Bone最新文献

{"title":"Angiotensin receptor blockers (ARBs) but not angiotensin converting enzyme inhibitors (ACE-Is) are associated with lower osteoclast activity and higher bone mineral density: Results from the TUDA study","authors":"Donal Fitzpatrick ,&nbsp;Eamon Laird ,&nbsp;Mary Ward ,&nbsp;Leane Hoey ,&nbsp;Catherine F. Hughes ,&nbsp;Liadhan McAnena ,&nbsp;J.J. Strain ,&nbsp;Conal Cunningham ,&nbsp;Anne M. Molloy ,&nbsp;Helene McNulty ,&nbsp;Rosaleen Lannon ,&nbsp;Kevin McCarroll","doi":"10.1016/j.bone.2025.117710","DOIUrl":"10.1016/j.bone.2025.117710","url":null,"abstract":"<div><h3>Introduction</h3><div>The renin-angiotensin system (RAS) is implicated in osteoclast activation and bone loss. We investigated the relationship of angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACE-Is) usage with bone turnover markers (BTM) and bone mineral density (BMD).</div></div><div><h3>Methods</h3><div>Participants were from the TUDA cohort of Irish adults aged ≥60 years not receiving osteoporosis treatment. BMD at the total hip, femoral neck and lumbar spine, and BTMs were compared between users of ARBs or ACE-Is and non-users of either medication, adjusting for age, sex, BMI, Timed-Up-and-Go, vitamin D status, eGFR, parathyroid hormone, lifestyle factors, socioeconomic status, comorbidities and other medications.</div></div><div><h3>Results</h3><div>In the ARB analysis (<em>n</em> = 1516; mean age 70.2 years; 64 % female; 33 % users), ARB use vs non-use was associated with higher adjusted BMD at the femoral neck 0.856 g/cm² (95 % CI 0.830–0.882) vs 0.837 (0.812–0.863), <em>p</em> = 0.005; total hip 0.937 g/cm² (0.909–0.965) vs 0.913 (0.886–0.941), <em>p</em> = 0.002; and lumbar spine 1.122 g/cm² (1.082–1.162) vs 1.087 (1.047–1.126), <em>p</em> &lt; 0.001. In the ACE-I analysis (<em>n</em> = 1692; mean age 70.1 years; 59 % female; 40 % users), ACE-I usage was not associated with BMD. In a subsample with available BTM (<em>n</em> = 1613), ARB users versus non-users had lower serum adjusted tartrate-resistant acid phosphatase 3.14 units/l (2.87–3.41) vs 3.28 (3.01–3.55), <em>p</em> = 0.040. No association was found between ACE-I usage and TRACP5b.</div></div><div><h3>Discussion</h3><div>ARB use was associated with higher BMD and lower TRACP5b, a marker of osteoclast activity, with no corresponding associations for ACE-Is. This pattern suggests a possible differential effect between ARBs and ACE-Is on bone that merits evaluation in prospective cohorts and randomised trials.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117710"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145464740","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":"Effects of exercise on the cortical bone of the proximal femur in women: a systematic review and meta-analysis","authors":"Norifumi Fujii ,&nbsp;Takeshi Imura ,&nbsp;Tsubasa Mitsutake ,&nbsp;Kenta Hirohama ,&nbsp;Nobukazu Okimoto ,&nbsp;Manabu Tsukamoto ,&nbsp;Ryo Tanaka","doi":"10.1016/j.bone.2025.117740","DOIUrl":"10.1016/j.bone.2025.117740","url":null,"abstract":"<div><h3>Objective</h3><div>The incidence of hip fractures is higher in women. Thus, preventive interventions (e.g., exercise) are important. According to research, the strength of the proximal femur, which affects hip fractures, is more important in the cortical bone than in the cancellous bone. This study aimed to evaluate the presence and quality of evidence of exercise on the cortical bone of the proximal femur in women.</div></div><div><h3>Methods</h3><div>A literature search was performed using the following databases: PubMed, Physiotherapy Evidence Database, Cochrane Central Register of Controlled Trials, and Scopus. Six articles that met the inclusion and exclusion criteria were selected for systematic review and meta-analysis.</div></div><div><h3>Results</h3><div>Only one study included premenopausal women, and the meta-analysis was performed only on studies in postmenopausal women. Exercise significantly improved the femoral neck cortical thickness in postmenopausal women (I² = 82 %, <em>p</em> &lt; 0.01; random-effects model standardized mean difference [SMD] = 0.61 [95 % confidence interval {CI}: 0.07–1.15]). However, it did not significantly improve the femoral neck cross-sectional area (I² = 95 %, <em>p</em> &lt; 0.01; random-effects model SMD = 0.72 [95 % CI: −0.43–1.87]).</div></div><div><h3>Conclusion</h3><div>The meta-analysis revealed that high-intensity resistance training combined with high-impact training for 8 months or more improved the femoral neck cortical thickness in postmenopausal women.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117740"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620867","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 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 ,&nbsp;Xuan Liu ,&nbsp;Chenxiao Ma ,&nbsp;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":"2026-02-01","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}

{"title":"Association of metabolic score for visceral fat with fragility fracture risk: The combined and mediating roles of arterial stiffness","authors":"Lu Guo ,&nbsp;Shaoxuan Wei ,&nbsp;Qian Liu ,&nbsp;Wenqi Xu ,&nbsp;Guodong Wang ,&nbsp;Wenchao Yao ,&nbsp;Nan Zhang ,&nbsp;Man Gui ,&nbsp;Xiaoli Hou ,&nbsp;Shuohua Chen ,&nbsp;Bin Wang ,&nbsp;Xinhao Fan ,&nbsp;Liu Zhang ,&nbsp;Jingyuan Gao ,&nbsp;Lei Xing ,&nbsp;Shouling Wu ,&nbsp;Faming Tian","doi":"10.1016/j.bone.2025.117739","DOIUrl":"10.1016/j.bone.2025.117739","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate the combined effect of the metabolic score for visceral fat (METS-VF) and arterial stiffness on fragility fractures, and to further examine whether arterial stiffness, measured by brachial-ankle pulse wave velocity (baPWV), mediates the association between METS-VF and fragility fractures.</div></div><div><h3>Methods</h3><div>The study included 42,256 participants (mean age, 49.42 ± 13.05 years, 73.36 % male) from the Kailuan cohort, with complete baPWV and METS-VF data, followed until 2022. METS-VF ≥ 6.86 was defined as the high group and &lt; 6.86 as the low group, while baPWV ≥1800 cm/s was defined as the arterial stiffness group and &lt; 1800 cm/s as the normal group. Participants were further classified into four combined groups, with the low METS-VF and normal baPWV group serving as the reference group. Multiplicative and additive interaction analyses were applied, and Cox regression models estimated hazard ratios (HRs) with 95 % confidence intervals (CIs). Mediation analysis assessed the role of baPWV.</div></div><div><h3>Results</h3><div>During a mean follow-up of 7.47 years, 367 participants experienced fragility fractures. A significant additive interaction between METS-VF and baPWV was observed. (Additive: relative excess risk due to the interaction [RERI] = 0.51, 95 % CI 0.04–0.98; Multiplicative, HR = 0.73, 95 % CI 0.69–1.71). After adjusting for covariates, HRs for incident fractures compared to the reference group were 1.39 (95 % CI, 1.02–1.90) for Group 2, 2.21 (95 % CI, 1.60–3.04) for Group 3, and 3.32 (95 % CI, 2.40–4.57) for Group 4. Additionally, baPWV mediated 13.08 % of the association between METS-VF and fracture risk.</div></div><div><h3>Conclusions</h3><div>Higher METS-VF and arterial stiffness levels were associated with an increased risk of fragility fractures, and arterial stiffness, assessed by baPWV, partly mediated this association.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117739"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620922","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":"Hydrogen intervention attenuates chronic hypoxia-induced bone degeneration and multi-organ damage via modulation of the gut microbiota","authors":"Suying Zhu ,&nbsp;Doudou Hao ,&nbsp;Yanli Chen ,&nbsp;Zhiyou Shi ,&nbsp;Yang Zhong ,&nbsp;Fengying Zhang ,&nbsp;Feng Tang ,&nbsp;Suyuan Wang ,&nbsp;Yunhong Wu","doi":"10.1016/j.bone.2025.117718","DOIUrl":"10.1016/j.bone.2025.117718","url":null,"abstract":"<div><div>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., <em>Lactobacillus</em>), 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.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117718"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145508455","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":"Accelerometer-derived daily impact score is positively associated with bone strength accrual during adolescence","authors":"Christina J. Alexander ,&nbsp;Heather M. Macdonald ,&nbsp;Heather A. McKay ,&nbsp;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> &lt; 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":"2026-02-01","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}

{"title":"Transformer-based multi-scale feature fusion for real-time CT bone metastasis detection","authors":"Weiming Xie ,&nbsp;Xiaozhou Bai ,&nbsp;Miao Liu ,&nbsp;Haonan Shangguan ,&nbsp;Ying Zhan ,&nbsp;Xiaodan Wu ,&nbsp;Wei Zhang ,&nbsp;Yusong Pei ,&nbsp;Guoxu Zhang ,&nbsp;Zhiguo Wang ,&nbsp;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":"2026-02-01","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}

{"title":"Enhanced fracture repair in p21−/− mice is mediated through increased callus mineralization","authors":"Alexandra Olsen ,&nbsp;Priyatha Premnath ,&nbsp;Scott Brunet ,&nbsp;Leila Larijani ,&nbsp;Sarah L. Manske ,&nbsp;Leah Ferrie ,&nbsp;Neil A. Duncan ,&nbsp;Derrick E. Rancourt ,&nbsp;Ralph S. Marcucio ,&nbsp;Roman Krawetz","doi":"10.1016/j.bone.2025.117732","DOIUrl":"10.1016/j.bone.2025.117732","url":null,"abstract":"<div><div>Fracture healing is a complex, multi-phase process involving mesenchymal progenitor cell (MPC) recruitment, chondrogenesis, osteogenesis and bone remodelling. The cyclin-dependent kinase inhibitor p21 is known to regulate cell cycle progression and has been implicated in tissue regeneration. Here, we investigated the role of p21 in endochondral fracture repair using a transverse tibial fracture model in physiologically normal mice. Prx1CreERT2-GFP;R26RTdtomato mice on C57BL/6 and <em>p21</em>^−/− backgrounds enabled lineage tracing of MPCs. Longitudinal in vivo micro-CT, histological analysis, tissue cytometry and mechanical testing were used to assess callus formation, cellular composition, and mechanical integrity.</div><div>Our results demonstrate that <em>p21</em>^−/− mice exhibit enhanced bone regeneration, with significantly higher bone mineral density (BMD) and bone volume fraction (BV/TV) in the fracture callus at 2 and 4 weeks post-fracture (wpf). Histology revealed increased <em>Prx1</em>⁺ cell recruitment, along with greater expression of chondrogenic (Sox9) and osteogenic (BSP) markers in <em>p21</em>^−/− mice at 2wpf. Biomechanical testing showed that despite similar strength, <em>p21</em>^−/− calluses had reduced toughness, suggesting altered matrix remodelling.</div><div>Collectively, our findings highlight <em>p21</em> as a negative regulator of bone regeneration, likely through modulation of MPC recruitment and differentiation. Together, these data suggest therapeutic targeting of <em>p21</em> may enhance fracture healing and counteract osteoporosis in terms of bone remodelling and repair.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117732"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145558656","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":"ED-71 alleviates OVX-induced osteoporosis by inhibiting macrophage senescence through SIRT1/PGC-1α pathway: A potential therapeutic approach","authors":"Yaqiu Fu ,&nbsp;Lingxiao Meng ,&nbsp;Minglei Zhang ,&nbsp;Lingshuang Li ,&nbsp;Hongrui Liu ,&nbsp;Wanli Ma ,&nbsp;Minqi Li","doi":"10.1016/j.bone.2025.117737","DOIUrl":"10.1016/j.bone.2025.117737","url":null,"abstract":"<div><div>Postmenopausal osteoporosis (PMOP) is a prevalent condition among postmenopausal women, closely linked to estrogen deficiency, aging, and oxidative stress. Cellular senescence, through mechanisms such as the senescence-associated secretory phenotype (SASP) and bone marrow stromal cells (BMSCs) differentiation imbalance, disrupts bone homeostasis in PMOP. Macrophages play a critical role in maintaining bone homeostasis. However, the extent of macrophage senescence in PMOP and the mechanisms by which it disrupts bone homeostasis have not yet been elucidated. Eldecalcitol (ED-71), a novel drug, has shown potential in osteoporosis treatment, though its effects on macrophage are not fully elucidated. In this study, using hydrogen peroxide (H₂O₂), we induced senescence in macrophages and assessed senescence-associated markers by SA-β-gal staining, Western blotting, and RT-qPCR. We then employed an indirect co-culture system to investigate the paracrine impact of these senescent macrophages on the osteogenic differentiation of BMSCs. The PMOP model was established using ovariectomy (OVX) in mice, followed by histological evaluation. Both 17β-Estradiol (E2) and ED-71 effectively reduced cellular senescence-related indicators such as p16, p53 and β-galactosidase in macrophages, suggesting E2 can alleviate macrophage senescence, and ED-71 may serve as an alternative. Co-culture systems revealed that senescent macrophages impaired BMSCs osteogenic differentiation, an effect reversed by ED-71. SIRT1 inhibition with EX-527 disrupted ED-71's anti-senescence action. Additionally, ED-71 improved bone mass and aging in OVX mice. In conclusion, ED-71 alleviates macrophage senescence via the SIRT1/PGC-1α signaling axis, thereby enhancing BMSC osteogenic potential and mitigating bone loss in OVX-induced osteoporosis.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117737"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145607904","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 comprehensive multi-layered analysis reveals genetic pleiotropy underlying coronary artery calcification and bone mineral density","authors":"Tao Han ,&nbsp;Yang Qu ,&nbsp;Jiangbo Zhu ,&nbsp;Linna Sha ,&nbsp;Bowen Lei ,&nbsp;Rong Xiang ,&nbsp;Xunying Zhao ,&nbsp;Jiaojiao Hou ,&nbsp;Qin Deng ,&nbsp;Sirui Zheng ,&nbsp;Jinyu Zhou ,&nbsp;Ting Yu ,&nbsp;Xin Song ,&nbsp;Bin Yang ,&nbsp;Yangdan Zhong ,&nbsp;Maoyao Xia ,&nbsp;Douglas P. Kiel ,&nbsp;Xia Jiang","doi":"10.1016/j.bone.2025.117719","DOIUrl":"10.1016/j.bone.2025.117719","url":null,"abstract":"<div><h3>Objectives</h3><div>Subclinical atherosclerosis and osteoporosis are often present together in the same individual, but their common mechanisms remain unclear. This study aims to investigate the pleiotropic relationship underlying coronary artery calcification (CAC) and estimated calcaneal bone mineral density (eBMD), providing molecular insights into their observed phenotypic associations.</div></div><div><h3>Methods</h3><div>Genetic correlation between CAC and eBMD was estimated based on genome-wide summary statistics. Shared loci were examined at the levels of single-nucleotide polymorphism (SNP), multi-SNP, and gene expressions to provide insights into genetic pleiotropy. Sensitivity analyses using data of DXA-derived BMD at femoral neck and lumbar spine were performed to validate key findings. Pathway enrichment analyses were conducted on significant shared loci to explore potential biological mechanisms.</div></div><div><h3>Results</h3><div>Despite an absence of a global genetic correlation, partitioning the genome into independent regions revealed five significant signals. Through subsequent multi-layered analysis, we identified 211 non-overlapping significant shared genes, including 190 from single-SNP-level, 27 from multi-SNP-level, and 3 from gene expression level, underscoring the widespread pleiotropy across CAC and eBMD. Notably, the shared signals were predominantly concentrated on chromosome 17, with <em>SMG6</em> and <em>PAFAH1B1</em> highlighted as crucial pleiotropic genes, and both were further confirmed by sensitivity analyses. Pathway enrichment analyses revealed oxidative stress regulation and the ubiquitin-proteasome system as critical biological mechanisms potentially linking the two traits.</div></div><div><h3>Conclusion</h3><div>Our study demonstrates that the observed association between CAC and eBMD is mainly driven by pleiotropic associations.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117719"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145476841","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}