Bone最新文献

{"title":"Biomarkers and therapeutic targets in giant cell tumor of bone: A comprehensive review","authors":"Veronika Knechtova ,&nbsp;Michal Mahdal ,&nbsp;Iva Staniczkova Zambo ,&nbsp;Jan Skoda ,&nbsp;Jakub Neradil","doi":"10.1016/j.bone.2025.117566","DOIUrl":"10.1016/j.bone.2025.117566","url":null,"abstract":"<div><div>Giant cell tumor of bone (GCTB) is an intermediate locally aggressive osteolytic tumor with low metastatic potential and a high recurrence rate. It comprises two main types of cells—neoplastic mononuclear stromal cells and osteoclast-like giant cells—which are responsible for the resorption of bone. In addition to surgery, which is the primary treatment of choice, adjuvant therapy is used to lower the risk of recurrence. However, denosumab, the standard adjuvant treatment currently used, only targets osteoclast-like giant cells and does not affect neoplastic stromal cells. Since some GCTBs are inoperable, or even after surgery, there can be residual tumor cells at the site of the tumor, novel therapies, especially those that target neoplastic stromal cells, are needed. Both cell types in GCTB show altered expression of various specific genes and molecules, and these deregulated molecular profiles could serve as biomarkers and targets for targeted therapy. Herein, we summarize the potential biomarkers for both cell types in GCTB and therapeutic agents targeting these molecules with the hope of finding a therapy with improved outcomes and a lower risk of recurrence.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"199 ","pages":"Article 117566"},"PeriodicalIF":3.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potent suppression of bone remodeling by denosumab does not blunt the anabolic response to romosozumab in mice","authors":"Cecile Bustamante-Gomez ,&nbsp;Qiang Fu ,&nbsp;Joseph J. Goellner ,&nbsp;Jeff D. Thostenson ,&nbsp;Humberto Reyes-Pardo ,&nbsp;Charles A. O'Brien","doi":"10.1016/j.bone.2025.117567","DOIUrl":"10.1016/j.bone.2025.117567","url":null,"abstract":"<div><div>Histological analyses suggest that sclerostin inhibition increases bone mass primarily by stimulating modeling-based bone formation. However, clinical studies show that anti-resorptive therapies, which inhibit bone remodeling, blunt the anabolic effect of the anti-sclerostin antibody romosozumab. Moreover, suppressing remodeling inhibits bone formation in <em>Sost</em>-deficient mice. These latter studies suggest that bone remodeling is required for the full anabolic effect of sclerostin suppression. To address this, we suppressed bone remodeling in mice using the anti-RANKL antibody denosumab and then administered romosozumab, along with continued denosumab. Controls received either vehicle, denosumab alone, or romosozumab alone. The romosozumab-induced increase in bone was not blunted by denosumab. Similarly, the romosozumab-induced increases in osteoblast number and bone formation were not altered by denosumab. The anabolic effect of romosozumab was also not altered in a mouse model of rebound resorption caused by denosumab discontinuation. Nonetheless, denosumab reduced bone formation in Sost-deficient mice. These results demonstrate a striking difference in the dependence on bone remodeling for the anabolic effects of sclerostin suppression versus genetic inactivation of Sost and suggest distinct mechanisms drive osteoblast production in the two conditions. In addition, they suggest that the blunted response to romosozumab in clinical studies is not due to suppressed remodeling.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"199 ","pages":"Article 117567"},"PeriodicalIF":3.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the editor: “An analysis of 12 major fracture subtypes in adolescents and young adults: Global trends and population projections from GBD 2021”","authors":"Qiyuan Cheng","doi":"10.1016/j.bone.2025.117568","DOIUrl":"10.1016/j.bone.2025.117568","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"199 ","pages":"Article 117568"},"PeriodicalIF":3.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new BMP type 1 receptor kinase inhibitor for safe and efficient oral treatment to prevent genetically induced heterotopic ossification in mice","authors":"Jingwen Yang ,&nbsp;Haichun Pan ,&nbsp;Katsuhiko Sekimata ,&nbsp;Charles Hwang ,&nbsp;Anshul Kulkarni ,&nbsp;Hannah Thomas ,&nbsp;Jade Lindenau ,&nbsp;Tyler Duford ,&nbsp;Hiroki Ueharu ,&nbsp;Akiko Tanaka ,&nbsp;Naoki Sakai ,&nbsp;Mikako Shirouzu ,&nbsp;Yoshinobu Hashizume ,&nbsp;Benjamin Levi ,&nbsp;Hiroo Koyama ,&nbsp;Yuji Mishina","doi":"10.1016/j.bone.2025.117565","DOIUrl":"10.1016/j.bone.2025.117565","url":null,"abstract":"<div><div>Fibrodysplasia ossificans progressiva (FOP) is a rare genetic heterotopic ossification (HO) disorder that currently lacks a practical and definitive preventative approach. FOP is driven by gain-of-function variants in ACVR1, increasing dysregulated BMP signaling pathway, thus resulting in progressive and permanent replacement of skeletal muscle and connective tissues with heterotopic bone, ultimately leading to severe debilitation and premature death. Here, we describe the discovery of RK783, a small-molecule that inhibit BMP type 1 receptor kinase developed for treating FOP. This compound, the result of a rigorous process that involved screening approximately 140,000 compounds in silico with ligand-based structure followed by inhibitory activity and pharmacokinetics studies, offers a promising new direction in treating FOP. RK783 preferentially suppressed both basal and stimulated BMP-Smad1/5/9 signaling in vitro without affecting the signaling of Smad2/3. In vivo, the efficacy of RK783 was demonstrated using two FOP mice models, a conditional knock-in <em>ACVR1-R206H</em> and a transgenic <em>ACVR1-Q207D</em> mouse model, where oral dosing suppressed infiltration of immune cells and differentiation of fibroblast-adipose progenitor (FAP) cells, thus preventing ectopic cartilage and HO formation in muscles. Optimized dosing revealed that high and frequent treatment within the first couple of days after HO induction is critical to successfully suppress HO by RK738. These data suggest that RK783 can be used as an acute medication to prevent HO in FOP.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"199 ","pages":"Article 117565"},"PeriodicalIF":3.5,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of Zoledronate administration routes on the reproducibility of BRONJ in rodent models: A systematic review","authors":"Meircurius Dwi Condro Surboyo ,&nbsp;Prasiddha Mahardhika El Fadhlallah ,&nbsp;Yurie Sato-Yamada ,&nbsp;Kridtapat Sirisereephap ,&nbsp;Meiwen Fang ,&nbsp;Takeyasu Maeda ,&nbsp;Kei Tomihara ,&nbsp;Koichi Tabeta ,&nbsp;Nagako Yoshiba ,&nbsp;Andrea L. Rosenkranz ,&nbsp;Tomoki Maekawa","doi":"10.1016/j.bone.2025.117563","DOIUrl":"10.1016/j.bone.2025.117563","url":null,"abstract":"<div><h3>Objective</h3><div>Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a debilitating condition characterized by alveolar bone destruction associated with bisphosphonate medications, such as zoledronate. Zoledronate use is associated with an increased incidence of BRONJ. In rodent models, accurate replication of BRONJ stages depends on the route of zoledronate administration. This systematic review evaluates the reproducibility of BRONJ characteristics in rodent models by analyzing the effects of different zoledronate injection routes on clinical, histopathological, and radiological outcomes.</div></div><div><h3>Methods</h3><div>A systematic literature search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines using keywords related to BRONJ and zoledronate. The following data were collected from the selected studies: characteristics of mice and rats; zoledronate dose, duration, and route of administration. The BRONJ stage was determined in these studies based on clinical, histopathological, and radiological features of alveolar bone necrosis.</div></div><div><h3>Results</h3><div>Zoledronate treatment notably affected the reproducibility of BRONJ characteristics. Mice and rats exhibited distinct characteristics in producing BRONJ, depending on the route of zoledronate injection. Subcutaneous, intraperitoneal (IP), and intravenous (IV) injections in rats consistently produced exposed alveolar bone, the main criterion for clinical BRONJ. IP and IV zoledronate injection in mice produced a clinical BRONJ model. Neither mice nor rats exhibited differences in BRONJ characteristics according to sex.</div></div><div><h3>Conclusions</h3><div>Rodent models of BRONJ mimic the staging and characteristics of BRONJ observed in humans. Rat BRONJ models were more consistently reproducible when the zoledronate administration route was tailored to achieve specific research objectives.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"199 ","pages":"Article 117563"},"PeriodicalIF":3.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adolescents with long-duration type 1 diabetes have low bone mass and reduced levels of bone indices reflecting altered bone resorption","authors":"Diana Swolin-Eide ,&nbsp;Auste Pundziute Lyckå ,&nbsp;Daniel Novak ,&nbsp;Björn Andersson ,&nbsp;Gun Forsander ,&nbsp;Per Magnusson","doi":"10.1016/j.bone.2025.117560","DOIUrl":"10.1016/j.bone.2025.117560","url":null,"abstract":"<div><div>The prevalence of type 1 diabetes (T1D) is increasing globally and is associated with severe complications, including an increased risk of fractures. This case-control study investigated whether young individuals with well-controlled, long-duration T1D have differences in bone mass and bone biomarkers in comparison with healthy matched controls. Fifty individuals, aged 15.0–17.9 years, with a T1D duration of at least 8 years and (mean ± SD) 10.6 ± 2.1 years were included, hence the participants had diabetes throughout most part of their puberty and growth spurt. The mean HbA1c since diabetes diagnosis was 56 ± 6 mmol/mol (7.3 ± 0.6 %). Bone mass was assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography (pQCT). Clinical follow-up data were retrieved from the Swedish National Diabetes Registry. The control group comprised 50 healthy matched adolescents, aged 15.1–17.9 years. The groups were well-matched with no significant differences in age, sex, weight, height, body mass index and the self-reported physical activity. Total body less head aBMD and <em>Z</em>-scores were significantly lower in T1D individuals, <em>p</em> &lt; 0.05. Total tibia density and trabecular density, by pQCT, were also lower in the T1D group, <em>p</em> &lt; 0.05. There were no differences between the groups for parathyroid hormone, 25-hydroxyvitamin D, bone-specific alkaline phosphatase (BALP), intact procollagen type I N-propeptide (PINP), sclerostin, bioactive sclerostin and osteoprotegerin. However, individuals with T1D had reduced levels of C-terminal telopeptide of type I collagen (CTX) (<em>p</em> &lt; 0.001) and nuclear factor κB ligand (a.k.a. RANKL) (<em>p</em> = 0.01), indicating altered regulation of osteoclasts. In conclusion, young individuals with well-controlled, long-duration T1D have subnormal bone mass accrual, impaired microstructure at several sites and suppressed RANKL-mediated osteoclastogenesis resulting in reduced bone resorption. Based on these findings, we suggest that bone health should be monitored in pediatric diabetes care to potentially intervene early in life in susceptible individuals to achieve optimal peak bone mass.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"199 ","pages":"Article 117560"},"PeriodicalIF":3.5,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of denosumab on muscle health in older adults in long-term care","authors":"Nami Safai Haeri ,&nbsp;Subashan Perera ,&nbsp;Susan L. Greenspan","doi":"10.1016/j.bone.2025.117552","DOIUrl":"10.1016/j.bone.2025.117552","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcopenia, a condition characterized by the simultaneous presence of osteoporosis and sarcopenia, is a common geriatric syndrome associated with increased risk of falls and fracture. While there are multiple medications available for the management of osteoporosis, there are currently no approved pharmacological treatments for sarcopenia.</div></div><div><h3>Methods</h3><div>In this secondary analysis of a 2-year, double-blind, placebo-controlled, randomized trial involving 201 men and women with osteoporosis aged ≥65 years who were residents of long-term care communities (LTCCs), we examined the impact of denosumab on various indices of muscle health. Study participants received either denosumab 60 mg every 6 months or a matching placebo. We measured appendicular lean mass (ALM/Height²), lower extremity lean mass (LELM), grip strength, chair stand test performance, gait speed, Short Physical Performance Battery (SPPB), and total hip and spine bone density at baseline and at 6, 12, and 24 months.</div></div><div><h3>Results</h3><div>Our study involved 78 men and 123 women, with a mean age of 81.5 years. There were no statistically significant differences between the denosumab and placebo groups in terms of changes in appendicular lean mass adjusted for ALM/Height², LELM, chair stand performance, SPPB scores, or gait speed (all <em>p</em> &gt; 0.05). However, in women, the chair stand test and grip strength showed non-significant greater improvements with denosumab at 18 and 24 months, suggesting a potential positive effect.</div></div><div><h3>Conclusions</h3><div>We did not find confirmatory evidence that denosumab impacts muscle health in older adults residing in LTCCs, despite its clear advantages for improving bone density. We observed non-significant improvements in grip strength and chair stand test performance in women, which warrant further investigation.</div></div><div><h3>Mini abstract</h3><div>Our study found that in older adults in LTCCs, denosumab did not significantly enhance muscle health indices.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117552"},"PeriodicalIF":3.5,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144189960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodological concerns, implausibly early fracture reduction, and potential outcome misclassification: Comment on “Comparative effectiveness of romosozumab versus teriparatide for fracture prevention: A new-user, active comparator design”","authors":"Soichiro Masuda ,&nbsp;Toshiki Fukasawa ,&nbsp;Shuichi Matsuda ,&nbsp;Koji Kawakami","doi":"10.1016/j.bone.2025.117547","DOIUrl":"10.1016/j.bone.2025.117547","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"199 ","pages":"Article 117547"},"PeriodicalIF":3.5,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An analysis of 12 major fracture subtypes in adolescents and young adults: Global trends and population projections from GBD 2021","authors":"Haofeng Liang ,&nbsp;Yunliang Zhu ,&nbsp;Baoliang Lu ,&nbsp;Chenxi Zhao ,&nbsp;Kunpeng Ding ,&nbsp;Meiling Shi ,&nbsp;Xiaolong Chen ,&nbsp;Qingfa Guo ,&nbsp;Sikuan Zheng ,&nbsp;Jianye Tan","doi":"10.1016/j.bone.2025.117551","DOIUrl":"10.1016/j.bone.2025.117551","url":null,"abstract":"<div><h3>Background</h3><div>Fractures represent a significant global public health concern, particularly affecting younger and older populations; however, there is a notable lack of comprehensive epidemiological research focusing on fracture among adolescents and young adults (AYAs).</div></div><div><h3>Methods</h3><div>We assessed the fracture burden in AYAs using GBD 2021 data. Concentration curves and indices were used to evaluate socioeconomic inequalities. Trends and projections were estimated using Bayesian age-period-cohort (BAPC) models.</div></div><div><h3>Results</h3><div>In 2021, the global incidence of fractures among AYAs reached 40.77 million cases, corresponding to an age-standardized incidence rate (ASR) of 2156 per 100,000 population. Compared to all ages, AYAs showed a higher proportion of Fracture of hand (wrist and other distal part of hand) and Fracture of foot bones except ankle (Hand/Wrist Fx and Foot Fx), while Fracture of hip and Fracture of femur, other than femoral neck (Hip Fx and Femur Shaft Fx) were less frequent but contributed disproportionately to disability. Fracture of patella, tibia or fibula, or ankle (Lower Leg Fx) ranked first in all indicators, contributing over 70 % of Years lived with disability (YLDs) in some regions. Fracture of radius and/or ulna (Forearm Fx) ranked second in incidence but had limited YLDs impact. Fracture of pelvis (Pelvic Fx) caused substantial disability despite lower frequency. Girls aged 10–14 were the only group projected to experience a rising burden.</div></div><div><h3>Conclusions</h3><div>Despite an overall decline since 1990, the fracture burden in AYAs remains significant, particularly in high-SDI and conflict regions. Distinct fracture patterns in AYAs highlight the need for age-specific prevention strategies focusing on high-incidence and high-disability subtypes.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"199 ","pages":"Article 117551"},"PeriodicalIF":3.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related differences in bone structural parameters using 3D-DXA and TBS in men and women: The Bunkyo Health Study","authors":"Hikaru Otsuka ,&nbsp;Hiroki Tabata ,&nbsp;Naoaki Ito ,&nbsp;Huicong Shi ,&nbsp;Takahito Iwashimizu ,&nbsp;Hideyoshi Kaga ,&nbsp;Yuki Someya ,&nbsp;Hitoshi Naito ,&nbsp;Abulaiti Abudurezake ,&nbsp;Saori Kakehi ,&nbsp;Yasuyo Yoshizawa ,&nbsp;Muneaki Ishijima ,&nbsp;Ryuzo Kawamori ,&nbsp;Hirotaka Watada ,&nbsp;Yoshifumi Tamura","doi":"10.1016/j.bone.2025.117549","DOIUrl":"10.1016/j.bone.2025.117549","url":null,"abstract":"<div><h3>Background</h3><div>Recent advancements in imaging technology, including trabecular bone score (TBS) and 3D-DXA, enable comprehensive bone structure assessment beyond traditional bone mineral density (BMD) measurements in osteoporosis. However, age-related differences in bone structure remain unclear.</div></div><div><h3>Method</h3><div>Using data from the Bunkyo Health Study, we analyzed bone structural parameters in 1372 participants (662 men, 710 women) for the proximal femur and 1053 participants (500 men, 553 women) for the lumbar spine, aged 65–84 years. Parameters included TBS of the lumbar spine and proximal femur measurements (3D-Shaper), including volumetric BMD of trabecular, cortical, and integral, cortical thickness, and surface BMD in each bone region. Age group comparisons (65–69, 70–74, 75–79, and 80–84 years) were performed using Kruskal–Wallis test with Bonferroni correction.</div></div><div><h3>Results</h3><div>In men, only cortical thickness significantly decreased in the proximal femur regions, particularly in the 80–84 age group compared to the 65–69 and 70–74 age groups (−2.3 %, <em>P</em> &lt; 0.05). In women, all parameters significantly decreased (<em>P</em> &lt; 0.001), especially in the 80–84 age group—cortical thickness (−3.9 %), cortical surface BMD (−9.6 %), cortical volumetric BMD (−4.0 %), and trabecular volumetric BMD (−8.4 %)—compared to the 65–69 age group. TBS was significantly lower in women aged 70–74 and 80–84 years compared to those aged 65–69 years (<em>P</em> &lt; 0.001); however, no significant changes were observed in men.</div></div><div><h3>Conclusions</h3><div>Women showed widespread changes across all parameters, whereas men exhibited primarily cortical thickness changes, suggesting the need for sex-specific approaches for osteoporosis assessment and fracture risk prediction.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"199 ","pages":"Article 117549"},"PeriodicalIF":3.5,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}