Bone最新文献

{"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":"2026-01-20","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":"Nutraceuticals in orthopedic implant osseointegration: Mechanisms, evidence, and clinical perspectives","authors":"Gabriele Ricciardi ,&nbsp;Domenico Donadio ,&nbsp;Giovanni Ficarra ,&nbsp;Chiara Nasso ,&nbsp;Pietro Foglia ,&nbsp;Alessandra Bitto ,&nbsp;Rosa Scarfì ,&nbsp;Guido Fadda ,&nbsp;Flavio Corpina ,&nbsp;Erica Cutè ,&nbsp;Maurizio Martini ,&nbsp;Marco Ferlazzo","doi":"10.1016/j.bone.2026.117801","DOIUrl":"10.1016/j.bone.2026.117801","url":null,"abstract":"<div><div>Total joint replacement is one of the most successful interventions in modern orthopedics, but long-term outcomes depend on effective osseointegration. Pharmacological strategies such as bisphosphonates, estrogens, and monoclonal antibodies can enhance bone–implant integration, but their clinical use is limited by adverse effects. Nutraceuticals, including polyphenols, carotenoids, and polyunsaturated fatty acids, have emerged as promising adjuncts to support bone health and osseointegration, thanks to their safety profile and biological activity. This review summarizes the molecular mechanisms involved in osseointegration, analyzes preclinical and clinical evidence on nutraceuticals, and critically assesses their translational potential. These compounds promote osteoblastogenesis, inhibit osteoclast differentiation, and mitigate oxidative stress, thereby improving peri-implant bone stability. Despite encouraging results, the clinical translation of nutraceuticals remains limited. Most available data are preclinical or based on surrogate endpoints such as bone mineral density, whereas true clinical success is determined by bone-to-implant contact and implant survival, which are rarely investigated in randomized controlled trials (RCTs). Advances in bioavailability strategies (liposomes, nanoemulsions, nanostructured lipid carriers) may improve systemic exposure, but future research must standardize dosages and provide high-quality RCTs to clarify the role of nutraceuticals as complementary tools in orthopedic implant surgery.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117801"},"PeriodicalIF":3.6,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146032050","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":"Improvements in bone quality by parathyroid hormone treatment are enhanced in the Nmp4 knockout mouse model","authors":"Runkang Chen ,&nbsp;Bowen Wang ,&nbsp;Samuel J. Stephen ,&nbsp;Joseph P. Bidwell ,&nbsp;Deepak Vashishth","doi":"10.1016/j.bone.2026.117800","DOIUrl":"10.1016/j.bone.2026.117800","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Osteoporosis is linked to increased bone fragility. Unlike anti-resorptive therapies, the analogue of parathyroid hormone, PTH &lt;span&gt;&lt;span&gt;[1]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[2]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[3]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[4]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[5]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[6]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[7]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[8]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[9]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[10]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[11]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[12]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[13]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[14]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[15]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[16]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[17]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[18]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[19]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[20]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[21]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[22]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[23]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[24]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[25]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[26]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[27]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[28]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[29]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[30]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[31]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[32]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[33]&lt;/span&gt;&lt;/span&gt;, &lt;span&gt;&lt;span&gt;[34]&lt;/span&gt;&lt;/span&gt;, is an FDA-approved therapeutic for osteoporosis that enhances bone formation. However, as PTH treatment potency declines over time, it is necessary to investigate the mechanisms involved in this attenuation to reinforce its long-term efficacy. This need has led to investigations into the transcription factor nuclear matrix protein 4 (&lt;em&gt;Nmp4&lt;/em&gt;), in which PTH treatment of mice globally lacking &lt;em&gt;Nmp4&lt;/em&gt; (&lt;em&gt;Nmp4&lt;/em&gt;&lt;sup&gt;&lt;em&gt;−/−&lt;/em&gt;&lt;/sup&gt;) enhanced bone formation. Yet, the changes in the compositional quality of PTH-stimulated bone in &lt;em&gt;Nmp4&lt;/em&gt;&lt;sup&gt;&lt;em&gt;−/−&lt;/em&gt;&lt;/sup&gt; mice are unknown, which in turn could impact the efficiency of this approach. To this end, we characterized cortical bone quality in &lt;em&gt;Nmp4&lt;/em&gt;&lt;sup&gt;&lt;em&gt;−/−&lt;/em&gt;&lt;/sup&gt; mice and wild-type littermates treated with PTH for 8 weeks, starting at 16 weeks of age, using micro-computed tomography, Raman spectroscopy, X-ray diffraction, biochemical assays, and biomechanical characterization (whole-bone strength, fracture toughness). PTH treatment and &lt;em&gt;Nmp4&lt;/em&gt; ablation increased tissue and marrow area and maximum moment of inertia. Femora from PTH-treated mice exhibited increased stiffness, maximum load, and fracture resistance. Bone in &lt;em&gt;Nmp4&lt;/em&gt;&lt;sup&gt;&lt;em&gt;−/−&lt;/em&gt;&lt;/sup&gt; mice with PTH treatment demonstrated lower mineral crystallinity, decreased mineral-to-matrix ratio, lattice spacing, altered levels of advanced glycation end-products, increased levels of osteocalcin, and increased matrix phosphorylation levels. These results suggest that ablation of &lt;em&gt;Nmp4,&lt;/em&gt; in concert with PTH treatment, improved bone function by modulating bone structure and matrix composition. Our findings demonstrate the potential utility of targeting &lt;em&gt;Nmp4&lt;/em&gt; to improve PTH potency and bone qual","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117800"},"PeriodicalIF":3.6,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020961","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":"2026-01-18","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":"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":"2026-01-16","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":"Prmt1-mediated methylation of Ddx17 promotes osteoblast differentiation via regulating the alternative splicing of Sh2b1","authors":"Xinluan Jiang ,&nbsp;Bilan Li ,&nbsp;Yunfei Ma ,&nbsp;Jiaxin Huang ,&nbsp;Chengwei Gu ,&nbsp;Yucui Jin ,&nbsp;Huimin Ding ,&nbsp;Changyan Ma","doi":"10.1016/j.bone.2026.117798","DOIUrl":"10.1016/j.bone.2026.117798","url":null,"abstract":"<div><div>Osteoporosis (OP) is characterized by impaired osteoblast-mediated bone formation and reduced mineralization, which increases fracture risk and challenges global skeletal health. Ddx17 (DEAD-box helicase 17) is implicated in multiple cancers, but its role and mechanism in bone biology, especially in osteoblast differentiation and osteoporosis pathogenesis remain unclear. In this study, we demonstrated that Ddx17 expression was significantly reduced in trabecular bones of patients with osteoporosis. During osteoblastic differentiation of MC3T3-E1 and C3H10T1/2 cells, Ddx17 expression levels increased gradually in a time-dependent manner. Loss-of-function and gain-of-function experiments revealed that Ddx17 promoted osteoblast proliferation and differentiation. Mechanistically, Ddx17 was a direct substrate of Prmt1 (protein arginine methyltransferase 1), which specifically catalyzed ADMA modification of Ddx17 at R426, thereby enhancing Ddx17 protein stability. Stabilized Ddx17 modulated the alternative splicing of Sh2b1 mRNA, thereby promoting the expression of Sh2b1-T1 while suppressing that of Sh2b1-T2. Rescue experiments demonstrated that re-expression of Sh2b1-T1, but not Sh2b1-T2, reversed the impairment of osteoblast differentiation triggered by Ddx17 knockdown. Taken together, these findings underscore the critical role of the Prmt1-Ddx17-Sh2b1 axis in regulating osteoblast differentiation and suggest this axis as a promising therapeutic target for osteoporosis.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117798"},"PeriodicalIF":3.6,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974056","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":"Osteoblastic cell responses to zoledronate treatment in-vitro: A systematic review","authors":"Maria Florez-Martin,&nbsp;Adriana-Monica Radu,&nbsp;Kaveh Shakib,&nbsp;Gavin Jell","doi":"10.1016/j.bone.2026.117796","DOIUrl":"10.1016/j.bone.2026.117796","url":null,"abstract":"<div><h3>Background:</h3><div>Zoledronate (ZOL), a potent nitrogen-containing bisphosphonate (BP), is widely prescribed for osteoporosis and metastatic bone disease. While osteoclast inhibition is central to ZOL’s therapeutic action and to the pathophysiology of medication-related osteonecrosis of the jaw (MRONJ), less is known about its direct effects on osteoblasts. Understanding dose- and time-dependent osteoblastic responses is essential for improving <em>in-vitro</em> modelling and informing regenerative strategies.</div></div><div><h3>Methods:</h3><div>We performed a systematic review of <em>in-vitro</em> studies reporting osteoblastic responses to ZOL, adhering to PRISMA guidelines (protocol registered, DOI:10.17605/OSF.IO/GWDP5). Web of Science and Scopus searches identified 606 records, of which 77 met inclusion criteria. Data were extracted for proliferation, metabolic activity, apoptosis, alkaline phosphatase (ALP), biomineralisation, collagen formation, and angiogenesis. Statistical comparisons assessed dose- and time-dependent effects.</div></div><div><h3>Results:</h3><div>Across 2057 datapoints, undesirable outcomes (reduced metabolic activity or proliferation, increased apoptosis) occurred at median [ZOL] of 10 <span><math><mi>μ</mi></math></span>M, significantly higher (<span><math><mrow><mi>p</mi><mo>≤</mo><mn>0</mn><mo>.</mo><mn>0001</mn></mrow></math></span>) than concentrations associated with no effect (1 <span><math><mi>μ</mi></math></span>M) or beneficial responses (0.75 <span><math><mi>μ</mi></math></span>M). Desirable nanomolar-dose outcomes were infrequent and inconsistent across studies. ALP and biomineralisation were dose-dependently impaired, whereas collagen synthesis was unaffected. At 48–71 h, osteoblasts tolerated higher ZOL concentrations compared to later timepoints (<span><math><mrow><mi>p</mi><mo>≤</mo><mn>0</mn><mo>.</mo><mn>05</mn></mrow></math></span>). Media composition influenced responses, with higher calcium (<span><math><mo>≥</mo></math></span>1.8 mM) media protective of negative effects, likely due to ZOL–Ca complex formation.</div></div><div><h3>Conclusion:</h3><div>ZOL exerts direct, dose-dependent inhibitory effects on osteoblasts <em>in-vitro</em>, with outcomes influenced by exposure time and media composition. This review highlights the need for standardised protocols and provides quantitative guidance for modelling MRONJ and testing regenerative interventions.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117796"},"PeriodicalIF":3.6,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974431","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":"Combined antiresorptive and antiangiogenic therapy versus antiresorptive monotherapy: Impact on the surgical prognosis of MRONJ patients with advanced malignancies","authors":"Yiwen Zou ,&nbsp;Ning Zhao ,&nbsp;Hongyuan Huang ,&nbsp;Ying Zhou ,&nbsp;Yuanning Yang ,&nbsp;Qiao Qiao ,&nbsp;Qingxiang Li ,&nbsp;Jianhua Zhu ,&nbsp;Yifei Wang ,&nbsp;Yuxing Guo","doi":"10.1016/j.bone.2026.117795","DOIUrl":"10.1016/j.bone.2026.117795","url":null,"abstract":"<div><div>For patients with advanced cancer and bone metastasis, antiresorptive medications (ARMs) and antiangiogenic medications (AGMs) are commonly employed to manage tumor progression and skeletal complications. This study evaluates the effects of distinct pharmacotherapeutic strategies—ARM monotherapy versus ARM+AGM combined therapy on surgical outcomes of medication-related osteonecrosis of the jaw (MRONJ) in this population.</div><div>A retrospective cohort analysis was conducted on 157 patients: 106 received ARM monotherapy, and 51 underwent combined ARM+AGM treatment. Demographic data, MRONJ clinical characteristics, and quality of life (QoL) metrics were systematically collected and analyzed using univariate and multivariate statistical methods.</div><div>Univariate analysis revealed that the ARM group had a higher proportion of females, longer antiresorptive therapy duration, and more favorable outcomes, including reduced postoperative pain and improved QoL compared to the ARM+AGM group. Multivariate analysis demonstrated that the ARM+AGM group exhibited a 2.8-fold recurrence risk relative to the ARM group, with prognosis significantly influenced by medication strategy, disease stage, and surgical approach.</div><div>These findings indicate that combined ARM+AGM therapy is associated with a poorer prognosis and heightened recurrence risk in MRONJ patients compared to ARM monotherapy.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117795"},"PeriodicalIF":3.6,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992184","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":"2026-01-13","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":"Integrated methylome and hydroxymethylome analysis identifies CAMK2G, NFATC4, and SFRP2 as TET1-regulated drivers of odontoblastic differentiation in human dental pulp cells","authors":"Qimeng Li ,&nbsp;Jinling Li ,&nbsp;Deqian Zhang ,&nbsp;Qiong Xu","doi":"10.1016/j.bone.2026.117775","DOIUrl":"10.1016/j.bone.2026.117775","url":null,"abstract":"<div><h3>Aim</h3><div>DNA 5-methylcytosine (5mC) dynamics are pivotal for tooth differentiation. However, the 5mC landscape during human dental pulp cell (hDPCs) odontoblastic differentiation and the role of Ten-eleven translocation 1 (TET1)-mediated 5mC regulation remain unclear. This study aimed to characterize methylation dynamics and identify TET1-regulated drivers of odontoblastic differentiation.</div></div><div><h3>Methodology</h3><div>Genome-wide DNA methylation was profiled by microarray, and hydroxymethylation changes after TET1 knockdown were assessed by hMeDIP-seq.</div></div><div><h3>Results</h3><div>Methylation and demethylation maintained a dynamic equilibrium during odontoblastic differentiation. A total of 9752 differentially methylated genes were identified and were enriched in pathways related to mesenchymal stem cell and ameloblast differentiation and neurotrophin signaling. hMeDIP-seq demonstrated that TET1 knockdown in hDPCs resulted in 2237 peaks with decreased 5-hydroxymethylcytosine (5hmC) levels and 3285 peaks with increased 5hmC levels compared to controls, corresponding to 1477 hypo-hydroxymethylated genes and 1905 hyper-hydroxymethylated genes. Integrated analysis of hypo-methylated genes and hypo-hydroxymethylated genes identified 88 overlapping candidates. Functional enrichment analyses highlighted tooth mineralization, osteoblast differentiation, TGF-β, and Wnt pathways. Among these, CAMK2G, NFATC4, and SFRP2 were specifically enriched in Wnt signaling and exhibited reduced 5hmC levels after TET1 knockdown. scRNA-seq data further confirmed increased expression of these three genes during odontoblast differentiation.</div></div><div><h3>Conclusions</h3><div>This study delineated the genome-wide DNA methylation landscape during odontoblastic differentiation and identifies CAMK2G, NFATC4, and SFRP2 as novel TET1-regulated epigenetic drivers via 5hmC modification. These findings highlight potential therapeutic targets for epigenetic intervention in dentin regeneration and dental tissue engineering.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"205 ","pages":"Article 117775"},"PeriodicalIF":3.6,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986084","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}