Bone最新文献

{"title":"Pulsed ultrasound and moderate exercise accelerate bone healing in an experimental tibial fracture model: biochemical, radiological and biomechanical evidence","authors":"Ligia Milanez Venturini ,&nbsp;Daniella Pacheco dos Santos Haupenthal ,&nbsp;João Afonso Spillere Dajori ,&nbsp;Laura de Roch Casagrande ,&nbsp;Rubya Pereira Zaccaron ,&nbsp;Camila da Costa ,&nbsp;Igor Ramos Lima ,&nbsp;Fernando Russo Costa do Bomfim ,&nbsp;Sabrina Zanchetta Lanza ,&nbsp;Yaodong Gu ,&nbsp;Anand Thirupathi ,&nbsp;Paulo Cesar Lock Silveira ,&nbsp;Alessandro Haupenthal","doi":"10.1016/j.bone.2025.117498","DOIUrl":"10.1016/j.bone.2025.117498","url":null,"abstract":"<div><div>Currently, therapeutic strategies involving mechanical stress play a key role in fracture consolidation. However, no literary evidence exists regarding the combined effects of low-intensity pulsed ultrasound (LIPUS) and moderate aerobic exercise. This study aimed to investigate the effects of LIPUS and moderate aerobic exercise on bone consolidation in 48 male Wistar rats. The animals were divided into four groups (<em>n</em> = 12 per group): Bone Fracture (BF); BF + LIPUS; BF + Exercise (Ex); BF + Ex + LIPUS. A transverse osteotomy with Kirschner wire fixation was performed, followed by therapeutic interventions for 19 days, three times a week. LIPUS was applied for 10 min (1.5 MHz, 0.4 W/cm², 3 cm² area), and aerobic exercise lasted 30 min/day with progressive speed. Radiographic analyses were conducted on days 1, 12, and 24 post-fracture, and euthanasia occurred 72 h after the final session. The combined group exhibited improved radiographic scores and increased birefringent collagen fibers. IL-4, IL-10, and TGF-β levels were significantly higher in treated groups, particularly the combined intervention. Additionally, oxidative stress markers showed reduced nitrite levels, controlled sulfhydryl oxidation, and enhanced SOD and GSH activity. Biomechanically, the combined group tolerated higher loads and demonstrated superior deformation capacity and tissue elasticity. The combination of aerobic exercise and LIPUS enhanced radiographic healing, modulated inflammation, reduced oxidative stress, and improved mechanical properties, supporting its potential for fracture rehabilitation.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"197 ","pages":"Article 117498"},"PeriodicalIF":3.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882851","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":"Sex-specific association between dietary carbohydrate intake and bone mineral density among American adolescents: National Health and Nutrition Examination Survey","authors":"Chunhong Guo ,&nbsp;Jianmin Qu ,&nbsp;Keyi Li","doi":"10.1016/j.bone.2025.117493","DOIUrl":"10.1016/j.bone.2025.117493","url":null,"abstract":"<div><h3>Background</h3><div>The association between dietary carbohydrate intake and bone mineral density (BMD) remains controversial, and research on this topic among adolescents is lacking. This study aimed to examine the relationship between dietary carbohydrate intake and BMD in adolescents.</div></div><div><h3>Methods</h3><div>This study examined data from adolescents (12–19 years) in the National Health and Nutrition Examination Survey (NHANES) (2005–2010). Dietary carbohydrate intake was assessed via two 24-hour recalls. BMD at the lumbar spine, total spine, total femur, and femoral neck was measured by dual-energy X-ray absorptiometry (DXA). A two-day dietary weighted multivariate regression analysis was employed to adjusted for covariates and assess the relationship between carbohydrate intake and BMD. The consistency of the associations and potential modifying factors were further evaluated through stratification and interaction analyses, both weighted by the two-day dietary data. Additionally, stratified curve fitting elucidated sex-specific differences in this relationship.</div></div><div><h3>Results</h3><div>After excluding missing data, 2616 adolescents aged 12–19 years were included in the study. In the fully adjusted two-day dietary sample weighted analysis model, a positive association was observed between dietary carbohydrate intake and BMD among all participants. Dietary carbohydrate intake was positively associated with lumbar spine BMD (β = 1.31, 95 % CI = 0.38–2.23), total spine BMD (β = 1.31, 95 % CI = 0.39–2.24), and femoral neck BMD (β = 0.91, 95 % CI = 0.05–1.77) among all participants. Subgroup analyses revealed a significant sex interaction effect (<em>P</em> &lt; 0.05). Subsequently, stratified curve fitting and sex-specific multivariate regression analyses were conducted. The results indicated a positive correlation between dietary carbohydrate intake and BMD in males, whereas no such correlation was observed in females. The multivariate analysis results further confirmed the sex-specific differences in the relationship between dietary carbohydrate intake and BMD, consistent with the initial findings.</div></div><div><h3>Conclusion</h3><div>Our study demonstrated that carbohydrate consumption significantly enhances BMD during adolescent bone growth. This effect is sex-specific.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"197 ","pages":"Article 117493"},"PeriodicalIF":3.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882850","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":"Ergothioneine alleviates osteoporosis via the ROS-MAPK signaling Axis","authors":"Zhen Guo ,&nbsp;Yiwen Huang ,&nbsp;Xiaowei Wang ,&nbsp;Yi Han ,&nbsp;Ang Li ,&nbsp;Yiyang Qu ,&nbsp;Lin Chen ,&nbsp;Meihang Du ,&nbsp;Yiming Zhang ,&nbsp;Yuanzhi Xu","doi":"10.1016/j.bone.2025.117496","DOIUrl":"10.1016/j.bone.2025.117496","url":null,"abstract":"<div><div>The accumulation of reactive oxygen species (ROS) within cells regulates the formation and function of osteoclasts, which is crucial therapeutic target for the treatment of osteoporosis. Ergothioneine (EGT) is a rare amino acid with strong antioxidant and anti-inflammatory properties. However, its application on osteoporosis has not been reported. In this study, we investigated the effects of EGT on osteoclastogenesis in vitro and in ovariectomized (OVX) mice. The results revealed that EGT could suppress RANKL-induced podosome belt formation and osteoclast development in vitro, while reducing intracellular ROS levels by upregulating key antioxidant enzymes, including HO-1 and Catalase. EGT was also found to downregulate the expression of critical osteoclast-specific proteins such as Trap, c-Fos, and Ctsk through attenuation of MAPK signaling. The potential of EGT to protect against trabecular bone loss in OVX mice was further demonstrated by micro-CT imaging, possibly by reducing osteoclast numbers shown by histological outcomes. These findings together highlighted the potential value of EGT as a novel tool for treating osteoporosis through its ability to suppress osteoclastogenesis and mitigate the accumulation of intracellular ROS.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"197 ","pages":"Article 117496"},"PeriodicalIF":3.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882849","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":"Small and porous ossicles, with flat stapes footplate and incudal fractures in the oim mouse model of osteogenesis imperfecta","authors":"Maialen Ugarteburu ,&nbsp;Michael Doube ,&nbsp;Lukasz Witek ,&nbsp;Christoph Rau ,&nbsp;Luis Cardoso ,&nbsp;Claus-Peter Richter ,&nbsp;Alessandra Carriero","doi":"10.1016/j.bone.2025.117495","DOIUrl":"10.1016/j.bone.2025.117495","url":null,"abstract":"<div><div>Hearing loss affects approximately 70% of individuals with osteogenesis imperfecta (OI), a genetic connective tissue disorder characterized by bone fragility and deformities. No effective treatments exist for OI hearing loss, and its etiology is unknown limiting the development of new targeted therapies. This work investigates the impact of OI type I collagen mutations on the ossicle bone properties in the homozygous <em>oim</em> mouse model of severe OI, which is known to exhibit hearing loss. The morphology and porosity of the ossicles of 14-week-old <em>oim</em> and wild-type mice were analyzed using high-resolution synchrotron radiation microtomography. Additionally, the collagen fibers structure, bone tissue composition and mechanical properties were evaluated through second harmonic generation microscopy, Raman spectroscopy, and nanoindentation. The results demonstrated that <em>oim</em> ossicles are small, highly porous with an elevated lacunar number density, a flat stapes footplate and a small malleal processus brevis. One-in-two <em>oim</em> ossicles had incudomalleal joint abnormalities, exhibiting either a localized fracture in the incus head or a joint space widening. No differences were observed in collagen fibers structure, bone tissue composition and mechanical properties. These findings suggest that bone fractures observed in the <em>oim</em> incudes may contribute to their reported hearing loss. However, the underlying mechanism for these fractures' development remains to be investigated, as they do not appear to result from changes in bone tissue properties (collagen fibers organization, tissue composition or mechanical properties). Instead, they may be associated with joint space widening, and possibly altered ossicle chain kinematics.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"196 ","pages":"Article 117495"},"PeriodicalIF":3.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882353","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":"Characterization of strains induced by in vivo locomotion and axial tibiotarsal loading in a chukar partridge model","authors":"Murat Horasan ,&nbsp;Kari A. Verner ,&nbsp;Russell P. Main ,&nbsp;Eric A. Nauman","doi":"10.1016/j.bone.2025.117497","DOIUrl":"10.1016/j.bone.2025.117497","url":null,"abstract":"<div><div>Rodent models have offered valuable insights into the mechanobiological mechanisms that regulate bone adaptation responses to dynamic mechanical stimuli. However, using avian models may provide new insights into the mechanisms of bone adaptation to dynamic loads, as bird bones have distinct features that differ from mammalian bones. This paper illuminates these aspects by evaluating the mechanical environment in a novel avian, chukar partridge tibiotarsus (TBT), during fast locomotion and in cortical and cancellous tissue under <em>in vivo</em> dynamic compressive loading within the TBT. We measured <em>in vivo</em> mechanical strains at the TBT midshaft on the anterior, medial, and posterior surfaces during locomotion at various treadmill speeds. The mean <em>in vivo</em> strains measured on the anterior, medial, and posterior surfaces of the TBT midshaft were 154 με, -397 με, and -438 με, respectively, at a treadmill speed of 2 m/s. The mean experimentally measured strains on the anterior, medial, and posterior surfaces of the TBT were 114.7 με, -952.6 με, and -593.7 με under an <em>in vivo</em> dynamic compressive load of 130 N. The study, which employs a micro-computed tomography (microCT) based finite element model in combination with diaphyseal strain gauge measures, found that cancellous strains were greater than those in the midshaft cortical bone. Sensitivity analyses revealed that the material property of cortical bone was the most significant model parameter. In the midshaft cortical volume of interest (VOI), daily dynamic loading increased the maximum moment of inertia and reduced the bone area in the loaded limb compared to the contralateral control limb after three weeks of loading. Despite the strong correlations between the computationally modeled strains and experimentally measured strains at the medial and posterior gauge sites, no correlations existed between the computationally modeled strains and strain gradients, and histologically measured bone formation thickness at the mid-diaphyseal cross-section of the TBT.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"196 ","pages":"Article 117497"},"PeriodicalIF":3.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869403","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":"Oral versus intravenous antibiotics for bone and joint infections: Systematic review and meta-analysis of randomized controlled trials","authors":"João P.C. Lima ,&nbsp;Kauê A. Chagas ,&nbsp;Lucas B.P. Oliveira ,&nbsp;Bruno S.B. Filho ,&nbsp;Flávia M.R. Vital","doi":"10.1016/j.bone.2025.117494","DOIUrl":"10.1016/j.bone.2025.117494","url":null,"abstract":"<div><h3>Background</h3><div>Recent trials suggest oral (PO) antibiotics may be as effective as prolonged intravenous (IV) regimens in specific clinical scenarios. This meta-analysis compared PO and IV antibiotic therapy in bone and joint infections.</div></div><div><h3>Materials and methods</h3><div>PubMed, Embase and CENTRAL databases were searched for published trials from inception until February 2025 for randomized clinical trials (RCTs) that enrolled patients of any age with confirmed bone and/or joint infections compared oral versus intravenous antibiotic therapy and reported at least one of the prespecified outcomes.</div></div><div><h3>Results</h3><div>Nine RCTs (1723 patients) published from 1987 to 2025 were included. PO and IV therapies showed comparable efficacy in treatment failure (RR 0.96; 95 % CI 0.78–1.17; <em>p</em> = 0.68; I² = 0 %) and adverse events (RR 1.00; 95 % CI 0.90–1.12; I² = 10 %; <em>p</em> = 0.94). Overall, recurrence rates were similar. However, a subgroup analysis excluding fracture-related infections favored IV therapy (RR 1.47; 95 % CI 1.08–2.02; I² = 0 %; <em>p</em> = 0.02). Superinfection rates showed no difference (RR 1.12; 95 % CI 0.32–3.98; I² = 0 %; <em>p</em> = 0.86). Although not statistically significant, hospitalization duration may be shorter with PO therapy (MD -5.03 days; 95 % CI -15.84–5.77; I² = 4 %; <em>p</em> = 0.36).</div></div><div><h3>Conclusion</h3><div>Appropriately selected PO antibiotic regimens demonstrate comparable efficacy and safety to IV therapy in bone and joint infections, although there is a slight tendency to increase the recurrence of infections. These findings support a shift toward oral therapy in carefully chosen patients.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"196 ","pages":"Article 117494"},"PeriodicalIF":3.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882352","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":"Reverse engineering Frost's mechanostat model in mouse tibia: Insights from combined PTH and mechanical loading","authors":"Natalia M. Castoldi ,&nbsp;Amine Lagzouli ,&nbsp;Edmund Pickering ,&nbsp;Lee Meakin ,&nbsp;David M.L. Cooper ,&nbsp;Peter Delisser ,&nbsp;Peter Pivonka","doi":"10.1016/j.bone.2025.117491","DOIUrl":"10.1016/j.bone.2025.117491","url":null,"abstract":"<div><div>Osteoporosis is a widespread skeletal disease impacting billions, with treatments aimed at enhancing bone mass or preventing bone loss essential for reducing fracture risk and related health complications. Clinical evidence shows that intermittent parathyroid hormone (PTH) treatment increases cortical width at certain skeletal sites, with effects further amplified when combined with mechanical loading (ML), making this pharmacological and exercise approach promising for dual osteoporosis therapy. However, the mechanisms through which PTH enhances osteogenic response are not fully understood. This study uses <span><math><mi>μ</mi></math></span> CT endpoint imaging data from the mouse tibia loading model together with mechanical assessment of strain patterns in cortical bone to quantitatively compute parameters in Frost's mechanostat model. Particularly, we investigate the effects of PTH alone and in combination with ML on bone formation threshold and rate. Our analysis shows that PTH alone promotes periosteal bone formation independently of strain patterns induced by habitual loading in a dose-dependent manner. PTH lowers the bone formation modeling threshold (<span><math><msub><mi>MES</mi><mi>m</mi></msub></math></span>) in bones undergoing ML in a dose-dependent and site-specific manner. The highest sensitivity is observed around 37 % of tibial height, where <span><math><msub><mi>MES</mi><mi>m</mi></msub></math></span> decreases from <span><math><mn>1060.6</mn><mspace></mspace><mi>μ</mi><mi>ε</mi></math></span> in untreated bones to <span><math><mn>212.1</mn><mspace></mspace><mi>μ</mi><mi>ε</mi></math></span> at an <span><math><mn>80</mn><mspace></mspace><mi>μ</mi></math></span>g/kg/day g PTH dose. This region also exhibits the highest adaptation response, with a maximum modeling velocity (MaxFL) of approximately <span><math><mn>7</mn><mspace></mspace><mi>μ</mi><mi>ε</mi></math></span>/day at <span><math><mn>80</mn><mspace></mspace><mi>μ</mi></math></span>g/kg/day PTH. Although the formation velocity modulus (FVM) increases in PTH-treated bones compared to untreated ones across all regions, this change is not dose-dependent.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"197 ","pages":"Article 117491"},"PeriodicalIF":3.5,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143923272","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 effect of oral colchicine and vitamin K1 on bone metabolism in patients with diabetes mellitus: A post-hoc analysis of a 2 × 2 factorial randomized controlled trial with 18F-sodium fluoride positron emission tomography","authors":"Jamie W. Bellinge ,&nbsp;Marc Sim ,&nbsp;Roslyn J. Francis ,&nbsp;Sing Ching Lee ,&nbsp;Dick C. Chan ,&nbsp;Christian M. Girgis ,&nbsp;Gerald F. Watts ,&nbsp;Joshua R. Lewis ,&nbsp;Carl J. Schultz","doi":"10.1016/j.bone.2025.117492","DOIUrl":"10.1016/j.bone.2025.117492","url":null,"abstract":"<div><h3>Purpose</h3><div>Diabetes mellitus (DM) confers an increased risk of fracture. Fracture risk stratification techniques are imperfect, and preventative therapies are sparse. We aimed to describe features associated with a dysfunctional bone metabolism determined by ¹⁸F-Sodium Fluoride Positron Emission Tomography (¹⁸F-NaF PET) in patients with DM and test the effects of vitamin K1 and colchicine therapy on vertebral ¹⁸F-NaF activity.</div></div><div><h3>Methods</h3><div>This is a post-hoc analysis of a 2 × 2 factorial randomized double-blind placebo-controlled trial. Participants aged 50–80 with DM underwent ¹⁸F-NaF PET/CT imaging at baseline, 3 months of therapy with vitamin K1 (10mg/daily) or placebo, and colchicine (0.5 mg/day) or placebo and repeat ¹⁸F-NaF PET/CT. The ¹⁸F-NaF vertebral mean standardized uptake value (SUVmean) and the CT estimated bone mineral density (BMD) (in Hounsfield units) was evaluated from thoracic vertebra.</div></div><div><h3>Results</h3><div>In total, 149 individuals (66.4 % male, mean age 65.5 ± 6.8 years) were included. Male sex (β −1.421, 95 % CI [−1.826, −1.016], <em>p</em> &lt; 0.001), duration of DM in years (−0.021 [−0.039, −0.002], <em>p</em> = 0.030) and CT estimated vertebral BMD (0.011 [0.006, 0.015], p &lt; 0.001) were independently associated with the SUVmean. The change in the SUVmean was similar between vitamin K1 or placebo groups (−0.07 ± 0.64 v 0.07 ± 0.69, <em>p</em> = 0.20). Participants receiving colchicine therapy had a greater reduction in the SUVmean, compared with placebo (−0.12 ± 0.72 v 0.11 ± 0.60, <em>p</em> = 0.039).</div></div><div><h3>Conclusion</h3><div>¹⁸F-NaF PET may be a useful measure of vertebral bone metabolism in people with DM. Three months of oral colchicine reduced the ¹⁸F-NaF vertebral SUVmean, whereas Vitamin K1 had no effect. The findings should be considered hypothesis generating.</div><div><strong>Trial Registration</strong>: <span><span>www.anzctr.org.au</span><svg><path></path></svg></span> (ACTRN12616000024448).</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"196 ","pages":"Article 117492"},"PeriodicalIF":3.5,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859159","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 2D-registration algorithm for the correction of motion-induced misalignments of consecutive image stacks in multi-stack high-resolution peripheral quantitative CT scans","authors":"M.S.A.M. Bevers ,&nbsp;S. Moharir ,&nbsp;F.L. Heyer ,&nbsp;C.E. Wyers ,&nbsp;J.P. van den Bergh ,&nbsp;B. van Rietbergen","doi":"10.1016/j.bone.2025.117490","DOIUrl":"10.1016/j.bone.2025.117490","url":null,"abstract":"<div><div>Multi-stack imaging using high-resolution peripheral quantitative CT (HR-pQCT) can involve misalignments of consecutive image stacks (‘stack shift’) due to subject movement during scan acquisition. We developed a simple, 2D-registration algorithm for the correction of stack shifts in multi-stack HR-pQCT scans and investigated 1) the differences in standard HR-pQCT parameters and repeatability between before and after stack-shift correction; and 2) the correlation between the transformation needed for the stack-shift correction and corresponding difference in HR-pQCT parameters. The algorithm generates an artificial stack overlap of two slices, then rigidly registers the overlapping region (only in-plane translation allowed), and subsequently applies the resulting translation to the proximal stack. The algorithm was applied to data of 23 men and women with three same-day repeated scans (69 radius and 63 tibia scans, Dataset 1) and of 48 postmenopausal women with 78 radius scans taken at two time points with 12-week interval (Dataset 2). In both datasets, median differences in HR-pQCT parameters between before and after stack-shift correction were mostly significant yet small (≤0.53 %). The differences could vary considerably between subjects and ranged between −12.1 % and +35.8 % for cortical porosity, stiffness, and failure load. For the other HR-pQCT parameters, the differences ranged between ±0.8 % (Dataset 1) and between −4.5 % and +0.9 % (Dataset 2) among subjects. Spearman correlations between the magnitude of the translation and corresponding difference in HR-pQCT parameters were significant for most parameters in both datasets and strongest for stiffness and failure load (ρ = 0.687–0.947; <em>p</em> &lt; 0.01). Based on Dataset 1, coefficients of variation differed between ±0.3 percentage points after stack-shift correction as compared to before. To conclude, correction of stack misalignments in two-stack HR-pQCT scans using our algorithm resulted in significant but negligible median differences in HR-pQCT parameters and precision, but differences could exceed least-significant differences and thereby be clinically relevant in individual subjects. The translation needed for the stack-shift correction correlated significantly with the difference in most HR-pQCT parameters, thereby potentially serving as objective measure for stack-shift severity. The algorithm can be applied directly after scan reconstruction, at low computational cost and without negative effects from image interpolation.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"197 ","pages":"Article 117490"},"PeriodicalIF":3.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886319","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":"Rhizoma Drynariae-derived EV-like particles alleviate osteoporosis by promoting osteogenic differentiation in BMSCs through the activation of the hsa_circ_0001275/miR-422a pathway","authors":"Jiawen Shen ,&nbsp;Yuzhen Chen ,&nbsp;Mingyue Pan ,&nbsp;Sirui Zhou ,&nbsp;Yukun Xu ,&nbsp;Fubin Liu ,&nbsp;Tianxin Qiu ,&nbsp;Dongxiao Li ,&nbsp;Qing Zhao ,&nbsp;Kewei Zhao","doi":"10.1016/j.bone.2025.117489","DOIUrl":"10.1016/j.bone.2025.117489","url":null,"abstract":"<div><h3>Background</h3><div>Osteoporosis (OP) is the most prevailing primary bone disease caused by the imbalance between bone resorption and formation. Rhizoma Drynariae-derived EV-like particles (RD-EVLP) perform the anti-osteoporosis effect by promoting the osteogenic differentiation of human bone marrow mesenchymal stem cells (h-BMSCs) which may be regulated by circular RNAs (circRNAs) and microRNAs (miRNAs). This study aimed to reveal the functional roles and mechanisms of the RD-EVLP regulating osteogenic differentiation of osteoporosis through the activation of hsa_circ_0001275 sponging miR-422a.</div></div><div><h3>Results</h3><div>Notably, RD-EVLP isolated from fresh Rhizoma Drynariae <em>via</em> differential ultracentrifugation demonstrated three critical pharmacological attributes: (1) excellent biosafety profile with non-toxic and gastrointestinal stability, (2) bone-targeting specificity evidenced by femoral accumulation, and (3) potent anti-osteoporotic effects through promoting osteogenic differentiation <em>in vivo</em>. Meanwhile, RD-EVLP effectively internalized by h-BMSCs, enhanced proliferation of h-BMSCs, and promoted osteogenic differentiation and bone formation <em>in vitro</em>. For another, hsa_circ_0001275 and insulin like growth factor 1 receptor (IGF1R) expressions were upregulated while miR-422a expression was downregulated during osteogenic differentiation. Knockdown of hsa_circ_0001275 inhibited mineralized nodule formation. Moreover, miR-422a was a target of hsa_circ_0001275 and knockdown of miR-422a promoted mineralized nodule formation and greatly reinforced the expression of runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2), osteocalcin (OCN). What's more, miR-422a suppressed h-BMSCs osteogenic differentiation by downregulating IGF1R. Finally, RD-EVLP promoted osteogenic differentiation by enhancing hsa_circ_0001275 and IGF1R while reducing miR-422a expression levels of h-BMSCs during osteogenic induction.</div></div><div><h3>Conclusion</h3><div>hsa_circ_0001275 could promote osteogenic differentiation by sponging miR-422a to upregulate IGF1R expression and RD-EVLP performed anti-OP activity through hsa_circ_0001275/miR-422a pathway.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"196 ","pages":"Article 117489"},"PeriodicalIF":3.5,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848125","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}