Bone最新文献

{"title":"Engineering composites inspired cortical-trabecular interlocking effect underlies bone strength in mouse vertebrae.","authors":"Rui Mao, Qiao Li, Jie Yao, Chunli Song, Lizhen Wang, Yubo Fan","doi":"10.1016/j.bone.2026.118141","DOIUrl":"https://doi.org/10.1016/j.bone.2026.118141","url":null,"abstract":"<p><p>Bone strength is a major determinant of osteoporotic fracture risk. Current clinical assessments, however, rely primarily on imaging-based surrogates such as bone mineral density, offering limited insight into the integrated mechanical behavior of vertebral bone. Inspired by engineered composite structures, in which interfacial interactions substantially enhance mechanical properties, this study introduces the concept of the cortical-trabecular interlocking effect to characterize the mechanical integration between these two compartments and investigate its contribution to vertebral bone strength. Micro-finite element models of mouse L4 vertebrae (control, mild, and severe osteoporosis) and idealized vertebral models were employed to quantify the independent contributions of isolated cortical bone, isolated trabecular bone, and the cortical-trabecular interlocking effect to whole-bone mechanical properties under axial load. To better characterize the cortical-trabecular interlocking effect, we propose a novel microstructural parameter, Lr.BV/TV, defined as the bone volume fraction within the interlocking ring, an interface region where cortical and trabecular bone are structurally integrated. The cortical-trabecular interlocking effect contributed 12.2-26.1% (mean 19.5%) to vertebral yield strength and its magnitude varied systematically with osteoporosis severity. Notably, asynchronous deterioration of cortical and trabecular bone in osteoporosis constrained the effective utilization of the interlocking effect, whereas well-matched components maximized this effect. Lr.BV/TV was identified as the dominant predictor of vertebral strength and outperformed both cortical thickness and trabecular bone volume fraction, accounting for 45.83% of the total explained variance, with its predictive relevance varying across stages of osteoporosis. These findings advance our understanding of vertebral fragility.</p>","PeriodicalId":93913,"journal":{"name":"Bone","volume":" ","pages":"118141"},"PeriodicalIF":3.6,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Movement regimens drive region-specific humeral adaptation: whole-bone insights from an experimental animal model.","authors":"Sarah Bergren, Tea Jashashvili, Mark Dowdeswell, Kristian J Carlson","doi":"10.1016/j.bone.2026.118139","DOIUrl":"https://doi.org/10.1016/j.bone.2026.118139","url":null,"abstract":"<p><p>Repetitive movements impose distinct loading regimens on long bones, potentially eliciting predictable osteogenic responses and morphological change. Cortical responses to such movements are seldom investigated along whole diaphyses as opposed to selected locations. Morphometric mapping is a technique that is well-suited for comprehensively examining whole diaphyses. To assess responses to different movement regimens, we evaluated humeri of thirty-five female C57BL/6J mice raised from weeks 4 to 20 post-birth in one of three scenarios: linear-dominated (n = 12), turning-dominated (n = 12), and open cage (n = 11) movements. We measured aspects of humeral structure such as diaphyseal cortical thicknesses (Ct.Th), second moments of area (SMA), and deltoid crest angles (DCA) on 3D models and 2D images of humeri generated from high-resolution (microCT) image data. Turning and open-cage individuals exhibited slightly greater Ct.Th than linear individuals in proximal shaft regions. Turning individuals were distinctive in mediolateral reinforcement (SMAs) in distal shaft regions. Individuals in the open cage group tended to exhibit overall greater SMAs than individuals in the other groups. Bayesian probabilities support mean DCA differences between the linear (25.0°) versus the open cage (20.9°) and turning (22.0°) groups. Ultimately, three different movement regimens elicited unique combinations of site- and direction-specific shaft reinforcements and muscle attachment orientations without any substantial differences in overall humeral bone mass. The generally overall greater SMAs of the open cage group suggest benefits to skeletal health (e.g., diversified shaft reinforcement) may be accrued in a non-pharmacological intervention strategy that would emphasize multidirectional rather than repetitive activities.</p>","PeriodicalId":93913,"journal":{"name":"Bone","volume":" ","pages":"118139"},"PeriodicalIF":3.6,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inactivation of the polycomb repressive complex 2 (PRC2) in osteoblasts increases post-natal trabecular bone mass and mechanical bone strength.","authors":"Amel Dudakovic, Sofia Jerez, Christopher R Paradise, M Lizeth Galvan, Eva Kubrova, Oksana Pichurin, Padmini J Deosthale, Gary S Stein, Roman Thaler, Lilian I Plotkin, Andre J van Wijnen","doi":"10.1016/j.bone.2026.118140","DOIUrl":"https://doi.org/10.1016/j.bone.2026.118140","url":null,"abstract":"<p><p>The epigenetic methyltransferases Ezh1 or Ezh2 each interact with two structural proteins (Eed and Suz12) to form Polycomb Repressive Complex 2 (PRC2). Inhibition of Ezh2 stimulates osteoblast differentiation and bone formation, but Ezh2 conditional knockout (cKO) mice have variable skeletal phenotypes. Ezh1 null mice are phenotypically normal. Here, we show that combined homozygous ablation of both Ezh1 and Ezh2 alleles results in a pronounced bone phenotype, suggesting genetic redundancy between Ezh1 and Ezh2. Transient loss of Eed, Suz12 or Ezh2 by siRNA depletion or treatment with distinct PRC2 inhibitors (A395, EED226 and GSK126) enhances differentiation of MC3T3-E1 pre-osteoblasts (i.e., increased Bglap, Ibsp and mineralization). We compared Ezh2 cKO mice with Ezh1 null (KO) mice, and mice with both Ezh2 cKO and Ezh1 KO alleles (dKO mice) in the presence of the Osterix/Sp7-Cre recombination driver. During active bone development (post-natal 8 weeks), both male and female dKO mice exhibit significantly increased L5 trabecular bone mass, femoral cortical thickness and the relative midshaft bone volume (μCT), as well as bone strength (3-point bending) compared to Ezh1 KO or Ezh2 cKO mice. Suppression of Cre recombination using doxycycline (DOX) for 8 weeks prevents the dKO phenotype, but subsequent DOX removal increases trabecular bone mass in dKO mice by 14 weeks. Conditional Eed ablation (which inactivates PRC2/Ezh1 and PRC2/Ezh2) results in a similar high- bone and increased mechanical strength phenotype in male and female Eed cKO. Our findings identify PRC2 as a suppressor of post-natal bone accrual in Osx/Sp7 lineage cells, and a potential target for strategies to improve bone mass accrual.</p>","PeriodicalId":93913,"journal":{"name":"Bone","volume":" ","pages":"118140"},"PeriodicalIF":3.6,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preliminary study on early microvascular ingrowth into distracted callus during distraction osteogenesis-A non-invasive approach to explore the early growth patterns and possible mechanism of distraction osteogenesis in vivo.","authors":"Juan Li, Yonghong Zhang, Yutao Zhang, Dong Wang, Wei Luo, Xiaojin Gao, Yanping Wang, Ruhao Zhang, Yan Li, Ze Zhang, Xinghua Wang, Yanzi Qiao, Weiwei Wu, Bojuan Wang, Hongjie Zhou, Chaoqi Wang, Zemin Liu, Wei Han, Yanming Zhi, Jia Li, Sihe Qin","doi":"10.1016/j.bone.2026.118138","DOIUrl":"10.1016/j.bone.2026.118138","url":null,"abstract":"<p><strong>Background: </strong>Distraction osteogenesis (DO) is critical for repairing large segmental bone defects. Early callus vascularization is essential for bone regeneration; however, real-time microcirculatory assessment remains lacking. This study aimed to elucidate spatiotemporal microvascular network construction in distracted callus using super-resolution contrast-enhanced ultrasound (SR CEUS) and high-frame-rate contrast-enhanced ultrasound (HiFR CEUS) in a sheep tibial DO model.</p><p><strong>Methods: </strong>Six sheep underwent tibial DO. On day 7 of distraction, B-mode ultrasound, \"Firefly\" imaging, SR CEUS, and HiFR CEUS were performed. Quantitative parameters including vessel density (VD), perfusion index (PI), mean intensity, and peak intensity (PKI) were compared among three regions: central high-perfusion area (CHPA), annular low-perfusion area (ALPA), and peripheral high-perfusion area (PHPA).</p><p><strong>Results: </strong>B-mode ultrasound revealed outward bulging of distracted callus. \"Firefly\" imaging detected microcalcifications. SR CEUS showed PHPA (67.58% of cross-sectional area) received centripetal blood flow from periosteum and surrounding soft tissues; CHPA (10.39%) received centrifugal flow from the medullary cavity; ALPA (22.03%), located between them, exhibited significantly lower mean intensity than CHPA/PHPA and significantly lower VD and PI than PHPA (P < 0.05). HiFR CEUS showed perfusion appeared first in CHPA, then PHPA, and lastly ALPA.</p><p><strong>Conclusion: </strong>SR and HiFR CEUS enable non-invasive, dynamic visualization and quantification of microvascular growth in distracted callus, revealing a \"target ring sign\", \"bidirectional fusion\" perfusion pattern, and \"central-first, peripheral-second\" perfusion sequence. ALPA was identified as a hypovascular zone potentially associated with delayed mineralization or cyst formation. This system provides a novel imaging framework for early assessment of callus viability, prediction of osteogenic risk, and guidance of individualized distraction strategies.</p>","PeriodicalId":93913,"journal":{"name":"Bone","volume":" ","pages":"118138"},"PeriodicalIF":3.6,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical phenotype and bone microarchitecture of cutaneous-skeletal hypophosphatemia syndrome: experience from a single center in China.","authors":"Shuquan Zhang, Zhixiang Wang, Ruotong Zhou, Zhe Shi, Yushuo Wu, Qianqian Pang, Ruizhi Jiajue, Lijia Cui, Wei Liu, Yan Jiang, Ou Wang, Mei Li, Xiaoping Xing, Weibo Xia, Yue Chi","doi":"10.1016/j.bone.2026.118137","DOIUrl":"https://doi.org/10.1016/j.bone.2026.118137","url":null,"abstract":"<p><strong>Context: </strong>Cutaneous-skeletal hypophosphatemia syndrome (CSHS) is a rare mosaic RASopathy characterized by epidermal or melanocytic nevi, skeletal dysplasia, and fibroblast growth factor 23 (FGF23)-mediated hypophosphatemic rickets. However, its bone microarchitectural features remain underdefined.</p><p><strong>Objectives: </strong>The study aimed to characterize the clinical, genetic, and skeletal microarchitectural features of CSHS.</p><p><strong>Methods: </strong>We summarized clinical findings of 6 CSHS patients with genetically confirmed somatic RAS mutations. Skeletal involvement was assessed by whole-body bone scintigraphy. High-resolution peripheral quantitative computed tomography parameters at the distal radius and tibia were compared with age- and sex-matched XLH controls (1:3). Literature review of 24 genetically confirmed CSHS patients was performed to assess genotype-phenotype correlation.</p><p><strong>Results: </strong>All patients were confirmed to carry somatic HRAS or NRAS mutation in affected skin. Hypophosphatemia, elevated alkaline phosphatase and elevated FGF23 were found in all patients. Genotype-phenotype correlation analysis did not identify any significant biochemical or systemic burden differences across 3 genotypes. Compared with XLH controls, CSHS patients exhibited significantly reduced total and trabecular volumetric BMD (vBMD), with relatively preserved cortical vBMD. Bone cross-sectional geometry was less expanded than in XLH at the tibia. In addition, thinner trabeculae with greater separation were found at the radius, and the distal tibia showed thinner cortices and decreased cortical porosity. Estimated bone stiffness and failure load were significantly lower at both the radius and tibia.</p><p><strong>Conclusions: </strong>CSHS is associated with pronounced trabecular vBMD impairment and reduced bone strength compared with XLH controls. These findings are consistent with a combined contribution of intrinsic skeletal dysplasia and chronic hypophosphatemia on bone, although further studies are needed to elucidate these mechanisms.</p>","PeriodicalId":93913,"journal":{"name":"Bone","volume":" ","pages":"118137"},"PeriodicalIF":3.6,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wnt10b is required for the increase in cancellous bone caused by oxidized phospholipids blockade.","authors":"Michela Palmieri, Intawat Nookaew, Jeff D Thostenson, Teenamol Joseph, Cecile Bustamante-Gomez, Jesus Delgado-Calle, Joseph J Goellner, Charles A O'Brien, Maria Almeida, Elena Ambrogini","doi":"10.1016/j.bone.2026.118132","DOIUrl":"10.1016/j.bone.2026.118132","url":null,"abstract":"<p><p>Oxidized phospholipids containing phosphatidylcholine (PC-OxPLs), present on oxidized low-density lipoproteins (OxLDL) and apoptotic cells, are pathogenic in osteoporosis. PC-OxPLs are bound by the IgM E06 antibody, which blocks their deleterious effects. Overexpression of the antigen-binding domain of E06 (E06-scFv) increases bone mass in 6-month-old mice and attenuates high fat diet- and age-induced bone loss by increasing osteoblast number and function. The mechanisms mediating the anabolic effect of oxidized phospholipids blockade are unclear. In previous work, we showed that E06-scFv upregulates the expression of Wnt10b and Wnt signaling in vivo. We report herein that the bulk of Wnt10b in the bone microenvironment originates from osteoblast lineage cells. OxLDL decreases the expression of Wnt10b and Wnt target genes in osteoblastic cells, and single cell RNA-sequencing (scRNA-seq) of mesenchymal cells reveals an increase in Wnt10b and Wnt target genes in pre-osteoblasts and osteoblasts of E06-scFv transgenic mice compared to WT. Loss of Wnt10b prevents the increases in BMD by DXA and in vertebral and femoral cancellous bone in 6-month-old E06-scFv transgenic male mice, and attenuates these increases in female mice. Collectively, these findings indicate that oxidized phospholipids decrease bone mass, at least in part, by suppressing Wnt10b.</p>","PeriodicalId":93913,"journal":{"name":"Bone","volume":" ","pages":"118132"},"PeriodicalIF":3.6,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic spectrum and genotype-phenotype associations in Paget's disease of bone: A nationwide multicenter study from Türkiye.","authors":"Dilek Gogas Yavuz, Hazal Salva, Pinar Ata, Ebru Arslan, Onur Hanoglu, Mahsan Azimi, Zeliha Hekimsoy, Hakan Dogruel, Ramazan Sarı, Feyza Yener Ozturk, Yuksel Altuntas, Ilgin Yildirim Simsir, Senem Boz Aksoy, Levent Ozsari, Ayse Kubat Uzum, Nurdan Gul, Ozlem Soyluk Selcukbiricik, Cevdet Duran, Kagan Gungor, Seda Karsli, Meral Mert, Ozlem Turhan Iyidir, Ozge Ozer, Aysen Akalin, Ersen Karakilic, Emre Saygili, Hatice Oner, Anna Abbasgholizadeh, Mustafa Eroglu","doi":"10.1016/j.bone.2026.118134","DOIUrl":"https://doi.org/10.1016/j.bone.2026.118134","url":null,"abstract":"<p><strong>Background: </strong>Paget's disease of bone (PDB) is most prevalent in populations of North-western European ancestry and relatively rare in Middle-Eastern and Asian populations, where the genetic architecture and clinical phenotype are poorly characterized. The aim of this study was to determine, in patients diagnosed with PDB in Turkey, the frequency of SQSTM1 and other associated gene variants, the genotype-phenotype relationship and treatment response, in a multicenter, nationwide setting.</p><p><strong>Methods: </strong>We studied 105 patients with PDB and 96 controls. Genomic DNA from peripheral blood was sequenced in a tiered fashion: SQSTM1 sequencing first, followed by a targeted next-generation sequencing (NGS) panel (including TNFRSF11A, TNFRSF11B, VCP, PFN1, OPTN, COL1A1/2, SP7, CSF1) in SQSTM1-negative cases, on an Illumina MiSeq platform with Sophia DDM analysis and Sanger confirmation. Clinical, biochemical, radiological, bone-mineral-density and treatment data were collected. Patients carrying pathogenic SQSTM1 variants were compared with pathogenic variant-negative patients.</p><p><strong>Results: </strong>Mean age was 67.3 ± 10.4 years (52% women); 68% were symptomatic and 50% had polyostotic disease. Pathogenic SQSTM1 variants were identified in 10/105 patients (9.5%); no control carried an SQSTM1 variant. Panel sequencing in SQSTM1-negative cases additionally identified rare variants of uncertain significance in VCP, TNFRSF11A and TNFRSF11B, and an incidental LRP5 variant (high bone mass/osteosclerosis); these were reported descriptively rather than aggregated into a single frequency. TNFRSF11B c.1086_1127del change was absent from the published PDB literature and might be novel. SQSTM1-positive patients had significantly more extensive disease (polyostotic involvement 90% vs 45%, p = 0.008) and more frequent familial disease (30% vs 5%, p = 0.023), with higher bone-specific alkaline phosphatase (median 206 vs 58 U/L, p = 0.019) and a trend to higher total ALP (355 vs 194 U/L, p = 0.074). Cranial involvement, hearing loss, fracture and deformity did not differ significantly. Ninety-seven percent received bisphosphonates (predominantly zoledronic acid); biochemical remission occurred in 95% and relapse in 34%, without significant difference by genotype.</p><p><strong>Conclusions: </strong>In this Turkish multicenter cohort, pathogenic SQSTM1 variants were associated with more extensive and more frequently familial PDB but not with a poorer response to bisphosphonate therapy. These data extend the genotype-phenotype map of PDB to an understudied population and identify a candidate novel TNFRSF11B variant that require further validation.</p>","PeriodicalId":93913,"journal":{"name":"Bone","volume":" ","pages":"118134"},"PeriodicalIF":3.6,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photobiomodulation therapy versus sham for tibial and metatarsal bone stress injuries in military trainees: A randomized controlled trial.","authors":"Daniel I Rhon, Nathan A Parsons, Tina A Greenlee, Elizabeth Metzger, Steven R Hole, Nelson Hager","doi":"10.1016/j.bone.2026.118135","DOIUrl":"https://doi.org/10.1016/j.bone.2026.118135","url":null,"abstract":"<p><strong>Purpose: </strong>To compare the effectiveness of active versus sham photobiomodulation therapy (PBMT) on time to graduation and bone healing in military trainees with lower extremity bone-stress injuries (BSI).</p><p><strong>Materials and methods: </strong>Participants were trainees at the Medical Education and Training Campus, San Antonio, Texas, with MRI-confirmed metatarsal and/or tibial BSI, enrolled between June 2023 and November 2024. All participants received standard-of-care treatment and were randomized to active or sham PBMT. The primary outcome was time to graduation (days), analyzed with a cause-specific Cox model. Secondary outcomes, assessed at four months, were on-time graduation (yes/no), the Defense and Veterans Pain Rating Scale (DVPRS), the Lower Extremity Functional Scale (LEFS), and bone healing on MRI.</p><p><strong>Results: </strong>103 participants were randomized; 97 included in the final analysis. The mean age (SD) was 23.7 (4.2) years, 52.6% female. Both extremities were affected in 47.4% of the cohort; the tibia in 70.1% and a metatarsal in 28.9% (1.0% both), with BSI severity ranging from Fredericson grade I to IVb. Only 37.1% of participants graduated on time. Time to graduation did not differ between treatment groups (Hazard Ratio for Sham versus Treatment 0.95; 95%CI 0.61 to 1.48; p = 0.83) nor did on-time graduation (Risk Ratio 0.91; 95%CI 0.54 to 1.52; p = 0.71) or BSI healing on MRI (Risk Ratio 0.89; 95%CI 0.68 to 1.16; p = 0.54). Furthermore, sex, laterality, and BSI location did not predict successful on-time graduation. Pain (mean difference [95%CI] -0.74 [-2.31 to 0.83]; p = 0.84) and function (5.95 [-7.92 to 19.81]; p = 0.89) were not significantly different at 4 months.</p><p><strong>Conclusion: </strong>Time to graduation, bone healing, pain intensity, and physical function did not differ significantly between trainees with BSI who received PBMT versus sham. Given the substantial resource investment, these results should be weighed when considering routine use of PBMT to manage BSIs in this setting.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov # NCT05843864.</p>","PeriodicalId":93913,"journal":{"name":"Bone","volume":" ","pages":"118135"},"PeriodicalIF":3.6,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered tissue-to-fibril strain transfer in cortical bone from juvenile female Klotho-deficient mice.","authors":"Kaiyuan Xue, Fanshuo Wang, Li Xi, Himadri Gupta, Nick Terrill, Ying Li","doi":"10.1016/j.bone.2026.118133","DOIUrl":"10.1016/j.bone.2026.118133","url":null,"abstract":"<p><p>Juvenile female Klotho-deficient mice have severe cortical abnormalities, but how the remaining bone matrix partitions deformation across length scales is unclear. We combined in situ tensile testing with synchrotron small-angle X-ray diffraction to quantify tissue and mineralized-collagen-fibril deformation in femoral cortical bone from 5-week-old female wild-type, heterozygous, and homozygous Klotho-deficient mice (n = 5 per group). Quantitative backscattered electron imaging (qBEI) assessed tibial cortical thickness, mineralization and the dark-area fraction of the same sections; phase-contrast microtomography of femur provided qualitative structural context. Effective fibril modulus was higher in heterozygous (14.6 ± 3.5 GPa, p = 0.012) and homozygous mice (13.4 ± 5.5 GPa, p = 0.010) than in wild-type mice (4.3 ± 0.8 GPa). The fibril-to-tissue strain ratio was lower in both Klotho-deficient groups (p = 0.018 and p = 0.028), whereas fibril-orientation dispersion did not differ (p = 0.823). Tissue modulus, failure strain, and failure stress showed no statistically significant genotype differences. Tibial cortices were thinner in both Klotho-deficient groups; the dark-area fraction was higher in homozygous mice (p < 0.001), and mean calcium content was lower in homozygous than wild-type mice (p = 0.011). Mineralization heterogeneity did not differ (p = 0.811). These exploratory findings are consistent with altered tissue-to-fibril strain partitioning associated with Klotho deficiency, together with marked cortical structural deficits, but do not establish the molecular origin of the response. The local X-ray dose was estimated at approximately 0.6 kGy per measurement location, well below the absorbed dose at which X-ray irradiation alters the deformation behaviour of cortical bone. Only female mice at a single juvenile age were studied, so the findings cannot be extrapolated to males or to older animals.</p>","PeriodicalId":93913,"journal":{"name":"Bone","volume":" ","pages":"118133"},"PeriodicalIF":3.6,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-specific zebrafish models reveal a complex phenotypic spectrum in NBAS-associated atypical osteogenesis imperfecta.","authors":"Daniel A Baird, Sookyung Seo, Zuzanna Matelowska, Karthick Navin Mohandass, Alagumeenal Subramanian Annamalai, Aynour Abouelkhair, Myar Zafar, Nurhaziqah Supari, Sarah Baxendale, Catherine A Loynes, Freek van Eeden, Meena Balasubramanian","doi":"10.1016/j.bone.2026.118129","DOIUrl":"https://doi.org/10.1016/j.bone.2026.118129","url":null,"abstract":"<p><p>Neuroblastoma amplified sequence gene (NBAS) variants are associated with short stature, optic atrophy, and Pelger-Huët anomaly (SOPH) syndrome. We previously identified compound heterozygous variants in NBAS to cause atypical Osteogenesis Imperfecta (OI), with these patients presenting with short stature, developmental delay, and recurrent long-bone fractures. However, skeletal disease progression due to these variants and the disease mechanisms underlying NBAS-associated OI remain poorly understood. Here, we provide a clinical update on previously identified patients and investigate the role of NBAS during skeletal development using zebrafish knockout and patient-specific missense variant zebrafish models. Homozygous knockout larvae exhibited delayed operculum development, reduced bone ossification, and defects in Meckel's cartilage morphology and its underlying cellular structure. Homozygous missense larvae displayed milder cartilage defects without any major defects to early skeletal structures. Seemingly opposing phenotypes were observed in compound heterozygous zebrafish carrying the knockout and missense alleles in trans, with no obvious phenotypes seen in the Meckel's cartilage and accelerated operculum development observed. Together, our results demonstrate that different nbas variants differentially affect skeletal development, suggesting complex spectrums of phenotypic and pathogenic mechanisms in NBAS-associated atypical OI.</p>","PeriodicalId":93913,"journal":{"name":"Bone","volume":" ","pages":"118129"},"PeriodicalIF":3.6,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}