Endocrine Connections最新文献

{"title":"Structured Physiotherapy Improves Functional Outcomes in Acromegalic Arthropathy After Biochemical Remission: A Prospective Controlled Study.","authors":"Merve Korkmaz Yilmaz, Evrim Coskun, Busra Karanfil, Mutlu Niyazoglu, Esra Hatipoglu","doi":"10.1530/EC-26-0506","DOIUrl":"https://doi.org/10.1530/EC-26-0506","url":null,"abstract":"<p><strong>Background: </strong>Musculoskeletal symptoms frequently persist in acromegaly despite biochemical remission, yet the impact of structured physiotherapy on pain, stiffness, and function remains poorly defined.</p><p><strong>Objective: </strong>To evaluate the effects of a standardized knee-focused physiotherapy program in controlled acromegaly and to identify clinical predictors of treatment responsiveness.</p><p><strong>Methods: </strong>Thirteen patients with acromegaly in remission and 13 age-, gender-, and BMI-matched individuals with primary knee osteoarthritis completed a 15-session physiotherapy program. Outcomes were assessed pre- and post-intervention using the Brief Pain Inventory (BPI) and WOMAC. Minimal clinically significant difference (MCID) thresholds (≥2 for BPI, ≥10 for WOMAC) determined meaningful improvement. Correlation analyses examined associations between clinical variables and Δ scores.</p><p><strong>Results: </strong>Acromegaly patients showed significant improvements in all BPI and WOMAC domains (p<0.001). MCID was achieved by 85% for BPI and 100% for WOMAC Total. Pain and function improved most, whereas stiffness showed limited responsiveness. Compared with osteoarthritis controls, acromegaly patients demonstrated smaller Δ changes; baseline-adjusted analyses (ANCOVA) indicated that this attenuated response was largely explained by greater baseline severity in the control group, whereas the persistently greater stiffness in acromegaly remained significant even after adjustment. BMI correlated positively with improvements in BPI Total (r = 0.63) and BPI Pain Severity (r = 0.69), while adenoma size correlated negatively with both measures (r = -0.57 and -0.60). BMI showed a negative association with WOMAC Total improvement (r = -0.59). Stiffness changes were strongly negatively correlated with pretreatment IGF-1 (r = -0.77).</p><p><strong>Conclusion: </strong>Structured physiotherapy yields clinically meaningful improvements in pain and function in acromegaly, while stiffness appears less reversible and more structurally driven. Early musculoskeletal assessment and physiotherapy integration may enhance long-term management.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Single-Centre Audit of Bone-Modifying Agents in Neuroendocrine Neoplasm Bone Metastases\".","authors":"Wessam Osman, Preetha Aravind, Hemanth Prabhudev, Jeannie Todd, Ramona Nistor, Antonio D'Alessio, Rohini Sharma, Tami Grunewald, Florian Wernig","doi":"10.1530/EC-26-0252","DOIUrl":"https://doi.org/10.1530/EC-26-0252","url":null,"abstract":"<p><p>Bone metastases in neuroendocrine neoplasms are uncommon but cause significant morbidity. A recent Italian survey of 320 patients with neuroendocrine neoplasms and bone metastases reported skeletal-related events in 23% and bone-targeted agent use in 31%, highlighting limited evidence for bone-modifying agents. We identified adults with confirmed or clinically suspected neuroendocrine bone involvement who received a bone-modifying agent at a UK tertiary centre (January 2019-September 2024), using institutional prescribing records. Demographic, tumour, treatment, and toxicity data were extracted from records. Twenty-two patients received treatment (denosumab 17 [77%], zoledronic acid 5 [23%]). Most (91%) had grade 1-2 tumours; 64% had gastro-entero-pancreatic primaries. Bone metastases were synchronous in 46% and widespread (more than three lesions) in 73%. At diagnosis, 22% were symptomatic; during follow-up, 78% developed pain, high blood calcium, or a skeletal-related event. Skeletal-related events, a composite of pathological fracture, spinal cord compression, radiotherapy to bone, or orthopaedic surgery, occurred in 41% (radiotherapy alone in 36%); pain-relieving medication was used universally. Treatment was mainly given every 12 weeks (median six doses). Low blood calcium occurred in 9% and osteonecrosis of the jaw in 5%; dental assessment before therapy was recorded in only 9%. These figures are broadly consistent with the Italian survey cited above. Treatment use was heterogeneous, reflecting a lack of disease-specific guidelines, and toxicity was comparable to other solid tumours and generally manageable. Our findings highlight the need for prospective studies and structured registries to clarify treatment use, dosing, and impact on quality of life and prognosis.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Health-Related Quality of Life in Benign Thyroid Diseases Assessed by ThyPRO: A Systematic Review and Meta-Analysis.","authors":"Nadia Sawicka-Gutaj, Aleksandra Derwich-Rudowicz, Barbara Bromińska, Joanna Maciejewska, Kacper Nijakowski, Paulina Kozłowska, Oliwier Adamczak, Zachariasz Rytelewski, Angelos Kyriacou, Marek Ruchała","doi":"10.1530/EC-26-0097","DOIUrl":"https://doi.org/10.1530/EC-26-0097","url":null,"abstract":"<p><strong>Purpose: </strong>Benign thyroid diseases are common conditions that often require long-term treatment. In some patients, symptoms persist despite normalization of biochemical parameters, significantly affecting quality of life (QoL). This study evaluated treatment-associated changes in QoL using the Thyroid Patient Reported Outcome (ThyPRO) questionnaire and summarized differences in QoL profiles reported across thyroid conditions.</p><p><strong>Methods: </strong>A systematic review and meta-analysis were performed according to PRISMA guidelines. PubMed, Scopus, and Embase were searched up to April 2024. Data were extracted and synthesized using standardized mean differences.</p><p><strong>Results: </strong>Twenty-five studies were included. Significant pre-post-treatment improvements in overall QoL and selected symptom domains were observed. In Graves' disease, improvements were observed in hyperthyroid symptoms, anxiety, impaired daily life, and overall QoL. In non-toxic goiter, improvements were observed in goiter symptoms, cosmetic complaints, anxiety, tiredness, and overall QoL. In toxic nodular goiter, significant improvements were observed in hyperthyroid and goiter symptoms and overall QoL, whereas several other domains did not change significantly. In hypothyroidism, significant improvements were observed in selected domains, including tiredness, impaired daily life, mood-related symptoms, and overall QoL. Analyses comparing ThyPRO scores between patient groups showed differences in selected domains; these comparisons were interpreted descriptively.</p><p><strong>Conclusions: </strong>Treatment was associated with improvements in QoL across the analyzed benign thyroid conditions, varying by disease group. Given the heterogeneity of the included studies and the absence of head-to-head comparisons of treatment efficacy across conditions, these findings should be interpreted descriptively. Disease-specific QoL assessment may help clinicians identify persistent symptom domains requiring attention during follow-up.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuous Glucose Monitoring Reveals Glycemic Profile in Adrenal Insufficiency Patients on Glucocorticoid Replacement.","authors":"Cuili Ning, Rui Zhang, Wei Liu, Xianghai Zhou, Yunyang Sun, Xueyao Han, Linong Ji, Qian Ren","doi":"10.1530/EC-26-0304","DOIUrl":"https://doi.org/10.1530/EC-26-0304","url":null,"abstract":"<p><strong>Objective: </strong>Hypoglycemia is common in the patients with adrenal insufficiency (AI), who require lifelong glucocorticoid replacement therapy. However, whether this therapy restores physiological glycemic fluctuations in the patients with AI remains unclear. This study aimed to characterize glucose fluctuation pattern in the patients with AI using continuous glucose monitoring (CGM).</p><p><strong>Methods: </strong>Twenty-seven patients with AI on stable doses of glucocorticoid were consecutively enrolled. Fifty-four age-, sex-, and BMI-matched normal controls (NC) were selected from a healthy volunteer database at a 2:1 ratio. CGM was conducted with a blinded method for 14 days. Glucocorticoid regimen and adverse events during CGM were documented.</p><p><strong>Results: </strong>The AI group had a mean age of 59.53±8.51 years (15 males). Compared with NC, the patients with AI exhibited increased time below range (TBR, glucose <3.9 and <3.0 mmol/L) and decreased time in range (TIR, glucose within 3.9-7.8 mmol/L). Time above range (TAR, glucose ≥7.8 mmol/L) were elevated during the lunch and dinner periods, and glucose fluctuation parameters were also increased. CGM-detected hypoglycemia was observed in all patients (27/27, 100%) versus 46/54 (85.2%) controls (p = 0.047). The patients receiving once-daily glucocorticoid had higher lunchtime TAR than those on twice-daily dosing. Hydrocortisone-treated patients showed higher breakfast and lunchtime TAR compared with prednisone users. Patients with immune checkpoint inhibitors (ICIs) induced AI had higher glucose levels and fluctuation parameters during breakfast and dinner periods than those with other etiologies.</p><p><strong>Conclusions: </strong>Patients with AI receiving glucocorticoid replacement experience more frequent CGM-recorded asymptomatic hypoglycemia and greater glucose variability. CGM may provide valuable insights for optimizing glucocorticoid administration strategies in AI.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A nomogram integrating first-trimester metabolic and angiogenic markers for predicting adverse pregnancy outcomes in gestational diabetes mellitus: development and internal validation.","authors":"Jingli Fu, Xiaoyan Zhong, Dan Li, Siying Zhuang, Weiwei Yu","doi":"10.1530/EC-26-0478","DOIUrl":"https://doi.org/10.1530/EC-26-0478","url":null,"abstract":"<p><strong>Background: </strong>Gestational diabetes mellitus (GDM) is associated with a significantly increased risk of adverse pregnancy outcomes. This study aimed to develop and internally validate a nomogram integrating integrating first-trimester metabolic and angiogenic markers to predict composite adverse pregnancy outcomes in GDM.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of 1,000 GDM patients (training set n=700, validation set n=300). Multivariable logistic regression was used to identify independent predictors and construct a nomogram. Model performance was assessed by discrimination (area under the receiver operating characteristic curve [AUC]), calibration (Hosmer-Lemeshow test, calibration plots), and decision curve analysis (DCA).</p><p><strong>Results: </strong>Six variables were retained as independent predictors: pre-pregnancy BMI, FPG, TG, HOMA-IR, PIGF, and sFlt-1. The full model showed excellent discrimination in internal validation, with an AUC of 0.87 (95% CI 0.84-0.90) in the training set and 0.84 (95% CI 0.80-0.88) in the validation set, significantly outperforming a metabolic-only model without PIGF/sFlt-1 (AUC 0.82, p=0.01). Calibration was good (Hosmer-Lemeshow p=0.36 and 0.42, respectively). DCA demonstrated clinical net benefit across threshold probabilities of 0.15-0.35. Subgroup analyses confirmed stable performance across age, BMI, treatment, and parity.</p><p><strong>Conclusion: </strong>The nomogram incorporating first-trimester metabolic and angiogenic markers accurately predicts adverse pregnancy outcomes in GDM patients in this internal validation cohort.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149166681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post-cycle therapy after androgen abuse: what are we seeking to achieve?","authors":"Bonnie Grant, Channa N Jayasena","doi":"10.1530/EC-26-0709","DOIUrl":"https://doi.org/10.1530/EC-26-0709","url":null,"abstract":"<p><p>Despite limited evidence supporting its efficacy, the use of post-cycle therapy (PCT) is widespread amongst men following cessation of androgen abuse. The proposed rationale for PCT is to accelerate recovery of hypothalamic-pituitary-gonadal (HPG) axis function following androgen-induced suppression. In this commentary, we consider the distinction between pharmacological response and sustained recovery of endogenous HPG axis function, the relationship between biochemical and symptomatic recovery, and the potential role of PCT as a harm-reduction strategy.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The hormonal management of adults with gender incongruence: what the non-specialist Endocrinologist needs to know. A position statement from the Society for Endocrinology.","authors":"Channa N Jayasena, Anastasia Dimakopoulou, Richard A Anderson, Ruth Bond, Victoria Millson-Brown, Simon Stockley, Leighton Seal, Richard Quinton","doi":"10.1530/EC-26-0163","DOIUrl":"https://doi.org/10.1530/EC-26-0163","url":null,"abstract":"<p><p>Individuals discharged from specialist gender identity services continue to require coordinated hormonal, medical, and psychosocial care. Despite this, there are limited standardised pathways for the transition of care from specialist clinics to ongoing primary care settings. This was developed by a multidisciplinary team including endocrinologists, specialist gender clinicians, reproductive medicine specialists and general practice. It draws on existing service specifications and shared-care protocols. The position statement emphasises the need for clear documentation at discharge from the gender identity clinic, including the hormone regimen, monitoring schedule, and risk stratification. It advocates a collaborative approach between specialist gender clinics and primary care providers. It also highlights the importance of patient education and empowerment for lifelong monitoring needs, lifestyle risk mitigation, such as smoking cessation, weight management, cardiovascular health, as well as contraception and fertility considerations. It provides guidance on when to seek specialist referral for hormonal management, and to adopt a multidisciplinary approach once complications or changes arise. This position statement supports minimal effective hormone dosing when appropriate, and the adoption of pragmatic strategies in later life or palliative contexts. A coordinated, patient-centred approach is key to optimizing long-term outcomes and ensuring safe, effective continuation of gender-affirming care.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149135499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term health outcomes and comorbidities in cytochrome P450 oxidoreductase (POR) deficiency: a scoping review of evidence and knowledge gaps.","authors":"Chrysanthi Kouri, Asmitha Thirukkumar, Christa E Flück","doi":"10.1530/EC-26-0354","DOIUrl":"10.1530/EC-26-0354","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>P450 oxidoreductase deficiency (PORD) is a rare congenital disorder of steroidogenesis caused by pathogenic variants in POR, the obligate electron donor to all microsomal cytochrome P450 (CYP) enzymes. While the early clinical presentation of PORD - characterized by adrenal insufficiency, differences of sex development, and Antley-Bixler-like skeletal malformations - is well established, its long-term consequences remain poorly defined. This scoping review synthesizes current evidence on multisystem outcomes in PORD and integrates insights from the broader biology of POR-dependent enzymes to inform potential long-term risks. Across 51 known POR-partner enzymes, numerous polymorphisms have been associated with cardiovascular, metabolic, reproductive, skeletal, neurological, inflammatory, and oncological phenotypes in the general population. Although many of these conditions have not yet been reported in PORD, their mechanistic plausibility highlights important gaps in surveillance. Emerging clinical observations, including hypertension, altered drug metabolism, impaired fertility, and reduced bone health, further underscore the need for systematic long-term follow-up. Experimental models additionally suggest vulnerabilities related to lipid accumulation, bile acid dysregulation, and hepatocellular injury. Despite these concerns, no evidence-based guidelines exist for the lifelong management of PORD, and psychosocial outcomes remain entirely unexplored. Collectively, the available data indicate that PORD is a multisystem disorder with potential age-dependent manifestations extending beyond childhood. Prospective longitudinal studies, mechanistic investigations, and coordinated international registry efforts are essential to define the true long-term phenotype and to develop standardized monitoring and management strategies for affected individuals.</p><p><strong>Lay summary: </strong>P450 oxidoreductase deficiency (PORD) is a rare genetic condition that affects many body systems because the POR enzyme supports dozens of important metabolic pathways. Most research has focused on early symptoms, such as hormone problems, differences in sex development, and bone abnormalities. Much less is known about how PORD affects people later in life. This review brings together current evidence and highlights possible long-term risks, including high blood pressure, liver and metabolic problems, reduced fertility, and bone health issues. Longer-term studies are urgently needed to understand these risks and to guide better care for individuals with PORD.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149024284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A cross-sectional online survey of quality of life in adults with Klinefelter syndrome in the UK.","authors":"Brien Mehmet, Andrew A Dwyer, Channa N Jayasena, Steve Gillard, Sofia Llahana","doi":"10.1530/EC-26-0419","DOIUrl":"10.1530/EC-26-0419","url":null,"abstract":"<p><p>Klinefelter syndrome (KS) is the most common sex chromosome disorder in males and the leading genetic cause of hypogonadism, affecting approximately 1 in 450-600 male births. Despite its prevalence, many individuals remain undiagnosed. Although European cohort studies have demonstrated poorer health-related quality of life (HR-QoL) among individuals with KS, evidence from the United Kingdom remains limited. This cross-sectional online survey explored HR-QoL and perceived self-efficacy in clinical communication among adults with KS in the United Kingdom. Sixty adults with a confirmed diagnosis of KS were recruited through the Klinefelter Syndrome Association (UK). Participants completed validated measures of HR-QoL (WHOQOL-BREF) and Perceived Efficacy in Patient-Physician Interactions (PEPPI-5), alongside clinical and sociodemographic questions. Participants reported a broad range of physical and psychological comorbidities, with 32 (53%) of participants self-reporting depression and/or anxiety. Compared with the UK normative data (n = 141), participants with KS demonstrated significantly lower HR-QoL scores across all WHOQOL-BREF domains. Linear regression analyses showed that greater perceived self-efficacy in clinician-patient communication was associated with better HR-QoL outcomes across all WHOQOL-BREF domains after adjustment for body mass index, comorbidity count, and self-reported depression and/or anxiety, with adjusted coefficients ranging from B = 4.06 to 6.98 WHOQOL points per 5-point increase in PEPPI-5 (P ≤ 0.022 for all domains). These findings highlight the substantial impact of KS on quality of life and emphasise the importance of interventions aimed at improving communication, supportive care, and patient engagement to enhance HR-QoL outcomes in adults with KS.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149037087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring causal associations between the plasma proteome and bone mineral density: a Mendelian randomization study.","authors":"Kui Lv, Jialiu Fang, Shengyou Wang, Xing Xing, Rui Zhu","doi":"10.1530/EC-25-0180","DOIUrl":"10.1530/EC-25-0180","url":null,"abstract":"<p><strong>Introduction: </strong>Osteoporosis is characterized by reduced bone mineral density (BMD) and an increased risk of fractures, but the relationships between plasma proteins and site-specific BMD phenotypes remain unclear. We aimed to investigate the potential causal associations of plasma proteins with BMD using a Mendelian randomization (MR) analysis.</p><p><strong>Methods: </strong>We conducted a two-sample MR analysis as the primary analysis, using cis-protein quantitative trait locus (pQTL) instruments from nine proteomic genome-wide association studies and summary statistics for total-body, forearm, femoral-neck, and lumbar-spine BMD. Prioritized associations were evaluated using colocalization, Steiger directionality testing, protein-altering variant (PAV) annotation, cis-expression quantitative trait locus (cis-eQTL) overlap, and targeted replication. Protein-protein interaction (PPI), pathway enrichment, and druggability analyses were exploratory.</p><p><strong>Results: </strong>Twenty-three study-specific associations met the significance thresholds and involved 12 proteins: F2, TGFBI, PLEKHA1, HTRA1, PKDCC, CFHR4, LRP4, RSPO3, DKK1, TNFRSF11A, SPP1, and IBSP. Strong colocalization supported associations of F2 with total-body BMD, TGFBI with femoral-neck BMD, and PLEKHA1 with total-body and lumbar-spine BMD. Steiger testing supported directionality for 22 of 23 associations, except PKDCC-forearm BMD. Targeted replication provided no statistically significant, directionally concordant support. LRP4 relied on the only direct target-protein PAV, while eight cis-pQTLs for six proteins overlapped with cis-eQTLs. Exploratory analyses implicated skeletal and extracellular matrix processes and targets of prior pharmacological interest.</p><p><strong>Conclusion: </strong>Using cis-pQTL-based MR, we identified circulating proteins associated with BMD phenotypes. Strong colocalization was observed for F2, TGFBI, and PLEKHA1, whereas the remaining associations require additional validation. These findings provide genetic support for established bone-related pathways and highlight candidate proteins.</p>","PeriodicalId":11634,"journal":{"name":"Endocrine Connections","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}