Pub Date : 2025-11-16DOI: 10.1016/j.bone.2025.117731
Rongjie Lin , Yiqing Huang , Zhenbin Chen , Xi Zeng , Yao Wang , Shaohuang Weng , Yu Cheng , Min Chen
Osteomyelitis (OM) is a severe bone-destructive disease characterized by infection and inflammation. Transcriptomic analysis of datasets GSE18043 and GSE30119 identified CTLA4 as a key regulator associated with immune modulation and osteogenic differentiation. Subsequent bioinformatic and immune infiltration analyses revealed that CTLA4 expression correlated with increased anti-inflammatory macrophage infiltration and activation of the Wnt/β-catenin signaling pathway of osteoblasts. Functionally, CTLA4-Ig promoted osteogenic differentiation, enhanced matrix mineralization, and upregulated osteogenic markers in MC3T3-E1 cells, while concurrently inhibiting osteoclast formation and bone resorption activity. In a Staphylococcus aureus-induced rat OM model, histological and immunohistochemical analyses further confirmed enhanced osteoblast activity and reduced osteoclast presence in the CTLA4-Ig treated group. CTLA4-Ig administration preserved bone structural integrity by modulating the inflammatory microenvironment, characterized by reduced expression of pro-inflammatory cytokines, increased levels of anti-inflammatory cytokines, enhanced osteogenic regeneration, and a reduction in bacterial burden. Collectively, these findings established CTLA4-Ig as a dual-action modulator that promoted bone regeneration while inhibiting bone destruction, offering a promising therapeutic strategy for OM.
{"title":"CTLA4-Ig sustains osteogenic potential and inhibits osteoclastogenesis in Staphylococcus aureus osteomyelitis","authors":"Rongjie Lin , Yiqing Huang , Zhenbin Chen , Xi Zeng , Yao Wang , Shaohuang Weng , Yu Cheng , Min Chen","doi":"10.1016/j.bone.2025.117731","DOIUrl":"10.1016/j.bone.2025.117731","url":null,"abstract":"<div><div>Osteomyelitis (OM) is a severe bone-destructive disease characterized by infection and inflammation. Transcriptomic analysis of datasets GSE18043 and GSE30119 identified CTLA4 as a key regulator associated with immune modulation and osteogenic differentiation. Subsequent bioinformatic and immune infiltration analyses revealed that CTLA4 expression correlated with increased anti-inflammatory macrophage infiltration and activation of the Wnt/β-catenin signaling pathway of osteoblasts. Functionally, CTLA4-Ig promoted osteogenic differentiation, enhanced matrix mineralization, and upregulated osteogenic markers in MC3T3-E1 cells, while concurrently inhibiting osteoclast formation and bone resorption activity. In a <em>Staphylococcus aureus</em>-induced rat OM model, histological and immunohistochemical analyses further confirmed enhanced osteoblast activity and reduced osteoclast presence in the CTLA4-Ig treated group. CTLA4-Ig administration preserved bone structural integrity by modulating the inflammatory microenvironment, characterized by reduced expression of pro-inflammatory cytokines, increased levels of anti-inflammatory cytokines, enhanced osteogenic regeneration, and a reduction in bacterial burden. Collectively, these findings established CTLA4-Ig as a dual-action modulator that promoted bone regeneration while inhibiting bone destruction, offering a promising therapeutic strategy for OM.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117731"},"PeriodicalIF":3.6,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145552097","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}
Pub Date : 2025-11-15DOI: 10.1016/j.bone.2025.117730
Christina J. Alexander , Heather M. Macdonald , Heather A. McKay , Leigh Gabel
Bone adapts to its loading environment throughout the lifespan, with rapid gains during adolescence. Accelerometers are commonly used to measure physical activity (PA) and examine its associations with bone outcomes; however, common approaches reduce high-resolution data to a few metrics (e.g., minutes per day (min/d) in various activity intensities). In this observational cohort study, we investigated whether using new accelerometry metrics to synthesize count-based accelerometry data would explain relationships between PA and estimated bone strength accrual. Four years of longitudinal data from over 300 children and adolescents in the Healthy Bones Study III were used to examine associations between the accelerometer-derived intensity gradient (IG) and daily impact score (DIS) with estimated bone strength (failure load, N; 8 % site of the distal tibia) as measured with high-resolution peripheral quantitative computed tomography. We also explored whether associations were independent of a traditional metric of min/d of vigorous physical activity (VPA). In linear mixed effects models, IG was not associated with bone strength independent of VPA ( = −515.2 (−1302.1, 270.4), p = 0.20; = 25.5 (14.0, 37.0), p < 0.001), but DIS was positively associated with bone strength independent of VPA ( = 25.2 (7.0, 43.6), p = 0.007; = 3.2 (−6.1, 1.4), p = 0.67). Our findings suggest that the DIS may be a more appropriate metric for evaluating accelerometry data in relation to adolescent bone strength accrual compared with traditional duration (minutes of PA per day) metrics.
骨骼在整个生命周期中适应其负载环境，在青春期迅速增长。加速度计通常用于测量身体活动（PA）并检查其与骨骼结果的关系；然而，常见的方法将高分辨率数据减少到几个指标（例如，在各种活动强度下，每天分钟数（min/d））。在这项观察性队列研究中，我们研究了使用新的加速度测量指标来合成基于计数的加速度测量数据是否可以解释PA与估计骨强度累积之间的关系。健康骨骼研究III中超过300名儿童和青少年的四年纵向数据被用来检验加速度计衍生的强度梯度（IG）和每日冲击评分（DIS）与估计骨强度（失效负荷，N； 8 %胫骨远端部位）之间的关系，这些数据是用高分辨率外周定量计算机断层扫描测量的。我们还探讨了这种关联是否独立于剧烈身体活动（VPA）的最小/天的传统度量。在线性混合效应模型中，IG与骨强度无关，与VPA无关(βIG = -515.2 (-1302.1, 270.4), p = 0.20；βVPA = 25.5 (14.0, 37.0), p 说= 25.2 (7.0,43.6),p = 0.007;βVPA= 3.2 (-6.1, 1.4), p = 0.67)。我们的研究结果表明，与传统的持续时间（每天PA分钟）指标相比，DIS可能是评估与青少年骨强度累积相关的加速度测量数据更合适的指标。
{"title":"Accelerometer-derived daily impact score is positively associated with bone strength accrual during adolescence","authors":"Christina J. Alexander , Heather M. Macdonald , Heather A. McKay , Leigh Gabel","doi":"10.1016/j.bone.2025.117730","DOIUrl":"10.1016/j.bone.2025.117730","url":null,"abstract":"<div><div>Bone adapts to its loading environment throughout the lifespan, with rapid gains during adolescence. Accelerometers are commonly used to measure physical activity (PA) and examine its associations with bone outcomes; however, common approaches reduce high-resolution data to a few metrics (e.g., minutes per day (min/d) in various activity intensities). In this observational cohort study, we investigated whether using new accelerometry metrics to synthesize count-based accelerometry data would explain relationships between PA and estimated bone strength accrual. Four years of longitudinal data from over 300 children and adolescents in the Healthy Bones Study III were used to examine associations between the accelerometer-derived intensity gradient (IG) and daily impact score (DIS) with estimated bone strength (failure load, N; 8 % site of the distal tibia) as measured with high-resolution peripheral quantitative computed tomography. We also explored whether associations were independent of a traditional metric of min/d of vigorous physical activity (VPA). In linear mixed effects models, IG was not associated with bone strength independent of VPA (<span><math><msub><mi>β</mi><mi>IG</mi></msub></math></span> = −515.2 (−1302.1, 270.4), <em>p</em> = 0.20; <span><math><msub><mi>β</mi><mi>VPA</mi></msub><mspace></mspace></math></span>= 25.5 (14.0, 37.0), <em>p</em> < 0.001), but DIS was positively associated with bone strength independent of VPA (<span><math><msub><mi>β</mi><mi>DIS</mi></msub></math></span> = 25.2 (7.0, 43.6), <em>p</em> = 0.007; <span><math><msub><mi>β</mi><mi>VPA</mi></msub><mspace></mspace></math></span>= 3.2 (−6.1, 1.4), <em>p</em> = 0.67). Our findings suggest that the DIS may be a more appropriate metric for evaluating accelerometry data in relation to adolescent bone strength accrual compared with traditional duration (minutes of PA per day) metrics.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117730"},"PeriodicalIF":3.6,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145544026","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}
Pub Date : 2025-11-14DOI: 10.1016/j.bone.2025.117721
Yuchen Lou , Xuan Liu , Chenxiao Ma , Xin Liu
Background
This study aimed to evaluate the diagnostic value of special AT-rich sequence binding protein 2 (SATB2) in distinguishing between osteogenic tumors and non-osteogenic tumors, providing reliable scientific evidence for its use as an adjunct diagnostic tool in clinical practice.
Methods
We conducted systematic searches of the PubMed, EMBASE, Cochrane Library, and Web of Science databases to identify all relevant literature published up to June 2025 that studied SATB2 in the differential diagnosis between osteogenic and non-osteogenic tumors. The QUADAS-2 tool was used to evaluate the methodological quality of each included study. Meta-analysis was performed using STATA SE-64 and RevMan 5.4 software.
Results
10 studies involving a total of 1234 cases were included, comprising 494 patients with osteogenic tumors and 740 patients with non-osteogenic tumors. The pooled sensitivity and specificity of SATB2 for differentiating osteogenic from non-osteogenic tumors were 0.97 (95 % CI: 0.90–0.99) and 0.88 (95 % CI: 0.73–0.96), respectively. The PLR was 8.17 (95 % CI: 3.30–20.23), and the NLR was 0.03 (95 % CI: 0.01–0.12). The DOR was 252.82 (95 % CI: 41.85–1527.16). The AUC was 0.98 (95 % CI: 0.97–0.99).
Conclusion
SATB2 demonstrates high sensitivity and robust specificity as an adjunct diagnostic marker for differentiating osteogenic from non-osteogenic tumors. However, it should be noted that this study excluded tumors with ambiguous definitions, such as giant cell tumors of bone. Future research should further validate the clinical utility of SATB2 in these and other challenging lesions.
{"title":"The diagnostic utility of SATB2 immunohistochemistry as an adjunct for differentiating osteogenic from non-osteogenic bone tumors: A systematic review and Meta-analysis","authors":"Yuchen Lou , Xuan Liu , Chenxiao Ma , Xin Liu","doi":"10.1016/j.bone.2025.117721","DOIUrl":"10.1016/j.bone.2025.117721","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to evaluate the diagnostic value of special AT-rich sequence binding protein 2 (SATB2) in distinguishing between osteogenic tumors and non-osteogenic tumors, providing reliable scientific evidence for its use as an adjunct diagnostic tool in clinical practice.</div></div><div><h3>Methods</h3><div>We conducted systematic searches of the PubMed, EMBASE, Cochrane Library, and Web of Science databases to identify all relevant literature published up to June 2025 that studied SATB2 in the differential diagnosis between osteogenic and non-osteogenic tumors. The QUADAS-2 tool was used to evaluate the methodological quality of each included study. Meta-analysis was performed using STATA SE-64 and RevMan 5.4 software.</div></div><div><h3>Results</h3><div>10 studies involving a total of 1234 cases were included, comprising 494 patients with osteogenic tumors and 740 patients with non-osteogenic tumors. The pooled sensitivity and specificity of SATB2 for differentiating osteogenic from non-osteogenic tumors were 0.97 (95 % CI: 0.90–0.99) and 0.88 (95 % CI: 0.73–0.96), respectively. The PLR was 8.17 (95 % CI: 3.30–20.23), and the NLR was 0.03 (95 % CI: 0.01–0.12). The DOR was 252.82 (95 % CI: 41.85–1527.16). The AUC was 0.98 (95 % CI: 0.97–0.99).</div></div><div><h3>Conclusion</h3><div>SATB2 demonstrates high sensitivity and robust specificity as an adjunct diagnostic marker for differentiating osteogenic from non-osteogenic tumors. However, it should be noted that this study excluded tumors with ambiguous definitions, such as giant cell tumors of bone. Future research should further validate the clinical utility of SATB2 in these and other challenging lesions.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117721"},"PeriodicalIF":3.6,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145535107","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}
Pub Date : 2025-11-13DOI: 10.1016/j.bone.2025.117729
Weiming Xie , Xiaozhou Bai , Miao Liu , Haonan Shangguan , Ying Zhan , Xiaodan Wu , Wei Zhang , Yusong Pei , Guoxu Zhang , Zhiguo Wang , Zhaomin Yao
Bone metastasis, a frequent complication of advanced cancers, requires early, precise detection to enable timely interventions and improve patient outcomes. Computed tomography (CT), valued for non-invasive, high-resolution imaging, is essential for identifying bone metastatic lesions. However, these small, morphologically diverse, low-contrast lesions, combined with complex tumor microenvironments and computational limitations, challenge deep learning models' accuracy and real-time applicability. We propose BM-DETR, a Transformer-based model integrating spatial-contextual enhancement module (SCEM) to enhance low-contrast lesion features through channel attention and spatial mixing, AttentionUpsample for superior multi-scale feature fusion via dual-branch upsampling, and dilated transformer attention block (DTAB) to improve contextual modeling, addressing transformer limitations in local detail capture while optimizing efficiency. Evaluated on OsteoScan dataset, BM-DETR achieves mAP50 of 0.9376, and on BMSeg dataset, mAP50 of 0.9139, surpassing state-of-the-art methods. Balancing high accuracy with computational efficiency, BM-DETR's potential for edge deployment supports early screening and intelligent diagnosis of bone metastases. This work provides a robust foundation for automated lesion detection, advancing clinical translation of diagnostic systems.
{"title":"Transformer-based multi-scale feature fusion for real-time CT bone metastasis detection","authors":"Weiming Xie , Xiaozhou Bai , Miao Liu , Haonan Shangguan , Ying Zhan , Xiaodan Wu , Wei Zhang , Yusong Pei , Guoxu Zhang , Zhiguo Wang , Zhaomin Yao","doi":"10.1016/j.bone.2025.117729","DOIUrl":"10.1016/j.bone.2025.117729","url":null,"abstract":"<div><div>Bone metastasis, a frequent complication of advanced cancers, requires early, precise detection to enable timely interventions and improve patient outcomes. Computed tomography (CT), valued for non-invasive, high-resolution imaging, is essential for identifying bone metastatic lesions. However, these small, morphologically diverse, low-contrast lesions, combined with complex tumor microenvironments and computational limitations, challenge deep learning models' accuracy and real-time applicability. We propose BM-DETR, a Transformer-based model integrating spatial-contextual enhancement module (SCEM) to enhance low-contrast lesion features through channel attention and spatial mixing, AttentionUpsample for superior multi-scale feature fusion via dual-branch upsampling, and dilated transformer attention block (DTAB) to improve contextual modeling, addressing transformer limitations in local detail capture while optimizing efficiency. Evaluated on OsteoScan dataset, BM-DETR achieves mAP50 of 0.9376, and on BMSeg dataset, mAP50 of 0.9139, surpassing state-of-the-art methods. Balancing high accuracy with computational efficiency, BM-DETR's potential for edge deployment supports early screening and intelligent diagnosis of bone metastases. This work provides a robust foundation for automated lesion detection, advancing clinical translation of diagnostic systems.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117729"},"PeriodicalIF":3.6,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145531042","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}
Pub Date : 2025-11-11DOI: 10.1016/j.bone.2025.117728
Lewis Weeda , Saiuj Bhat , Katie Wang , Ben Chia , Nick Calvert , Hannah Seymour , Revathy Manickavasagar , Lucy Kilshaw
Aims
Hip fracture patients have significant morbidity and mortality, with worse outcomes in end-stage kidney disease (ESKD) patients receiving dialysis. This study evaluates and quantifies the risk of mortality and complications in dialysis patients undergoing surgery for hip fractures.
Methods
A systematic review of studies investigating complications after surgery for hip fractures in ESKD patients receiving dialysis was performed across various databases. Mortality (30-day or longer) was the primary outcome.
Results
Thirty studies encompassing 23,024 dialysis patients were included, most of which had a low risk of bias (n = 26; 87 %). Thirty-day (RR 2.2; CI 95 %: 1.5, 3.2 and HR 2.3; CI 95 %: 1.7, 3.0) and overall mortality (RR 1.9; CI 95 %: 1.6, 2.2) were two-fold greater in dialysis patients. There was also an increased risk of surgical site infection (RR 1.6. CI 95 %: 1.3, 2.0), major adverse cardiac events (RR 1.9. CI 95 %: 1.3, 3.0), and sepsis (RR 1.9. CI: 1.5, 2.2) in this cohort compared to a non-dialysis cohort.
Conclusion
Patients receiving dialysis experience approximately two-fold greater mortality after hip fracture surgery compared to patients not receiving dialysis. Dialysis patients face higher rates of complications after surgery, notably wound infection, major adverse cardiac events, and sepsis. Results from this study provide quantitative estimates for perioperative counselling of patients alongside families. While some tools aid in predicting post-operative outcomes, further research may refine risk stratification in this cohort. Additional evidence is required to establish evidence-based models of care that optimise the peri-operative health of dialysis patients.
目的：髋部骨折患者具有显著的发病率和死亡率，终末期肾病（ESKD）患者接受透析治疗的预后更差。本研究评估和量化透析患者髋部骨折手术的死亡率和并发症的风险。方法：通过不同的数据库对接受透析的ESKD患者髋部骨折术后并发症的研究进行系统回顾。死亡率（30天或更长）是主要结局。结果：纳入了30项研究，包括23,024例透析患者，其中大多数具有低偏倚风险（n = 26;87 %）。透析患者的30天死亡率（RR 2.2; CI 95 %:1.5,3.2和HR 2.3; CI 95 %:1.7,3.0）和总死亡率（RR 1.9; CI 95 %:1.6,2.2）高出两倍。手术部位感染的风险也增加（RR为1.6）。CI 95 %:1.3,2.0)，主要心脏不良事件（RR 1.9）。CI 95 %:1.3,3.0)和脓毒症(RR 1.9。CI: 1.5, 2.2)，与非透析组相比。结论：与未接受透析的患者相比，接受透析的患者髋部骨折术后死亡率大约高出两倍。透析患者术后并发症发生率较高，特别是伤口感染、主要心脏不良事件和败血症。本研究的结果为患者及其家属围手术期咨询提供了定量估计。虽然一些工具有助于预测术后结果，但进一步的研究可能会完善该队列的风险分层。需要更多的证据来建立循证护理模式，以优化透析患者的围手术期健康。
{"title":"Complications following hip fracture surgery in end-stage kidney disease patients receiving dialysis: A systematic review and meta-analysis of cohort studies","authors":"Lewis Weeda , Saiuj Bhat , Katie Wang , Ben Chia , Nick Calvert , Hannah Seymour , Revathy Manickavasagar , Lucy Kilshaw","doi":"10.1016/j.bone.2025.117728","DOIUrl":"10.1016/j.bone.2025.117728","url":null,"abstract":"<div><h3>Aims</h3><div>Hip fracture patients have significant morbidity and mortality, with worse outcomes in end-stage kidney disease (ESKD) patients receiving dialysis. This study evaluates and quantifies the risk of mortality and complications in dialysis patients undergoing surgery for hip fractures.</div></div><div><h3>Methods</h3><div>A systematic review of studies investigating complications after surgery for hip fractures in ESKD patients receiving dialysis was performed across various databases. Mortality (30-day or longer) was the primary outcome.</div></div><div><h3>Results</h3><div>Thirty studies encompassing 23,024 dialysis patients were included, most of which had a low risk of bias (<em>n</em> = 26; 87 %). Thirty-day (RR 2.2; CI 95 %: 1.5, 3.2 and HR 2.3; CI 95 %: 1.7, 3.0) and overall mortality (RR 1.9; CI 95 %: 1.6, 2.2) were two-fold greater in dialysis patients. There was also an increased risk of surgical site infection (RR 1.6. CI 95 %: 1.3, 2.0), major adverse cardiac events (RR 1.9. CI 95 %: 1.3, 3.0), and sepsis (RR 1.9. CI: 1.5, 2.2) in this cohort compared to a non-dialysis cohort.</div></div><div><h3>Conclusion</h3><div>Patients receiving dialysis experience approximately two-fold greater mortality after hip fracture surgery compared to patients not receiving dialysis. Dialysis patients face higher rates of complications after surgery, notably wound infection, major adverse cardiac events, and sepsis. Results from this study provide quantitative estimates for perioperative counselling of patients alongside families. While some tools aid in predicting post-operative outcomes, further research may refine risk stratification in this cohort. Additional evidence is required to establish evidence-based models of care that optimise the peri-operative health of dialysis patients.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117728"},"PeriodicalIF":3.6,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515262","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}
Achondroplasia (ACH), a skeletal dysplasia, is characterized by disproportionate short stature and impaired quality of life. In Japan, growth hormone (GH) therapy has been available since 1997, and vosoritide, a C-type natriuretic peptide analog, was approved in 2022. Although clinical trials have demonstrated vosoritide's efficacy, real-world comparative data in Japan are scarce. We conducted a retrospective study of 22 children with ACH treated with vosoritide for over 6 months at a single institution between February 2018 and May 2025. Patients were divided into two groups: GH-naïve group (Group A, n = 13), receiving vosoritide alone, and a switch group (Group B, n = 9), who transitioned from prior GH treatment. Growth outcomes included annualized growth velocity (AGV) and height standard deviation scores (HT-SDS) calculated using Japanese and ACH-specific (HT-SDS_ACH) references. Group A (median age: 2.10 years) demonstrated significant improvements in HT-SDS_ACH at years 3 (p = 0.0022), 4 (p = 0.0004), 5 (p = 0.007), and 6 (p = 0.0012). Group B (median age: 10.1 years), with a median of 6.10 years of GH exposure, showed significant increases at 1 year (p = 0.047) and 2.5 years (p = 0.0054) after switching. In Group B, HT-SDS_ACH remained stable among patients starting vosoritide before age 4, but improved significantly in those beginning later. Injection site pain occurred in three patients, leading to one discontinuation. Vosoritide improves linear growth in children with ACH, including those previously treated with GH, showing greater benefit when started at ≥4 years, though earlier use may offer advantages.
{"title":"Real-world safety and age-dependent effectiveness of vosoritide in achondroplasia: A single-center retrospective analysis of transition from growth hormone to vosoritide","authors":"Takaaki Shimada , Hirofumi Nakayama , Ikumi Ueda , Takeshi Ishimi , Chieko Yamada , Yukako Nakano , Kenichi Yamamoto , Makoto Fujiwara , Taichi Kitaoka , Keiichi Ozono , Takuo Kubota , Yasuhisa Ohata , Yasuji Kitabatake","doi":"10.1016/j.bone.2025.117722","DOIUrl":"10.1016/j.bone.2025.117722","url":null,"abstract":"<div><div>Achondroplasia (ACH), a skeletal dysplasia, is characterized by disproportionate short stature and impaired quality of life. In Japan, growth hormone (GH) therapy has been available since 1997, and vosoritide, a C-type natriuretic peptide analog, was approved in 2022. Although clinical trials have demonstrated vosoritide's efficacy, real-world comparative data in Japan are scarce. We conducted a retrospective study of 22 children with ACH treated with vosoritide for over 6 months at a single institution between February 2018 and May 2025. Patients were divided into two groups: GH-naïve group (Group A, <em>n</em> = 13), receiving vosoritide alone, and a switch group (Group B, <em>n</em> = 9), who transitioned from prior GH treatment. Growth outcomes included annualized growth velocity (AGV) and height standard deviation scores (HT-SDS) calculated using Japanese and ACH-specific (HT-SDS_ACH) references. Group A (median age: 2.10 years) demonstrated significant improvements in HT-SDS_ACH at years 3 (<em>p</em> = 0.0022), 4 (<em>p</em> = 0.0004), 5 (<em>p</em> = 0.007), and 6 (<em>p</em> = 0.0012). Group B (median age: 10.1 years), with a median of 6.10 years of GH exposure, showed significant increases at 1 year (<em>p</em> = 0.047) and 2.5 years (<em>p</em> = 0.0054) after switching. In Group B, HT-SDS_ACH remained stable among patients starting vosoritide before age 4, but improved significantly in those beginning later. Injection site pain occurred in three patients, leading to one discontinuation. Vosoritide improves linear growth in children with ACH, including those previously treated with GH, showing greater benefit when started at ≥4 years, though earlier use may offer advantages.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117722"},"PeriodicalIF":3.6,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145515251","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}
Pub Date : 2025-11-11DOI: 10.1016/j.bone.2025.117718
Suying Zhu , Doudou Hao , Yanli Chen , Zhiyou Shi , Yang Zhong , Fengying Zhang , Feng Tang , Suyuan Wang , Yunhong Wu
High-altitude hypoxia disrupts bone metabolic homeostasis and accelerates bone loss. However, effective strategies for preventing and treating hypoxia-induced osteoporosis remain limited. This study aimed to evaluate the protective effects of hydrogen-rich water (HRW) and coral calcium hydride (CCH) against bone degeneration and multi-organ injury in a mouse model of chronic hypoxic exposure. Mice exposed to a hypoxic environment simulating 5500 m altitude for 4 months showed progressive bone deterioration from prolonged hypoxic exposure, which was significantly ameliorated by HRW intervention. Hydrogen intervention also markedly attenuated hypoxia-induced inflammation and damage in multiple organs such as the liver, lungs, kidneys, and colon. Hypoxia exposure led to changes in the diversity of gut microbiota, along with a decrease in the abundance of aerobic bacteria and beneficial bacteria (e.g., Lactobacillus), while hydrogen intervention could partially reverse this dysbiosis. At the molecular level, hypoxia significantly up-regulated the expression of HIF-1α, RANKL, and TRAP in bone tissue, and suppressed Nrf2 protein levels. However, hydrogen intervention did not directly alter the expression of these molecules. Hydrogen intervention may exert a bone-protective effect through the “gut-bone axis” by regulating the homeostasis of gut microbiota and alleviating systemic inflammation and oxidative stress, rather than directly acting on the classical hypoxia signaling pathway. Therefore, hydrogen intervention is a potential strategy to alleviate chronic hypoxia-induced bone loss and multi-organ damage by regulating gut microbiota homeostasis, which provides new insights and directions for the prevention and treatment of high-altitude bone-related diseases.
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