokang Hu, Xiaohe Liang, Kangtao Jin","doi":"10.3389/fendo.2026.1952511","DOIUrl":"10.3389/fendo.2026.1952511","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated fatty liver disease (MAFLD) is highly prevalent in patients with type 2 diabetes mellitus (T2DM). Although several insulin resistance (IR)-related indices have been proposed as surrogate markers, their comparative performance and the influence of diabetes duration remain unclear. We compared the associations of eight IR-related indices with MAFLD and evaluated the modifying effect of diabetes duration.</p><p><strong>Methods: </strong>This retrospective cross-sectional study included 5,996 patients with T2DM, of whom 3,087 had MAFLD. Logistic regression was used to evaluate the associations of eight IR-related indices (TyG, TyG-BMI, METS-IR, CHG, CTI, HOMA-IR, SHR, and AIP) with prevalent MAFLD. To facilitate comparison across indices measured on different scales, odds ratios (ORs) were additionally estimated per 1-standard deviation (SD) increase. Receiver operating characteristic (ROC) curve analysis was used to assess discriminative performance. LASSO regression was used for covariate selection, followed by multivariable logistic regression, restricted cubic spline (RCS) analysis, and interaction analysis. Internal validation of the multivariable model was performed using 1,000 bootstrap resamples.</p><p><strong>Results: </strong>All eight IR-related indices were significantly associated with prevalent MAFLD. After standardization, AIP showed the largest association estimate per 1-SD increase (OR = 2.137, 95% CI: 2.007-2.275). AIP also showed the highest, although moderate, discriminative performance among the eight indices (AUC = 0.692). After LASSO-based covariate selection and multivariable adjustment, AIP remained independently associated with prevalent MAFLD (OR = 4.968, 95% CI: 4.100-6.035). Adjusted RCS analysis indicated a nonlinear association between AIP and prevalent MAFLD (P for overall < 0.001; P for nonlinearity = 0.040). The revised multivariable model had an apparent AUC of 0.758 (95% CI: 0.746-0.771), with an optimism-corrected AUC of 0.756 after bootstrap internal validation. Significant interactions were observed between AIP and diabetes duration when duration was modeled continuously (P for interaction = 0.031) and categorically (<5 vs. ≥5 years; P for interaction = 0.001).</p><p><strong>Conclusions: </strong>Among the eight IR-related indices evaluated, AIP showed the largest standardized association with prevalent MAFLD and the highest discriminative performance in patients with T2DM. The association between AIP and MAFLD may vary according to diabetes duration.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1952511"},"PeriodicalIF":5.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13680141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149231034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Cardiovascular-kidney-metabolic health, genetic susceptibility, and incident cancer risk: a prospective UK biobank cohort and machine learning study.","authors":"Xue He, Junqiao An, Chunjia Yan, Yutong Zhou, Ziyan Wu, Mengyao Xu, Qingyong He","doi":"10.3389/fendo.2026.2006958","DOIUrl":"https://doi.org/10.3389/fendo.2026.2006958","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fendo.2026.1884752.].</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"2006958"},"PeriodicalIF":5.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular signaling networks that connect tissue dysfunction to systemic insulin resistance.","authors":"Rashid Mir, Naseh A Algehainy, Mohammed M Jalal, Malik A Altayar, Reema M Almotairi, Faris J Tayeb, Ruqaiah I Bedaiwi, Faisal H Altemani, Kholoud S Almasoudi, Ibrahim Altedlawi Albalawi, Imadeldin Elfaki","doi":"10.3389/fendo.2026.1952238","DOIUrl":"https://doi.org/10.3389/fendo.2026.1952238","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Insulin resistance is conventionally described as a single condition, but it is better understood as the point at which several tissue-specific signaling failures, each following its own molecular logic and its own timeline, converge into one measurable phenotype. This review treats insulin resistance as a network rather than a collection of independent organ pathologies. Because the components of this network rest on very different kinds of evidence, each node and edge is graded explicitly by study design and causal status, and the time-staged sequence is presented as a falsifiable proposal rather than an established progression. Put simply, insulin resistance is treated here not as one defect but as the shared endpoint of several tissue-specific failures that develop at different times and communicate with one another. Liver, skeletal muscle, adipose tissue, pancreatic islets, the gut, and the brain are each examined as nodes with characteristic signaling lesions built from a shared architecture of diacylglycerol- and ceramide-activated kinases, inhibitory serine phosphorylation of insulin receptor substrate proteins, and endoplasmic reticulum stress, while inter-organ messengers, incretins, adipokines, bile acids, and autonomic circuits, are treated as the edges that couple these nodes together. The pancreas is included not as a site of resistance but as the network's compensatory arm, and the brain is treated as an integrated hypothalamic-vagal node rather than a separate neurocognitive topic, closing a loop in which adipose-derived signals impair central insulin and leptin action, weakened central signaling relaxes hepatic glucose control, and reduced satiety sustains the intake that drove adipose dysfunction in the first place. A dedicated section addresses the post-translational and organelle-level machinery, shared serine kinases, ubiquitin-mediated IRS degradation, O-GlcNAcylation, and mitochondria-endoplasmic reticulum contact sites, that allows the same small set of molecular tools to produce different tissue-specific outputs. These mechanisms are then placed on an explicit time axis moving from silent compensation, in which adipose and hypothalamic changes precede any measurable defect elsewhere, through early decompensation in liver and muscle, to established decompensation marked by β-cell failure and self-sustaining feed-forward loops, a staging distinction that is largely absent from mechanistic studies conducted at a single, typically late, disease stage. This framing helps explain a pattern in current therapeutics: interventions that act on several network nodes at once, most notably incretin-based therapies, have outperformed mechanistically well-motivated single-node strategies, including direct inhibition of shared convergence kinases. The review closes by identifying where the network remains least understood, principally in longitudinal, tissue-resolved human data capable of testing the proposed staging sequence direc","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1952238"},"PeriodicalIF":5.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diagnostic value of saline infusion test-derived biochemical parameters for primary aldosteronism subtyping.","authors":"Yusuf Öztürk, Feridun Karakurt","doi":"10.3389/fendo.2026.1923356","DOIUrl":"10.3389/fendo.2026.1923356","url":null,"abstract":"<p><strong>Background: </strong>Current clinical practice guidelines recommend adrenal venous sampling (AVS) for subtype classification in patients with primary aldosteronism (PA) who are candidates for adrenalectomy; however, AVS may be considered unnecessary in selected young patients with a high probability of unilateral disease. The additional diagnostic information provided by baseline and saline infusion test (SIT)-derived biochemical parameters when evaluated alongside clinical and radiological features remains uncertain. We aimed to compare the diagnostic performance of baseline and SIT-derived biochemical parameters for predicting unilateral PA and to evaluate the additional diagnostic information provided by each parameter when individually added to a common clinical-radiological framework.</p><p><strong>Methods: </strong>This retrospective study included 73 patients with PA (41 unilateral and 32 bilateral) who underwent successful AVS for subtype classification. Baseline plasma aldosterone concentration (PAC), baseline aldosterone-to-potassium ratio (APR), post-SIT PAC, SIT-derived APR, and the suppression index were evaluated. Diagnostic performance was assessed using receiver operating characteristic (ROC) curve analysis, while their associations within a common clinical-radiological model were evaluated using multivariable logistic regression analysis.</p><p><strong>Results: </strong>Post-SIT PAC and SIT-derived APR showed the highest numerical discriminative performance among the evaluated biochemical parameters for predicting unilateral PA (AUC = 0.817 and 0.837, respectively). Adding either parameter individually to the common clinical-radiological model significantly improved model fit (likelihood-ratio <i>p</i> = 0.014 and <i>p</i> = 0.028, respectively); however, the increases in AUC were not statistically significant (ΔAUC = 0.022, <i>p</i> = 0.185 and ΔAUC = 0.017, <i>p</i> = 0.107, respectively). Post-SIT PAC and SIT-derived APR were strongly correlated (Spearman's ρ = 0.983, <i>p</i> < 0.001), and their ROC-derived thresholds yielded concordant classifications in 97.3% of patients.</p><p><strong>Conclusion: </strong>Our findings suggest that post-SIT PAC shows useful discriminative performance for predicting unilateral PA and may contribute to subtype assessment when considered alongside clinical and radiological features. These findings require validation in independent cohorts.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1923356"},"PeriodicalIF":5.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13680153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149231037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retinoic acid signaling in growth plate development: receptor-specific effects, antagonist evidence, and pediatric translational considerations.","authors":"Yutong Xing, Ruiying Fan, Kaixi Wang, Xinyu Ma, Fan Xuan, Huifeng Zhang","doi":"10.3389/fendo.2026.1962290","DOIUrl":"https://doi.org/10.3389/fendo.2026.1962290","url":null,"abstract":"<p><p>The growth plate is a spatially organized cartilage structure that drives longitudinal bone growth and is particularly vulnerable to nutritional imbalance, systemic disease, trauma, and drug exposure during childhood. Retinoic acid (RA), the bioactive metabolite of vitamin A, regulates transcription through retinoic acid receptors (RARα, RARβ, and RARγ). Its skeletal effects depend on concentration, developmental timing, tissue context, and receptor subtype. Physiologic RA homeostasis contributes to orderly chondrocyte maturation, whereas excessive or spatially inappropriate signaling can suppress proliferation, alter hypertrophic differentiation and extracellular matrix, and promote premature growth plate senescence or closure in experimental models. This narrative review integrates evidence on RA metabolism, RAR-dependent chondrocyte fate, and experimental RAR antagonists. Model-dependent antagonist effects include concurrent prevention of hedgehog inhibitor-associated closure and early post-injury attenuation of growth inhibition in juvenile mice; prevention during induction is not reversal of established physeal damage. Human zone-specific receptor biology remains insufficiently resolved, and apparently conflicting findings reflect differences in receptor pharmacology, tissue, developmental stage, timing, dose, and endpoint. Pediatric experience with systemic retinoids, including isotretinoin and the RARγ agonist palovarotene, underscores the developmental hazards of pathway modulation. Future studies should prioritize validated human growth plate models, receptor-subtype pharmacology, and longitudinal skeletal monitoring. RAR antagonism remains a preclinical, hypothesis-generating strategy requiring rigorous dose-window and long-term safety evaluation before pediatric clinical investigation.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1962290"},"PeriodicalIF":5.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Cortical bone loss, impaired mineralization, and reduced adiposity contributing to chronic bone pain in SFRP4-related skeletal disease with an ALPL variant.","authors":"Fernando Lizcano, Eliana Avilés, Cristian López, Silvia Maradei-Anaya, Maria Camila Ballesteros-García, Lizeth Bustamante, Fredy Luna, Miguel O'Meara, Alex Valenzuela","doi":"10.3389/fendo.2026.1971751","DOIUrl":"https://doi.org/10.3389/fendo.2026.1971751","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fendo.2026.1870802.].</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1971751"},"PeriodicalIF":5.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}