Bone最新文献

{"title":"Site-specific inverse associations between FGF23 levels and marrow adiposity content at the proximal femur in post-menopausal women","authors":"Paccou Julien ,&nbsp;Badr Sammy ,&nbsp;Ramdane Nassima ,&nbsp;Michou Laetitia ,&nbsp;Courbon Guillaume ,&nbsp;Mentaverri Romuald","doi":"10.1016/j.bone.2026.117813","DOIUrl":"10.1016/j.bone.2026.117813","url":null,"abstract":"<div><h3>Context</h3><div>Experimental studies have suggested that the autocrine/paracrine effects of bone-derived Fibroblast Growth Factor 23 (FGF23) inhibit adipogenesis and promote osteoblastic differentiation of bone marrow stroma cells.</div></div><div><h3>Objective</h3><div>To examine whether there is relationship between circulating levels of FGF23 and bone marrow adiposity assessed by MRI.</div></div><div><h3>Design</h3><div>This cross-sectional study included 199 postmenopausal women without apparent disorders in phosphate homeostasis.</div></div><div><h3>Setting</h3><div>University Hospital of Lille, France.</div></div><div><h3>Main outcome measure(s)</h3><div>C-terminal FGF23 (cFGF23, relative units (RU)/ml) and intact FGF23 (iFGF23, pg/ml). The Proton Density Fat Fraction (PDFF) of the lumbar spine and the proximal femur was assessed using MRI with chemical shift-based water-fat separation (WFI) and DXA of the hip and spine. Our main goal was to explore the relationships between PDFF, cFGF23, and iFGF23 levels in women who are postmenopausal. The relationships between cFG23, iFGF23, and body composition metrics were subsequently analyzed.</div></div><div><h3>Results</h3><div>A significant positive correlation was observed between cFGF23 and iFGF23 (<em>R</em> = 0.534, <em>p</em> &lt; 0.0001). Significant inverse associations were found between cFGF23, iFGF23, and femoral neck PDFF (reciprocally, coefficient β (95%CI), −1.35 (−2.49 to −0.21), <em>p</em> = 0.020 and − 1.66 (−3.00 to −0.32), <em>p</em> = 0.016) after adjustment for age, recent fragility fracture, BMI, eGFR, and BMD. Conversely, there were no notable associations identified between cFGF23, iFGF23, and lumbar spine PDFF, regardless of whether adjustment models were applied. No significant associations were found between cFGF23, iFGF23, and body composition parameters (total body fat and visceral adipose tissue).</div></div><div><h3>Conclusions</h3><div>An inverse association was found between cFGF23, iFGF23, and proximal femur PDFF (particularly femoral neck PDFF), but not with lumbar spine PDFF. Moreover, cFGF23 and iFGF23 levels were not associated with other adipose deposits.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117813"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146097743","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":"Clec4a2 deficiency promotes post-fission osteoclast cell death and suppresses acute inflammation-induced bone loss in the mouse","authors":"Hirofumi Fujita ,&nbsp;Yuma Tai ,&nbsp;Kenji Takahashi ,&nbsp;Yuto Ueda ,&nbsp;Wakana Kitagawa ,&nbsp;Mitsuaki Ono ,&nbsp;Toshitaka Oohashi ,&nbsp;Hideyo Ohuchi","doi":"10.1016/j.bone.2026.117797","DOIUrl":"10.1016/j.bone.2026.117797","url":null,"abstract":"<div><div>To achieve efficient bone resorption by osteoclasts, the specialized innate immune cells, it is important not only to promote osteoclast differentiation and activation but also to maintain their survival. C-type lectin (CLEC) receptors recognize pathogen ligands and altered self-tissues, comprising activating and inhibitory types whose balance eliminates pathogens while preventing excessive immune responses. However, roles of CLEC receptors in osteoclast differentiation, function, and survival remain unclear. We established knockout (KO) mice of CLEC receptor genes highly expressed by osteoclast and analyzed osteoclast features and bone morphology. We conducted comprehensive in silico screening of osteoclast lineage-specific CLEC receptors utilizing a mouse gene expression dataset and generated single and double KO (DKO) mice of <em>Clec4a2</em> and <em>Clec4d</em> using a multi-targeted CRISPR-Cas9 system. <em>Clec4a2</em> KO <em>and</em> DKO enhanced osteoclast differentiation in vitro, and <em>Clec4a2</em> KO also stimulated enlargement of osteoclasts. <em>Clec4d</em> KO slightly reduced trabecular bone thickness in the femur, while <em>Clec4a2</em> KO and DKO did not affect bone morphology under physiological conditions. Contrary to conventional understanding that enhanced osteoclast differentiation leads to increased bone resorption, our time-lapse analysis revealed that <em>Clec4a2</em> KO paradoxically increased osteoclast formation while reducing resorption efficiency due to cell death of osteoclasts and its daughter cells after fission. <em>Clec4a2</em> KO provided protection against inflammatory bone loss induced by lipopolysaccharide, demonstrating the first evidence that Clec4a2 could serve as therapeutic targets for inflammatory osteolytic diseases. This study introduces a novel paradigm that osteoclast survival regulation by Clec4a2 is fundamental for efficient bone resorption.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117797"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000245","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 analysis of osseointegration of glass fiber-reinforced composite-bioactive glass cranial implants","authors":"Vita M. Klieverik ,&nbsp;Marvick S.M. Muradin ,&nbsp;N. Nicolai ,&nbsp;J. Kortes ,&nbsp;Pierre A. Robe ,&nbsp;Peter A. Woerdeman","doi":"10.1016/j.bone.2026.117790","DOIUrl":"10.1016/j.bone.2026.117790","url":null,"abstract":"<div><h3>Background</h3><div>Glass fiber-reinforced composite-bioactive glass (FRC-BG) implants are emerging as an alternative to autologous bone grafts with the potential for new bone formation and ingrowth from the surrounding skull. However, clinical evidence of osseointegration remains to be demonstrated.</div></div><div><h3>Objective</h3><div>To evaluate radiological measures of osseointegration of FRC-BG implants used for cranioplasty.</div></div><div><h3>Methods</h3><div>A retrospective cohort study was conducted including adult patients who underwent cranioplasty with FRC-BG implants between 2016 and 2021. Sequential non-contrast head CT-scans were obtained within 24 h postoperatively and after one year of follow-up. Using three-dimensional (3D) segmentation and analysis software, changes in bone volume (in cm³) and bone density (in Hounsfield units [HU]) of a standardized one cm-wide region of skull bone surrounding the margins of the FRC-BG implants were quantified. Paired samples <em>t</em>-tests assessed differences between baseline and after one year of follow-up.</div></div><div><h3>Results</h3><div>A total of 38 patients were included (mean age 50.2 ± 18.4 years). After one year of follow-up, significant increases were observed in both skull bone volume (mean difference 6.04 cm³, 95% confidence interval [CI] 4.65–7.43, <em>p</em> &lt; 0.001) and skull bone density (mean difference 45.84 HU, 95% CI 1.15–90.52, <em>p</em> = 0.045) surrounding the FRC-BG implants.</div></div><div><h3>Conclusion</h3><div>The present study shows radiological signs of osseointegration of FRC-BG implants used for cranioplasty.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117790"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961079","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":"Electroacupuncture remodels brain functional connectivity and improves bone metabolism in ovariectomized rats","authors":"Lu Zhang ,&nbsp;Yi Rong ,&nbsp;Xiaoxue Wang ,&nbsp;Yanan Chen ,&nbsp;Maoting Xu ,&nbsp;Cai Tang ,&nbsp;Yuan Yang ,&nbsp;Guiquan Chen ,&nbsp;Sheng Li","doi":"10.1016/j.bone.2025.117774","DOIUrl":"10.1016/j.bone.2025.117774","url":null,"abstract":"<div><div>Electroacupuncture has demonstrated established efficacy in treating postmenopausal osteoporosis, yet the central mechanisms underlying its action via the brain-bone axis remain incompletely understood. This study employed multimodal resting-state functional magnetic resonance imaging to investigate neurofunctional changes induced by electroacupuncture in a rat model of postmenopausal osteoporosis. Twenty-four female Sprague-Dawley rats were randomly allocated to electroacupuncture, sham, and model (ovariectomized) groups. The electroacupuncture group received an 8-week intervention at acupoints GB30, GB34, and GB39. We assessed brain function through amplitude of low-frequency fluctuation, regional homogeneity, and region-of-interest functional connectivity, while simultaneously measuring serum bone turnover markers via enzyme-linked immunosorbent assay. Our results demonstrated that electroacupuncture significantly improved bone microstructure and reduced bone resorption marker levels. Neuroimaging revealed enhanced cerebellar neural activity which correlated negatively with bone resorption, alongside decreased neural synchronization in the entorhinal cortex. Furthermore, strengthened functional connectivity between entorhinal and visual cortices positively correlated with bone formation markers, while weakened somatosensory-cerebellar connectivity correlated with reduced bone resorption. Bayesian mediation analysis provided strong statistical evidence for the role of the entorhinal-visual pathway involvement in bone formation regulation and cerebellar mediation of bone resorption suppression. These findings systematically reveal the association between electroacupuncture-induced brain functional reorganization and bone metabolic improvements, offering new insights into the role of the brain-bone axis in osteoporosis management.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117774"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992169","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":"Cellular alterations in trabecular bone following monocrotaline-induced right heart failure in rats","authors":"Akinori Kaneguchi,&nbsp;Rena Takagi,&nbsp;Sakura Sunagawa,&nbsp;Yuichiro Azuma,&nbsp;Koki Ishinaka,&nbsp;Takuya Umehara,&nbsp;Kaoru Yamaoka,&nbsp;Junya Ozawa","doi":"10.1016/j.bone.2026.117807","DOIUrl":"10.1016/j.bone.2026.117807","url":null,"abstract":"<div><div>Heart failure is associated with bone deterioration, consequently increasing the risk of fractures. Fractures occurring in patients with heart failure are associated with increased hospitalization and mortality rates, making the prevention of bone deterioration a critical clinical concern. The cellular alterations associated with heart failure-related bone deterioration remain largely unexplored. This study aimed to investigate histological changes in trabecular bone following heart failure, with a focus on characterizing cellular alterations associated with bone deterioration. Male Wistar rats were assigned to either a control or heart failure group. The heart failure group was administered monocrotaline intraperitoneally, while the control group received a vehicle injection. Twenty-eight days post-injection, histological analyses were conducted on the proximal humerus, proximal femur, distal femur, and proximal tibia. Compared to controls, rats in the heart failure group exhibited a significant reduction in trabecular bone volume at all examined sites. In parallel, they showed a significant increase in the number of osteoclasts, an increased empty lacuna ratio (indicative of osteocyte loss), and a greater proportion of caspase-3–positive osteocytes (a marker of apoptosis). These changes were consistently observed across all anatomical locations. These findings suggest that heart failure induces osteocyte apoptosis, which may drive osteoclastogenesis and lead to trabecular bone loss. The fact that similar changes were observed consistently across all anatomical sites suggests that systemic factors associated with heart failure, rather than localized influences, are likely the primary contributors to bone deterioration. Understanding these processes could inform novel therapeutic strategies to prevent bone loss following heart failure.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117807"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073971","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":"Corrigendum to “Pulsed electromagnetic fields inhibit human osteoclast formation and gene expression via osteoblasts” [Bone 106 (2018) 194–203 (ISSN: 8756-3282)]","authors":"Zhiming He ,&nbsp;Nagarajan Selvamurugan ,&nbsp;Johanna Warshaw ,&nbsp;Nicola C. Partridge","doi":"10.1016/j.bone.2026.117794","DOIUrl":"10.1016/j.bone.2026.117794","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117794"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146032065","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 between systemic redox balance and osteoporosis: prospective evidence, polygenic modification, and proteomic and inflammatory mediation in the UK Biobank","authors":"Yuanpeng Zhu ,&nbsp;Di Liu ,&nbsp;Xiangjie Yin ,&nbsp;Terry Jianguo Zhang ,&nbsp;Nan Wu","doi":"10.1016/j.bone.2026.117802","DOIUrl":"10.1016/j.bone.2026.117802","url":null,"abstract":"<div><h3>Purpose</h3><div>Redox signaling governs bone remodeling, but whether systemic redox balance is associated with incident osteoporosis, genetic susceptibility, and proteomic/inflammatory pathways at population scale remains unclear.</div></div><div><h3>Methods</h3><div>We analyzed UK Biobank participants free of osteoporosis at baseline. Serum redox balance score (SRBS) combined albumin, total bilirubin, and γ-glutamyl transferase. Cox proportional hazards models adjusted for prespecified covariates. Effect modification by an osteoporosis polygenic risk score (PRS) was tested on multiplicative and additive scales. Mediation was evaluated in a proteomics subset and an inflammatory-panel subset using counterfactual mediation with multiple-testing control.</div></div><div><h3>Results</h3><div>Over a median follow-up of 12.8 years (IQR, 11.7–13.7), 12,893 incident osteoporosis cases were observed. SRBS demonstrated a nonlinear inverse association with osteoporosis, displaying a J-shaped pattern: relative to Q1, multivariable hazard ratios (95% CIs) were 0.82 (0.78–0.86) for Q2, 0.75 (0.71–0.78) for Q3, and 0.72 (0.68–0.75) for Q4; the per–standard-deviation increase corresponded to an HR of 0.85 (0.83–0.87). Cumulative-incidence curves diverged early and showed a stepwise gradient across quartiles. Associations were stronger among men and physically inactive participants. SRBS interacted with the osteoporosis PRS on the multiplicative scale (interaction HR, 1.03; 95% CI, 1.02–1.04), whereas evidence for additive interaction was limited. Proteomic mediation implicated EGFR, TNFRSF10A, CBLN4, CD27, and IGDCC4 (≈8–11% each); inflammatory mediation implicated C-reactive protein (≈8%), platelets (≈4%), and neutrophils (≈4%).</div></div><div><h3>Conclusion</h3><div>Systemic redox balance values were linked to osteoporosis risk, with partial mediation through plasma-protein and inflammatory pathways and only modest modification by polygenic risk.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117802"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146032007","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":"o-Vanillin enhances bone health and fracture healing by inhibiting cellular senescence in aging mice","authors":"Xiao Ouyang ,&nbsp;Shuo Geng ,&nbsp;Muhammad Abdullah ,&nbsp;Yan Geng ,&nbsp;Ke Heng ,&nbsp;Liangwei Sha ,&nbsp;Yinuo Geng ,&nbsp;Peiru Nie ,&nbsp;Fanshuo Liu ,&nbsp;Juan Zhai ,&nbsp;Xingchen Song ,&nbsp;Huaiyuan Zhai ,&nbsp;Junli Huang ,&nbsp;Guoqiang Wang ,&nbsp;Rui Geng ,&nbsp;Kui Xue ,&nbsp;Qilong Wang ,&nbsp;Wanying Huang ,&nbsp;Huanyu Zhang ,&nbsp;Ying Geng ,&nbsp;Qinghe Geng","doi":"10.1016/j.bone.2025.117773","DOIUrl":"10.1016/j.bone.2025.117773","url":null,"abstract":"<div><div>Aging is associated with skeletal fragility driven by impaired bone remodeling, increased oxidative stress, and the accumulation of senescent cells. To determine whether ortho-vanillin (o-Vanillin) can alleviate age-related deficits in bone, we examined femoral bone microarchitecture, biomechanical properties, bone turnover, bone marrow adiposity, oxidative stress, DNA damage, osteocyte senescence, and femoral fracture healing in C57BL/6 J mice. DEXA was additionally used to assess bone mineral density and content at the femur, tibia, spine, and whole body. Aged mice displayed substantial deterioration in femoral trabecular and cortical structure, reduced mechanical strength, diminished osteogenic activity, enhanced osteoclastogenesis, and increased marrow adiposity. Aging also elevated oxidative stress, lipid peroxidation, and DNA damage, and induced significant osteocyte senescence with upregulation of SASP factors. o-Vanillin administration attenuated these changes, improving femoral bone microarchitecture and strength, restoring osteoblast function, suppressing osteoclast activity and adipogenesis, reducing oxidative stress and γH2AX accumulation, and decreasing osteocyte senescence and SASP expression. In a mid-diaphyseal femoral fracture model, aged mice exhibited impaired callus formation and delayed healing, whereas o-Vanillin partially improved early cartilage formation, osteoblast activity, and mechanical strength of the healing callus. These findings demonstrate that o-Vanillin mitigates multiple age-related impairments in the femur and partially restores fracture healing capacity, supporting its potential as a senescence-targeting approach to improve skeletal health during aging.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117773"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883387","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":"Hyperbaric oxygen therapy for osteoporosis: A systematic review of preclinical evidence and mechanisms","authors":"Hao Wang ,&nbsp;Xiao Ma ,&nbsp;Yang Sun ,&nbsp;Zhihao Guo ,&nbsp;Jincheng Wang ,&nbsp;Mingli Sun","doi":"10.1016/j.bone.2025.117772","DOIUrl":"10.1016/j.bone.2025.117772","url":null,"abstract":"<div><div>Hyperbaric oxygen therapy (HBOT) has been proposed as a direct anti-osteoporotic intervention rather than solely an adjunctive therapy. We systematically synthesized preclinical in vivo evidence and underlying mechanisms following PRISMA, with prospective registration (PROSPERO CRD42024525038), by searching PubMed, Embase, Cochrane Library, and Web of Science to November 2025. Of 3281 records, six studies (2016–2025) met inclusion across ovariectomy, hindlimb unloading, spinal cord transection, and D-galactose–induced aging models in Wistar and Sprague-Dawley rats. HBOT protocols most used 2.0–2.2 atm absolute with 85–100 % oxygen for 40–60 min per session. Across studies, HBOT improved bone mineral density and trabecular microarchitecture (e.g., BV/TV, Tb.Th, Tb.N), enhanced biomechanical strength, increased formation markers (e.g., procollagen type I N-terminal propeptide, bone-specific alkaline phosphatase, osteocalcin), and reduced resorption markers (e.g., C-terminal telopeptide of type I collagen, tartrate-resistant acid phosphatase-5b). Mechanistic signals converged on remodeling and vascular–metabolic pathways: modulation of the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis; restoration of Wnt/β-catenin signaling with reduced sclerostin; attenuation of oxidative and inflammatory stress (e.g., tumor necrosis factor-α); pro-angiogenic support (vascular endothelial growth factor, basic fibroblast growth factor); and neuropeptide-related effects (calcitonin gene-related peptide). Risk-of-bias profiles were mixed and heterogeneity precluded meta-analysis. Collectively, preclinical data indicate that HBOT mitigates osteoporotic bone loss primarily through coordinated, mechanisms of action that rebalance bone remodeling and improve the osteovascular milieu, while underscoring the need for standardized dosing parameters and rigorously designed human studies powered for clinically meaningful endpoints.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117772"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883386","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 chromosome and gonadal contributions to body composition and skeletal mass and strength in aged four core genotypes (FCG) mice","authors":"Paola Ortiz Gonzalez ,&nbsp;Alix Teal ,&nbsp;Lakshmi Chellaganapathy ,&nbsp;Gabriel Ramirez ,&nbsp;Roquelina Pianeta ,&nbsp;Dyann M. Segvich ,&nbsp;Ziyue Liu ,&nbsp;Joseph M. Wallace ,&nbsp;Lilian I. Plotkin","doi":"10.1016/j.bone.2026.117785","DOIUrl":"10.1016/j.bone.2026.117785","url":null,"abstract":"<div><div>Sex differences in musculoskeletal aging are often attributed to gonadal hormones, but the independent role of sex chromosomes remains unclear. Using the Four Core Genotype mouse model, which dissociates sex chromosomes (XX vs. XY) from gonadal sex (ovaries vs. testes), our goal was to examine sex chromosomes and gonads independent and interactive effects on bone, muscle and organ phenotypes from 8 to 20 months of age in XXO, XYO, XXT, and XYT mice. XYO mice showed high mortality (38.7%-survival by 20 months) when compared with other genotypes (67–86.7%). Between 8 and 20 months, XYO mice showed increases in lean mass and femoral BMD and improved bone structural parameters, yet lower cortical tissue mineral density. XXO mice displayed pronounced late-life gains in body weight, lean and fat mass not observed in other genotypes, although lean mass differed only versus XXT mice at 20 months. Total and spine BMD declined in XXO mice, accompanied with lower structural parameters and higher tissue mineral density than XYO mice. XXT mice displayed bone loss at all skeletal sites, whereas XYT mice showed a selective decline in spine BMD. Overall, chromosome sex adversely affected bone and muscle mass in XX versus XY mice, while gonadal sex influenced bone structure and absolute muscle mass, with mice bearing ovaries generally exhibiting lower muscle mass. Organ weight effects were modest and limited to spleen (XYO &gt; XXO/XYT) and brain (XYT &gt; XXT). Collectively, these findings reveal a previously unrecognized, tissue-specific contribution of sex chromosomes to musculoskeletal aging, independent of gonadal sex.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117785"},"PeriodicalIF":3.6,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954280","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}