Bone最新文献

{"title":"Multiexon COL1A2 deletion as a rare mechanism in osteogenesis imperfecta: Case report and literature review","authors":"Daniela Oliveira ,&nbsp;Pedro M. Almeida ,&nbsp;Sofia Franco ,&nbsp;Raquel Pina ,&nbsp;Rita Cerqueira ,&nbsp;Silvia Modamio-Hoybjor ,&nbsp;Karen E. Heath ,&nbsp;Sérgio B. Sousa ,&nbsp;Fabiana Ramos","doi":"10.1016/j.bone.2026.117810","DOIUrl":"10.1016/j.bone.2026.117810","url":null,"abstract":"<div><h3>Background</h3><div>Osteogenesis imperfecta (OI) is mostly caused by pathogenic variants in <em>COL1A1/COL1A2</em>; while single nucleotide variants predominate, multiexon copy number variants (CNVs) remain under-recognised contributors with incompletely defined phenotypic impacts.</div></div><div><h3>Methods</h3><div>We investigated a fetus presenting severe skeletal dysplasia using NGS with CNV calling and MLPA, clinical and radiologic assessments, and transcript analysis of maternal fibroblasts. We also reviewed the literature and curated databases for reported multiexon <em>COL1A2</em> deletions.</div></div><div><h3>Results</h3><div>The fetus exhibited lethal OI type II features, including progressive long bone shortening and bowing, multiple fractures, diffuse hypomineralisation, and a bell-shaped thorax. Genetic analysis revealed a heterozygous in-frame <em>COL1A2</em> exons 4–17 deletion. Maternal testing identified low-level mosaicism for this large deletion alongside a germline in-frame deletion of exons 12–17. Detailed breakpoint analysis of the exon 12–17 deletion revealed a complex rearrangement characterised by the insertion of an inverted duplicated segment of exon 3 and intron 3 at the deletion junction. Despite these findings, the mother showed only joint hypermobility and a family history of osteoporosis, without overt features of OI.</div></div><div><h3>Conclusions</h3><div>N-terminal in-frame <em>COL1A2</em> deletions show variable expressivity, including perinatal lethality. We report a novel, complex and likely unstable genomic rearrangement which probably predisposed to a secondary, larger deletion. Integrated CNV analysis and parental studies are crucial to ensure accurate recurrence risk counselling.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"206 ","pages":"Article 117810"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095236","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":"Bone mineral density in rheumatoid arthritis patients on antirheumatic therapies: a systematic review","authors":"Owen Taylor-Williams ,&nbsp;Ross Godwin ,&nbsp;Reece Carvallio ,&nbsp;Michaela Taylor-Williams ,&nbsp;Christine Barrett ,&nbsp;Charles Inderjeeth","doi":"10.1016/j.bone.2026.117812","DOIUrl":"10.1016/j.bone.2026.117812","url":null,"abstract":"<div><div>Rheumatoid Arthritis (RA) is associated with increased fracture risk due to systemic bone loss. Whilst new disease modifying antirheumatic drugs (DMARD) have improved disease control, their impacts on bone mineral density (BMD) remains controversial. This systematic review investigates the effects of conventional synthetic (cs), biologic (b), and targeted synthetic (ts) DMARDs on BMD in RA patients. 13,340 records were screened, with 46 studies meeting the inclusion and exclusion criteria, published on PROSPERO (CRD42024534452). Included studies were analysed by their use of specific DMARD, glucocorticosteroids (GCS), antiosteoporotic therapy (AOT) and disease activity. csDMARD appear beneficial to BMD, and on the balance of evidence bDMARD and tsDMARD appear to have a greater effect on BMD. Encouragingly, early data suggests some csDMARD, bDMARD, tsDMARD may be superior to others, however, further research is required to confirm this. Future researchers should consider DMARD mechanism of action on BMD and examine the role of specific csDMARD, bDMARD, and tsDMARD in large cohort studies and trials.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"206 ","pages":"Article 117812"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146095156","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":"Dual inhibition of sclerostin and Notum induces synergistic osteoanabolic action in mice","authors":"Roy B. Choi ,&nbsp;April M. Hoggatt ,&nbsp;Daniel J. Horan ,&nbsp;Connor J. Cunningham ,&nbsp;Robert Brommage ,&nbsp;David R. Powell ,&nbsp;Alexander G. Robling","doi":"10.1016/j.bone.2026.117816","DOIUrl":"10.1016/j.bone.2026.117816","url":null,"abstract":"<div><div>Expanding the number of clinically approved choices for osteoanabolic therapy represents the next hurdle on the osteoporosis treatment horizon. The WNT pathway is involved in stimulating new bone formation, and the most recent FDA-approved anabolic therapy—sclerostin neutralizing antibody—works by stimulating the WNT pathway in bone. The challenge with all current osteoanabolic therapies is the short treatment window in which they are efficacious. One strategy to dealing with this limited anabolic window is to further maximize bone formation during the window, using combination therapy. For example, simultaneous pharmacological or genetic inhibition of the WNT antagonists sclerostin and DKK1 potentiate the already strong effects of sclerostin inhibition alone, particularly in cancellous bone. Considerable interest has emerged regarding other candidates that might be co-inhibited along with sclerostin to potentiate its effects in bone, with specific action on cortical bone. In this communication, partnering sclerostin inhibition with the inhibition of another secreted WNT antagonist, NOTUM, is explored. NOTUM is a secreted WNT deacylase that inactivates WNT ligands and has preferential effects on cortical bone. To evaluate combination therapy involving sclerostin/NOTUM inhibition, double knockout mice for <em>Sost</em> and <em>Notum</em> (<em>Sost</em>^−/−;<em>Notum</em>^−/−) were generated and compared to single knockouts and WT controls. Further experiments were conducted using pharmacologic inhibitors, rather than genomic mutations, for sclerostin (sclerostin neutralizing antibody) and a small molecule inhibitor of NOTUM (LP-922056). Each experiment included evaluation by DXA-derived radiography, μCT, biomechanical testing and bone dynamic histomorphometry. Deletion of <em>Notum</em> alone had mild cortical effects but co-deletion of <em>Sost</em> and <em>Notum</em> improved cortical and some cancellous parameters significantly beyond <em>Sost</em>^−/− mice. Co-inhibition of the protein products with antibody/small molecule were less synergistic, with only a small cortical effect, particularly in younger mice. Taken together, the results suggest the potential to improve efficacy of sclerostin inhibition using NOTUM inhibition is promising, but development of additional NOTUM inhibiting tools and optimization of current tools might be necessary to strengthen the partnership.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"206 ","pages":"Article 117816"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116386","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":"Quantitative assessment of the alignment between human trabecular microstructural orientation and mechanical anisotropy: Implications for Wolff's Law","authors":"Pengwei Xiao","doi":"10.1016/j.bone.2026.117817","DOIUrl":"10.1016/j.bone.2026.117817","url":null,"abstract":"<div><div>Trabecular bone exhibits a highly organized microarchitecture that adapts to its mechanical loading environment, a concept fundamentally described by Wolff's law. However, direct quantitative evidence linking the trabecular microstructural orientation with mechanical anisotropy remains limited. In this study, we quantitatively assessed the alignment between trabecular microstructural orientation and the apparent stiffness tensor using a micro-CT-based finite element (μFE) framework. Fabric tensors and the orientations of individual trabecular plates and rods were derived using the Mean Intercept Length (MIL) method and Individual Trabecula segmentation (ITS) analysis, respectively. The apparent stiffness tensors were obtained through μFE models subjected to three uniaxial compression and three pure shear loading cases. The results demonstrated a strong alignment between the fabric tensor and the apparent stiffness tensor, with an overall alignment index (<span><math><mover><mi>λ</mi><mo>¯</mo></mover></math></span>) of 0.92 (IQR: 0.09). Trabecular plates exhibited a high degree of alignment with the apparent stiffness tensor (<span><math><mover><mi>λ</mi><mo>¯</mo></mover></math></span>: 0.88, IQR: 0.15), whereas trabecular rods demonstrated a substantially lower degree of alignment (<span><math><mover><mi>λ</mi><mo>¯</mo></mover></math></span>: 0.36, IQR: 0.19). Moreover, the alignment between the principal axis of trabecular plates and the apparent stiffness tensor increased with the degree of anisotropy (DA), while the alignment of trabecular rods decreased with increasing DA. These findings provide quantitative evidence supporting Wolff's law, confirming that trabecular bone architecture is structurally optimized to align with habitual mechanical stress pathways, and highlight the dominant role of trabecular plates in governing the mechanical competence of cancellous bone.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"206 ","pages":"Article 117817"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116387","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":"Alterations in osteocyte mechanostimulation within trabecular-lacunar cavities of human bone from intact to implanted cases: a multiscale model elucidating the role of osteocyte mechanosensors","authors":"Abhisek Gupta ,&nbsp;Masud Rana ,&nbsp;Apurba Das ,&nbsp;Amit Roy Chowdhury ,&nbsp;Nico Verdonschot","doi":"10.1016/j.bone.2026.117784","DOIUrl":"10.1016/j.bone.2026.117784","url":null,"abstract":"<div><div>Osteocytes, being embedded within the bone, sense mechanical stimuli through their various mechanosensors under physiological loading. However, the insertion of metallic implants alters the local mechanical environment, potentially disrupting osteocyte stimulation and affecting bone remodelling, particularly in the peri-implant cancellous bone. To quantify the changes in osteocyte mechanostimulation from the intact to the implanted state and to explore the potential of optimized implants in restoring these stimulations, a three-level multiscale modelling approach was developed. This approach transferred boundary conditions from the global femur (intact or implanted) to a trabecular-level model and subsequently to a cellular-level model. At the cellular level, the osteocyte was modelled within its interstitial fluid and surrounding bone matrix, with a specific focus on its various mechanosensors, aiming to examine quantitative changes in their mechanostimulation before and after implantation. The results showed that osteocyte stimulation in the peri-implant cancellous bone decreased by nearly 60–75% after inserting a solid implant, depending on whether the region corresponded to low or high marrow cell stimulation as defined by fluid shear stress on the trabecular surface. The simulation appeared to be sensitive to a change of implant design showing a recovery of this stimulation of approximately 5% when an optimized porous implant was employed, particularly enhancing osteocyte response near high shear stress regions on the trabecular surface. This study provides a mechanobiological explanation for altered bone remodelling around implants and demonstrates how an optimized implant design can enhance osteocyte stimulation and improve remodelling outcomes.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117784"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949506","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":"Development of a novel anthropomorphic bone phantoms for mimicking osteoporosis in medical imaging development","authors":"Jingrui Hu ,&nbsp;Junning Chen ,&nbsp;Steve Wells ,&nbsp;Karen Knapp","doi":"10.1016/j.bone.2026.117803","DOIUrl":"10.1016/j.bone.2026.117803","url":null,"abstract":"<div><div>Osteoporosis (OP) is characterised by loss of bone mineral density (BMD) and deterioration of trabecular microarchitecture, yet routine clinical imaging techniques remain limited in their ability to fully characterise bone microarchitecture. As new imaging technologies are developed, the potential for point of care bone assessment with both density and microarchitectural parameters of bone becomes a reality. Although advanced imaging modalities such as high-resolution peripheral quantitative computed tomography (HR-pQCT) offers improved sensitivity to bone structure, this is primarily focused on research settings. The development of higher resolution digital tomosynthesis (DT), required rethinking of phantoms, otherwise development and pre-clinical validation are constrained by the lack of reproducible, structure-controlled reference standards. In this study, we present a novel anthropomorphic bone phantom designed as a preclinical platform for calibration, benchmarking, and validation of bone imaging systems and quantitative analysis methods. The phantom integrates digital-twin trabecular models derived from micro-computed tomography (μ-CT), enabling parametric control of trabecular thickness and bone volume fraction to represent healthy and osteoporotic conditions. BMD is independently controlled using calibrated contrast agent (PVP-BaSO₄), while moulded lean and adipose soft-tissue equivalents are incorporated to provide realistic X-ray attenuation for projection-based imaging. The phantoms were evaluated using multiple imaging modalities, including X-ray, DXA, pQCT, DT, and μCT, to verify their fidelity in reproducing both BMD and trabecular microstructural features. Imaging-derived parameters showed strong correlations with controlled variations in trabecular architecture and BMD, demonstrating the utility of the phantom as a source of controlled ground truth for cross-modality comparison. This reproducible platform enables systematic evaluation of imaging systems and facilitates early osteoporosis detection by bridging structure-density relationships. Our phantom serves as a valuable tool for preclinical diagnostic validation, imaging quality assurance, and the development of bone health biomarkers, thereby reducing reliance on animal or cadaveric studies.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117803"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146032024","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":"Modeling rare genetic skeletal disorders with bone organoids: a narrative review","authors":"Dimitra Micha ,&nbsp;Sandra Escalante Quirós ,&nbsp;Elisabeth Marelise W. Eekhoff ,&nbsp;Vivi M. Heine ,&nbsp;Jae-Hyuck Shim ,&nbsp;Lidiia Zhytnik","doi":"10.1016/j.bone.2026.117799","DOIUrl":"10.1016/j.bone.2026.117799","url":null,"abstract":"<div><div>Rare genetic skeletal disorders (RGSDs) encompass a heterogeneous group of hundreds rare conditions affecting the skeletal system. The rarity of these disorders, phenotypic and genetic diversity, combined with the limitations of conventional cellular and animal RGSD models, have hindered progress in understanding their pathophysiology and developing effective therapies. However, the latest advances in stem cell and bone tissue engineering techniques offer transformative opportunities in investigation of RGSD, particularly through bone organoids that enable disease modeling within a precision medicine framework.</div><div>This review outlines the progress in RGSD organoid research, starting with the pivotal concepts of RGSDs bone biology, and extending to the disease-specific molecular signatures essential for selecting cell sources, biomaterials, and biofabrication strategies to improve the translational relevance of the models. We critically evaluate existing bone organoid models for osteogenesis imperfecta, hypophosphatasia, fibrous dysplasia, Gaucher disease, and other representative RGSDs. Finally, we consider ethical implications of animal-free and patient-centric organoid research.</div><div>By integrating the latest advancements in RGSD biology and organoid research, this review outlines how molecular pathophysiology can guide organoid design and highlights key methodological advances that could accelerate therapeutic discovery and progress in precision skeletal medicine.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117799"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146013171","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":"Development of a deep learning-based histological evaluation model for critical-size bone defect healing in rats – an objective tool","authors":"J. Neijhoft ,&nbsp;W. Virefléau ,&nbsp;Y. Zhao ,&nbsp;S. Bianconi ,&nbsp;R. Verboket ,&nbsp;C. Hoog Antink ,&nbsp;I. Marzi ,&nbsp;D. Henrich","doi":"10.1016/j.bone.2026.117791","DOIUrl":"10.1016/j.bone.2026.117791","url":null,"abstract":"<div><h3>Introduction</h3><div>Critical-size femoral defects in rats are a well-established model for preclinical bone regeneration research. Histological evaluation is essential for assessing healing but remains time-consuming and subject to observer variability. Machine learning, particularly convolutional neural networks (CNNs), offers potential for objective and scalable analysis of histological sections.</div></div><div><h3>Materials and methods</h3><div>We developed a modified U-Net model to perform semantic segmentation and classification of bone healing stages based on Movat pentachrome-stained histological sections (<em>n</em> = 669). Five tissue classes (bone, cartilage, bone marrow, granulation tissue, background) were manually annotated to train the model. Data were split into training (64%), validation (16%), and test (20%) sets. The model then was used to segment and rank histological images. In addition, a subset of 20 independent test images was scored by four orthopedic experts, seven medical students, and the AI using a refined bone healing score ranging from −10 to +10.</div></div><div><h3>Results</h3><div>The model achieved high segmentation performance, particularly for bone and background. AI-generated healing scores showed strong correlation with expert ratings (Spearman <em>r</em> = 0.819, <em>p</em> &lt; 0.0001) and similar accuracy to student ratings (mean absolute deviation: AI = 0.468 vs. students = 0.469; <em>p</em> = 0.5753). ICC analysis confirmed excellent agreement between AI and experts (ICC = 0.820) and revealed a significant difference favoring AI over students (bootstrap <em>p</em> = 0.0466).</div></div><div><h3>Conclusion</h3><div>This study introduces a CNN-based model capable of expert-level performance in the histological assessment of bone healing. It offers a reproducible and time-efficient tool for future preclinical applications.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117791"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961072","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":"Sclerostin-targeted delivery of PCSK9 siRNA reverses osteoporosis in OVX mice","authors":"Hongling Wu ,&nbsp;Liyuan Huang ,&nbsp;Fangfang Song ,&nbsp;Yueli Zhou ,&nbsp;Yanru Wu ,&nbsp;Jiqi Zheng ,&nbsp;Zhengrong Yin ,&nbsp;Yanyang Wei ,&nbsp;Hualing Sun ,&nbsp;Cui Huang","doi":"10.1016/j.bone.2026.117808","DOIUrl":"10.1016/j.bone.2026.117808","url":null,"abstract":"<div><div>The role of PCSK9 in bone metabolism has recently emerged as a critical area of research. This study identifies a significant upregulation of PCSK9, approximately 1.2-fold in ovariectomized (OVX) mice serum, approximately 3-fold in OVX mice bone marrow stem cells, which correlates strongly with decreased bone mineral density, implicating PCSK9 in estrogen deficiency-induced bone loss. Genetic knockout of PCSK9 was found to ameliorate osteoporosis by improving bone microarchitecture, increasing trabecular bone volume fraction (BV/TV) by 50%, enhancing bone formation (serum PINP increased by 30%), and bone resorption (serum β-CTX increased by 10%), confirming its dual regulatory function. Based on these findings, we engineered a bone-targeted exosome delivery system by surface functionalizing exosomes with an anti-sclerostin (anti-SCL) fragment. This novel system facilitated efficient bone-specific enrichment (fluorescence intensity in bone increased by 60%) and the successful delivery of siPCSK9, resulting in potent silencing of bone marrow PCSK9 expression. In OVX osteoporotic mice, this targeted intervention markedly attenuated bone loss. A 2-fold increase in bone mass was observed relative to the untreated OVX group. Our work not only elucidates a pivotal role of PCSK9 in osteoporosis pathogenesis but also provides a compelling proof-of-concept for exosome-based precision therapy, offering substantial potential for clinical translation.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117808"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073967","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":"Does lumbar vertebra bone microstructure relate to combined loading fracture tolerance and inform fracture initiation site?","authors":"Sophia K. Tushak ,&nbsp;Pavel Chernyavskiy ,&nbsp;Bay Gates ,&nbsp;Christina George ,&nbsp;Jason R. Kerrigan","doi":"10.1016/j.bone.2026.117806","DOIUrl":"10.1016/j.bone.2026.117806","url":null,"abstract":"<div><div>Lumbar vertebrae bone microstructure has been shown to correlate to compressive mechanical properties and display regional variability. However, properties quantified using bone samples may be dissimilar to those of the entire vertebra and sensitive to test methods. Additionally, significant differences in bone quantity across regions of lumbar vertebrae may assist in identifying fracture initiation sites. Further, most studies consider uniaxial compressive loading, whereas the in vivo spine experiences combined loading. The goal of the study was to quantify the relationship between human lumbar vertebrae microstructure and its fracture tolerance to combined compression and flexion. A second goal was to assess if significant regional variation of microstructure within the vertebral body could suggest a location for fracture initiation, given the relationship between microstructure and fracture tolerance. Human three-vertebra spine sections were exposed to dynamic compression-flexion loading, and then the center vertebral bodies were isolated and imaged via micro-computed tomography. Commercial evaluation software was used to quantify bone volume fraction (BV/TV) and cortical thickness (Ct.Th). Bayesian statistical analyses were performed to relate bone microstructure to fracture tolerance with age as a covariate and to quantify microstructural regional variation. BV/TV was significantly associated with fracture tolerance. For the typical donor at the average age, both BV/TV and Ct.Th were positively correlated to fracture tolerance. Ct.Th was region-dependent, while BV/TV was homogeneous. Further efforts may include identifying correlates for bone microstructure that can be measured from common clinical imaging modalities to aid in developing a practical predictive model.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117806"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146101256","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}