Frontiers in Endocrinology最新文献

{"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":"Early changes in the central vision and the macula in diabetic retinal disease: associations with serum biomarkers.","authors":"Norihiro Nagai, Hajime Shinoda, Shu Meguro, Shozo Sonoda, Taiji Sakamoto, Kazuno Negishi, Yoko Ozawa","doi":"10.3389/fendo.2026.1972307","DOIUrl":"https://doi.org/10.3389/fendo.2026.1972307","url":null,"abstract":"<p><strong>Background: </strong>Recent progress in medical science allows patients with diabetes to expect preservation of good central vision. However, the influence of diabetes-related systemic factors on the macula is not fully understood. We therefore investigated associations among central vision, macular neural and vascular parameters, and systemic biomarkers to explore the pathogenesis of early diabetic retinal disease (DRD).</p><p><strong>Methods: </strong>In this retrospective observational study, we evaluated best-corrected visual acuity (BCVA), size parameters of components of the neural retina, and blood flow in the retina and choroid in patients with diabetes and no obvious macular lesions. Optical coherence tomography (OCT) and OCT angiography (OCTA) were used for the ocular assessments. Serum biomarker levels were determined from routine blood tests. Associations among ocular parameters and between ocular parameters and serum biomarkers were analyzed using Spearman's rank correlation coefficient analyses and multiple regression analyses adjusted for age, sex and duration of diabetes.</p><p><strong>Results: </strong>The study included 121 eyes of 121 patients (mean age, 61.7 years), of whom 80 (66.1%) were male. In analyses adjusted for age, sex and duration of diabetes, worse BCVA was associated with shorter photoreceptor outer segment (PROS) length (β = -0.278, P = 0.005) and lower retinal vessel density (β = -0.328, P = 0.002). PROS length was positively associated with retinal pigment epithelium (RPE) volume (β = 0.318, P < 0.001). RPE volume was positively associated with serum high-density lipoprotein cholesterol (HDL) levels and negatively associated with oxidized low-density lipoprotein cholesterol (LDL), uric acid and hemoglobin A1c (HbA1c) levels (β = 0.289, -0.216 -0.210, and -0.215, respectively; all P ≤ 0.05). Lower retinal and/or choroidal vascular values were associated with higher HbA1c and high-sensitivity C-reactive protein (hsCRP) levels (β = -0.256 to -0.384; all P ≤ 0.05).</p><p><strong>Conclusion: </strong>This study links subtle macular neural and vascular changes with systemic biomarkers in diabetic patients without visible macular lesions. Impaired central vision was associated with shorter PROS, lower RPE volume, and reduced vascular parameters. These findings improve understanding of early DRD and suggest that monitoring HbA1c, HDL, oxidized LDL, uric acid, and hsCRP may help estimate the risk of visual impairment.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1972307"},"PeriodicalIF":5.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13692711/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149265167","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}

{"title":"ENHO and EDN1 variants link adropin-endothelin-1 imbalance with early vascular aging in adults with and without type 2 diabetes.","authors":"Rooban Sivakumar, K A Arul Senghor, V M Vinodhini, Janardhanan Kumar","doi":"10.3389/fendo.2026.1961984","DOIUrl":"10.3389/fendo.2026.1961984","url":null,"abstract":"<p><strong>Background: </strong>Early vascular aging (EVA) is common in type 2 diabetes, yet its inherited determinants remain undefined. This study examined the associations of ENHO and EDN1 genetic variation with circulating adropin, endothelin-1, their relative imbalance, and early vascular aging in adults with and without T2DM.</p><p><strong>Methods: </strong>This study included 300 adults aged 25-55 years, comprising 150 participants with T2DM and 150 age- and sex-matched controls. Participants were further classified as having Early vascular aging (EVA) (n=116) or Normal vascular aging (NVA) (n=184) using age-referenced estimated pulse wave velocity. ENHO rs2281997 and rs72735260, and <i>EDN1</i> rs5370 and rs2070699 were genotyped by HRM analysis with Sanger confirmation. Gene-specific and total genetic risk scores (GRS) were tested against adropin, endothelin-1, the adropin-endothelin-1 imbalance index (AEI), EVA, and continuous ePWV.</p><p><strong>Results: </strong>In the overall cohort, all four variants were associated with EVA in the risk direction. rs5370 and rs72735260 remained significant after FDR correction. Each additional risk allele in the Total GRS increased the adjusted odds of EVA by 69% (OR 1.691, 95% CI 1.381-2.094), with a graded increase across genetic burden categories. Higher ENHO-GRS was associated with lower adropin, higher EDN1-GRS with higher endothelin-1, and higher Total GRS with greater AEI, which statistically mediated 51.8% of the GRS-EVA association. Within the study cohort, AEI discriminated EVA better than GRS (AUC 0.776 vs 0.661).</p><p><strong>Conclusions: </strong>Combined <i>ENHO</i>-<i>EDN1</i> genetic burden is associated with an adverse adropin-endothelin-1 balance and early vascular aging. Independent replication is required before clinical application.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1961984"},"PeriodicalIF":5.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13680144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149231043","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":"High genetic predisposition and vertebral fracture burden in pregnancy and lactation-associated osteoporosis: clinical insights from a Taiwanese cohort.","authors":"Wei-Yih Chiu, Yu-An Chen, Shyang-Rong Shih, Rong-Sen Yang, Ming-Hsiao Hu, Wen-Ping Yang, Pei-Lung Chen, Keh-Sung Tsai, Wei-Shiung Yang","doi":"10.3389/fendo.2026.1930247","DOIUrl":"https://doi.org/10.3389/fendo.2026.1930247","url":null,"abstract":"<p><strong>Background: </strong>Pregnancy and lactation-associated osteoporosis (PLO) is a rare disorder causing rapid bone loss and severe fragility fractures. While familial clusterings suggest genetic susceptibility, the specific clinical features, genetic landscape, and skeletal recovery trajectory of PLO remain poorly characterized in non-Caucasian populations. This study aimed to evaluate a Taiwanese PLO cohort to optimize diagnostic awareness.</p><p><strong>Methods: </strong>Eleven postpartum women with PLO were evaluated using bone densitometry and spinal imaging. Whole-exome sequencing was performed utilizing a targeted 398-gene skeletal disease virtual panel. Patients were followed longitudinally for a median of 25 months during lactation cessation and/or targeted bone therapy.</p><p><strong>Results: </strong>Seven women developed symptoms after their first pregnancy and four after their second. Vertebral fractures occurred in 91% (10/11) of patients, 80% (8/10) of whom had multi-level involvement predominantly localized to the thoracolumbar spine (T3-L5, peaking at T11-L2). Baseline lumbar bone mineral density (BMD) was significantly lower than hip sites (<i>P</i> = 0.018). Genetic variants were identified in 10 of 11 patients (91%), with six individuals harboring pathogenic variants in <i>WNT1</i>, <i>LRP5</i>, <i>COL10A1</i>, <i>LTBP3</i>, and <i>CALCR</i>. Patients with pathogenic variants exhibited significantly lower lumbar spine BMD than those without (Z-scores: -3.7 vs. -3.0; <i>P</i> = 0.043). Post-treatment, the cohort's median Z-score improved from -3.5 to -2.3 (<i>P</i> = 0.005), though none achieved a score above -1.0.</p><p><strong>Conclusions: </strong>Our findings suggest a significant genetic burden associated with PLO, potentially revealed by pregnancy and lactation stressors. The predominance of vertebral bone loss highlights acute postpartum back pain as a notable clinical sign warranting further investigation. Optimizing long-term maternal outcomes may require rapid diagnostic evaluation, prompt lactation cessation, and the future integration of genotype-informed management strategies.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1930247"},"PeriodicalIF":5.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13680257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237493","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":"Fertility preservation counselling in women with cancer: knowledge, preferences, and unmet needs from a cross-sectional survey.","authors":"Giacomo Corrado, Drieda Zace, Inge Peters, Paola Villa, Luigi Petrella, Alessia Barreca, Lucrezia Massaro, Letizia Lafuenti, Erica Silvestris, Stefano Canosa, Cristina Fabiani, Daniela Rosaria Pia Chieffo, Anna Fagotti, Maria Luisa Di Pietro","doi":"10.3389/fendo.2026.1926475","DOIUrl":"10.3389/fendo.2026.1926475","url":null,"abstract":"<p><strong>Background: </strong>Fertility preservation (FP) is a critical survivorship issue for young women with cancer, yet gaps persist between guidelines and clinical practice. This study assesses knowledge, attitudes, and unmet needs among women referred for specialist counseling.</p><p><strong>Methods: </strong>An observational cross-sectional survey was conducted (November 2022 - June 2026) among women referred to a single tertiary oncofertility center in Rome. A Delphi-informed online questionnaire was completed before the clinical visit. Descriptive statistics and exploratory multivariable logistic regression examined post-diagnosis intention.</p><p><strong>Results: </strong>Among 284 women invited to participate, 260 completed the survey (response rate, 91.5%); 240 patients with a confirmed cancer diagnosis were included in the final analysis (median age, 32 years). Overall, 69.6% were interested in FP, and 94.2% recognized that gonadotoxic treatments could impair fertility. While 89.6% had heard of FP, only half received this information from healthcare professionals, and 24.2% knew of no specific options. Over half reported concerns regarding treatment delay, safety, effectiveness, and cost. Before diagnosis, 73.7% planned to have children; post-diagnosis, positive intention remained common, while those previously without intentions shifted toward uncertainty. In the 188-case model, pre-diagnosis intention showed the strongest association (OR 11.64, 95% CI 4.45-30.48). Given limited model performance (pseudo-R²=0.19), estimates warrant caution.</p><p><strong>Conclusions: </strong>In this single-center referred cohort, informational gaps and uncertainty remained despite high awareness. Findings confirm and contextualize prior evidence in an Italian tertiary setting and may inform similar referral pathways, but require validation in broader populations.</p>","PeriodicalId":12447,"journal":{"name":"Frontiers in Endocrinology","volume":"17 ","pages":"1926475"},"PeriodicalIF":5.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13684863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237481","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}