Calcified Tissue International最新文献

{"title":"Management of a Patient with Severe Osteogenesis Imperfecta Undergoing Laparoscopic Cholecystectomy.","authors":"Sarah Scott, Helen Jordan, Laura Gill, Andreas Luhmann, Jamie Abbott, Stuart H Ralston","doi":"10.1007/s00223-025-01375-9","DOIUrl":"10.1007/s00223-025-01375-9","url":null,"abstract":"<p><p>Individuals with severe osteogenesis imperfecta who require surgery often present a difficult management problem due to limb deformity and shortening, kyphoscoliosis, and deformity of the rib cage. All of these features may be associated with respiratory problems and impaired cardiovascular reserve. Surgical procedures and anaesthetic management represent a substantial challenge in these individuals. Here, we describe the clinical outcome of laparoscopic surgery to remove multiple gallstones in an individual with severe osteogenesis imperfecta. Meticulous pre-operative planning, combined with careful anaesthetic management resulted in a favourable outcome with a beneficial effect on quality of life. We provide a detailed account of the challenges faced and how these were surmounted in the hope that this may be of benefit to other clinicians faced with similar problems. Our experience demonstrates that laparoscopic surgery can be successfully performed in people with severe osteogenesis imperfecta with a favourable outcome.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"72"},"PeriodicalIF":3.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062041/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973032","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}

{"title":"Associations of Markers of Inflammatory Status and Adiposity with Bone Phenotype at Age 60-64 Years: Findings from the MRC National Survey of Health and Development.","authors":"Ruth Durdin, Camille Pearse, Diana Kuh, Rachel Cooper, Elaine M Dennison, Cyrus Cooper, Kate A Ward","doi":"10.1007/s00223-025-01380-y","DOIUrl":"https://doi.org/10.1007/s00223-025-01380-y","url":null,"abstract":"<p><p>This study investigated associations between markers of inflammatory status and adiposity (interleukin-6 [IL-6], adiponectin and leptin) and measures of bone phenotype and fractures. The Medical Research Council (MRC) National Survey of Health and Development (NSHD) is a British birth cohort study. Participants (born during the same week in 1946) with complete data on DXA and pQCT parameters, markers of inflammatory status and adiposity, and potential confounders (498 men and 474 women) were included in cross-sectional analyses. At age 60-64 years, bone phenotype was assessed by DXA and pQCT. Fractures were self-reported at ages 60-64 and 68-70 years. Multiple linear regression was used to determine associations of IL-6, adiponectin and leptin with bone phenotype (adjusted for fat and lean mass and lifestyle confounders). Standard deviation (SD) differences in outcomes per SD increases in exposures were estimated. Higher IL-6 levels were associated with lower total volumetric bone mineral density (vBMD) (- 0.10[- 0.19, 0.00]) in men, and higher areal BMD (aBMD) at the spine (0.12[0.03, 0.22]) and whole body (0.11[0.01, 0.20]) in women. Higher levels of adiponectin were associated with lower aBMD and trabecular vBMD. In women, higher leptin levels were associated with higher cortical vBMD (0.11[0.02, 0.20]). Higher adiponectin was associated with moderately increased odds of having a fragility fracture during adulthood in women (OR 1.16 [95% CI 0.94, 1.43, p = 0.18]). Our results highlight non-mechanical associations between markers of inflammatory status and adiposity with BMD and, in women, fractures. Ensuring inflammaging is minimised may be important in healthy bone ageing.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"71"},"PeriodicalIF":3.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055629/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967851","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}

{"title":"Gene Variants and Bisphosphonates Treatment in Pregnancy and Lactation-Associated Osteoporosis (PLO): A Retrospective Study of 22 Chinese Patients.","authors":"Ziyao Fu, Xiaolin Ni, Sirui Han, Mei Li, Ou Wang, Xiaoping Xing, Yan Jiang, Weibo Xia","doi":"10.1007/s00223-025-01381-x","DOIUrl":"https://doi.org/10.1007/s00223-025-01381-x","url":null,"abstract":"<p><p>Pregnancy and lactation-associated osteoporosis (PLO) is a rare bone disorder with insufficient understanding on its pathogenesis and treatments. We retrospectively investigated 22 Chinese PLO patients diagnosed in our hospital. Whole exome sequencing was performed in 14 patients, and responses to bisphosphonates treatment were evaluated. The mean age of the patients was 30.8 ± 4.4 years. The mean number of vertebral fractures per patient was 4.0 ± 2.6. The bone mineral density (BMD) Z-scores were - 2.9 ± 0.9 at the lumbar spine (LS), - 1.7 ± 0.7 at the femoral neck, and - 1.8 ± 0.7 at the total hip. Trabecular bone score Z-score was - 2.2 ± 0.8. Genetic analysis identified relevant variants (RVs) in 11 of 14 patients, predominantly in LRP5, WNT1, and COL1A1/A2. Patients with RVs had significantly greater height loss (3.6 ± 2.1 cm vs. 0 cm, p = 0.028). All patients received bisphosphonate therapy, during which increases in BMD primarily at the LS were observed: 13.5 ± 8.8%, 17.8 ± 14.7%, 22.0 ± 17.0%, 27.0 ± 14.1% and 35.1 ± 18.5% at the 6-, 12-, 24-, 36-, and 48-month follow-ups. Patients with RVs demonstrated LS BMD percentage changes of 40.1 ± 22.1% (vs. no RVs group 26.2 ± 14.8%, p = 0.57) after 48-month follow-ups. In conclusion, our study highlights the significant clinical burden of PLO. Genetic RVs are prevalent in Chinese PLO patients. After bisphosphonate treatment, there is a significant increase in BMD, especially in LS. Patients with RVs have the potential of more robust therapeutic response.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"70"},"PeriodicalIF":3.3,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954116","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":"Associations of Serum Vitamin D with Sarcopenia in Patients with Chronic Liver Disease: A Population-Based Cross-Sectional Study.","authors":"Xinxing Tantai, Zhang Wen, Shuyue Tuo, Qiuju Ran, Chan Li, Yong Li, Jia Yuan, Jinhai Wang, Lu Li, Shejiao Dai","doi":"10.1007/s00223-025-01376-8","DOIUrl":"https://doi.org/10.1007/s00223-025-01376-8","url":null,"abstract":"<p><p>The association between vitamin D and sarcopenia in patients with chronic liver disease (CLD) has yet to be conclusively established, particularly in Western populations. We investigated the association between serum 25(OH)D levels and sarcopenia in adult CLD patients in the USA. We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey III. Weighted logistic regression was used to determine the association between sarcopenia and serum 25(OH)D in participants with CLD. CLD was defined as chronic hepatitis B or C, non-alcoholic fatty liver disease, alcohol-related liver disease, and other liver diseases. A serum 25(OH)D level of less than 75 nmol/L was defined as vitamin D insufficiency. This study included 1402 participants with CLD. The serum 25(OH)D concentration was significantly lower in the sarcopenia group (45.3 nmol/l) compared to the non-sarcopenia group (50.6 nmol/l). The prevalence of vitamin D insufficiency was as high as 91.3% in participants with CLD, and the proportion of vitamin D insufficiency was higher in those with sarcopenia. In the full multivariate model, each 10-nmol/L increase in 25(OH)D concentration was significantly associated with a decreased risk of sarcopenia (OR 0.89; 95%CI 0.79-0.99). Conversely, participants with insufficient vitamin D levels had a significantly increased risk of sarcopenia (OR, 2.07; 95% CI 1.08-4.00). Subgroup analyses suggested a sex difference in the association between vitamin D levels and sarcopenia, with a significant association only observed in females. Restricted cubic spline curves indicated a linear inverse association between serum 25(OH)D concentration and risk of sarcopenia in all participants and in females. Low serum 25(OH)D levels were significantly associated with an increased risk of sarcopenia in individuals with CLD, with the observed gender differences in this association warranting further validation in future studies.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"69"},"PeriodicalIF":3.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984377","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":"Developing a Standardised Dataset for Natural History Studies in Fibrous Dysplasia/McCune-Albright Syndrome.","authors":"Ana Luisa Priego Zurita, Oana O Bulaicon, Jillian Bryce, Nerea Arrieta, Magdalena Caballero Campos, Mariya Cherenko, Gaby Doxiadis, Corinna Grasemann, M Kassim Javaid, Helen McDevitt, Stijn W van der Meeren, Diana Ovejero Crespo, Luisa de Sanctis, Lothar Seefried, Annemarie A Verrijn Stuart, Daniele Tessaris, Pieter Bas de Witte, Roland Chapurlat, S Faisal Ahmed, Natasha M Appelman-Dijkstra","doi":"10.1007/s00223-025-01379-5","DOIUrl":"https://doi.org/10.1007/s00223-025-01379-5","url":null,"abstract":"<p><p>Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare and complex condition caused by somatic variants in the GNAS gene that lead to a wide clinical spectrum. The diagnostic process and therapeutic pathway vary per centre and therefore international harmonisation of data collection should be pursued. To understand the diagnostic pathways and clinical outcomes of patients with FD/MAS reported on an electronic-reporting tool (e-REC) across European centres to guide the develop a condition-specific module within the European Registries for Rare Endocrine and Bone conditions. Centres that reported new cases on e-REC between October 2019 and May 2021 were approached to complete a survey in May 2021. Fifty-eight cases were included. Median age at presentation was 20 years (range, 0, 72). Of the 58 included cases, the presentation type was isolated craniofacial FD in 19 (33%), monostotic FD in 15 (26%), polyostotic FD in 10 (17%), and MAS in 13 (13%). Standardised questionnaires to assess pain and quality of life were used routinely in 21/58 patients (36%). The majority of patients had more than one healthcare provider, with great diversity in the specialty of the coordinating physician. A standardised dataset module for FD/MAS was developed through collaboration with the FD/MAS study group, incorporating expert consensus and clinical insights. Key variables were identified to capture essential diagnostic, clinical, and patient-reported outcomes. The diagnostic path for patients with FD/MAS across European expert centres is variable. The outcomes of this study allowed the building of the first international FD/MAS-specific data collection.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"68"},"PeriodicalIF":3.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990009","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}

{"title":"Accuracy of Low-Dose Chest CT-Based Artificial Intelligence Models in Osteoporosis Detection: A Systematic Review and Meta-analysis.","authors":"Huang Ya'nan, Zhou Jianfeng, Tang Wei, Yang Jianfeng, Zhao Zhenhua","doi":"10.1007/s00223-025-01377-7","DOIUrl":"10.1007/s00223-025-01377-7","url":null,"abstract":"<p><p>The purpose of this study is to systematically review and evaluate the accuracy of low-dose chest CT-based artificial intelligence in osteoporosis screening. A systematic literature search for relevant studies up to 13th December 2024 was performed in the PubMed, Scopus, Web of Science, and Cochrane Library databases. This meta-analysis was conducted in accordance with the PRISMA-DTA statement. Modified QUADAS-2 was used to assess the methodological quality of the studies. Quantification bias metrics were extracted to evaluate the performance of the AI models for vertebrae segmentation and labeling based on low-dose chest CT images. Pooled sensitivity, specificity, and area under the curve (AUC) were calculated. To assess publication bias, Egger test and funnel plot were conducted. Meta-regression and subgroup analysis were performed to explore potential heterogeneity. Eight studies suitable for the analysis were included. The pooled Dice similarity coefficient (DSC) for automatic vertebrae segmentation was 0.92 (95% CI 0.88-0.97). For the diagnosis of abnormal (osteoporosis + osteopenia) or osteoporosis participants, respectively, pooled sensitivities were 0.90 (95% CI 0.88-0.91) and 0.86(95% CI 0.82-0.89); pooled specificities were 0.90 (95% CI 0.88-0.91) and 0.93 (95% CI 0.92-0.94); and summary receiver operating characteristic (SROC) curves were 0.9653 and 0.9676. Meta-regression and subgroup analyses identified potential sources of heterogeneity, including result source (external dataset vs. internal dataset), ROI annotations (one radiologist vs. two radiologists), model developed with or without radiomics, and VBs segmentation output (included lumbar spine vs. only thoracic spine) (P < 0.05). The low-dose chest CT-based AI model shown promise information for identifying patients with osteoporosis or osteopenia who need further evaluation. Further prospective multi-center, multi-dataset studies are still required to assess the complementary role of the AI model in osteoporosis and osteopenia diagnosis through low-dose chest CT images.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"67"},"PeriodicalIF":3.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960160","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 Child with Cutaneous-Skeletal Hypophosphatemia Syndrome Caused by a Mosaic HRAS Mutation: Outcome of Treatment with Anti-FGF23 Antibody.","authors":"Jing Wu, Qiaoyu Cao, Wei Lu, Chengjun Sun, Qiuyue Li, Rong Ye, Ruoqian Cheng, Feihong Luo, Ming Li","doi":"10.1007/s00223-025-01373-x","DOIUrl":"https://doi.org/10.1007/s00223-025-01373-x","url":null,"abstract":"<p><p>Cutaneous-skeletal hypophosphatemia syndrome (CSHS) is a rare mosaic disorder that causes bone abnormalities due to hypophosphatemic rickets and skeletal dysplasia and is a significant health comorbidity. Conventional therapy involving multiple daily oral doses of phosphate and calcitriol for CSHS patients has limited effectiveness. We report the clinical features and therapeutic outcomes of the first Chinese child diagnosed with CSHS, who presented with bone fractures, a history of seizures, and recurrent gastrointestinal manifestations, including diarrhoea and bowel obstruction. The effectiveness of conventional therapy and an anti-FGF23 antibody (burosumab) was evaluated. Ultra-deep sequencing was performed on the patient's blood DNA, skin tissue, oral mucosa, and hair follicles to identify causative mutations. The child had a somatic mutation in the HRAS (p.G13R) gene, which was identified at low variant allele frequencies. We analysed the sequencing results from reported cases and determined that the sequencing of lesional tissues, such as skin and bone, is preferable to that of oral mucosa or potentially affected hair follicles for establishing a definitive diagnosis of CSHS. Compared with conventional phosphate therapy, burosumab resulted in a steady increase in blood phosphorus levels and significant improvements in patient mobility, pain outcomes and skeletal radiography. It is suggested that younger children may receive a higher initial dosage of burosumab for better outcomes. However, long-term follow-up is still necessary to confirm its efficacy and safety.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"65"},"PeriodicalIF":3.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966439","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 Diagnosis and Therapy of XLH.","authors":"Ineke Böckmann, Dieter Haffner","doi":"10.1007/s00223-025-01374-w","DOIUrl":"https://doi.org/10.1007/s00223-025-01374-w","url":null,"abstract":"<p><p>X-linked hypophosphatemia is a rare genetic disease caused by pathogenic variants in the PHEX (phosphate-regulating endopeptidase homolog X-linked) gene with X-linked dominant inheritance that causes metabolic bone disease and other severe complications. PHEX dysfunction results in increased production and secretion of the phosphaturic hormone fibroblast growth factor 23 (FGF23) from bone. The consequences of FGF23 excess are renal phosphate wasting and decreased calcitriol synthesis, leading to hypophosphatemia and subsequently rickets and osteomalacia. Children with XLH usually become symptomatic in the second year of life presenting with progressive disproportionate short stature, bone pain, frontal bossing, enlarged joints, bowed legs, and a waddling gait. Various other symptoms may develop later, including dental abscesses, peritonitis, hearing loss, pseudofractures, spinal stenosis, osteoarthritis, and enthesopathies, often leading to a diminished quality of life and ultimately disability. Here, we provide an overview of the current knowledge of the pathophysiology and treatment insights of this rare and challenging disease, including the targeting of FGF23 as a therapeutic approach that has significantly improved patient outcomes.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"66"},"PeriodicalIF":3.3,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12037658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954700","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}

{"title":"Investigation of Osteoporosis in Persons Living with Human Immunodeficiency Virus: The HOST Study.","authors":"Simone Bruhn Rosendahl, Jakob Starup-Linde, Merete Storgaard, Bente Langdahl","doi":"10.1007/s00223-025-01368-8","DOIUrl":"https://doi.org/10.1007/s00223-025-01368-8","url":null,"abstract":"<p><p>Bone health is an emerging concern in the aging human immunodeficiency virus (HIV)-infected population. We aimed to investigate bone mineral density (BMD) and bone microarchitecture in persons living with HIV (PLHIV). The study was a cross-sectional study. BMD and bone microarchitecture were investigated by Dual-Energy X-ray Absorptiometry (DXA) at the hip and lumbar spine and High-Resolution peripheral Quantitative Computed Tomography (HRpQCT) at the radius and tibia. Information about risk factors for fracture was obtained from a questionnaire. 183 PLHIV were included, 160 (131 males, 29 females) completed the visit. Age range was 30-78 years and the mean time since first HIV-positive serology was 16.5 years. 47% had low bone density and 6% had osteoporosis. The mean T-score by DXA was - 1.2 (standard deviation (SD) ± 1.0), - 0.7 (SD ± 0.9), and - 0.7 (SD ± 1.3) at the femoral neck, total hip and lumbar spine, respectively. We observed no significant difference in BMD by DXA between participants below or above age 50. BMI was significantly lower in PLHIV with lower BMD (p = 0.001, ANOVA). HRpQCT measurements showed significant differences in cortical area, volumetric BMD, and most microarchitecture parameters between PLHIV with BMD in the normal, low, and osteoporotic ranges measured at the tibia and radius. Our results indicate that bone microarchitecture and BMI vary considerably between PLHIV with normal, low, and osteoporotic BMD. These differences may partly explain the increased fracture risk seen in PLHIV.Trial numbers: Ethics Committee of the Central Denmark Region (case no. 1-10-72-238-17), Danish Data Protection Agency (case no. 1-16-02-708-17).</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"64"},"PeriodicalIF":3.3,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12031905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062452","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}

{"title":"Keto Acids Attenuate Skeletal Muscle Atrophy in Chronic Kidney Disease via Inhibiting Pyroptosis and Upregulating Irisin Precursor FNDC5 Expression.","authors":"Peixin Wang, Qi Pang, Aihua Zhang","doi":"10.1007/s00223-025-01372-y","DOIUrl":"https://doi.org/10.1007/s00223-025-01372-y","url":null,"abstract":"<p><p>It is widely accepted that keto acids supplementation can protect skeletal muscle from atrophy. Pyroptosis has been considered to be one of the new mechanisms of muscle atrophy. This study aimed to explore the effects and mechanisms of keto acids supplementation on chronic kidney disease (CKD)-induced skeletal muscle atrophy. In vitro, C2C12 myoblast cells were treated with indoxyl sulfate (IS, 1 mM) and leucine (Leu, 0 ng/mL, 50 ng/mL or 100 ng/mL). In animal experiment, animals were divided into four groups: normal control (NC) group (wildtype mice), CKD group (wildtype mice with CKD modeling), keto acids (KAs) group (CKD wildtype mice treated with KA), and FNDC5-/- group (Fndc5 (irisin precursor) gene knockout mice with CKD modeling and KA treatment). Results showed that leucine improved IS-induced myotube atrophy, decreased percentage of Propidium Iodide (PI)-positive cells, upregulated FNDC5 expression levels, and downregulated the pyroptosis-related protein levels, such as NLRP3, cleaved CASP1, and GSDMD-N. KA supplementation improved renal function and skeletal muscle atrophy. Furthermore, KA supplementation suppressed the expression of pyroptosis-related proteins and increased the expression of FNDC5. However, Fndc5 gene knockout partially reversed the protective effects of keto acids in CKD. In conclusion, our results showed for the first time that KA supplementation improves CKD-induced skeletal muscle atrophy by inhibiting pyroptosis and increasing expression of irisin/FNDC5. Our findings provide a novel insight into the treatment of the CKD-induced skeletal muscle atrophy.</p>","PeriodicalId":9601,"journal":{"name":"Calcified Tissue International","volume":"116 1","pages":"63"},"PeriodicalIF":3.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143980383","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}