Journal of Bone and Mineral Research最新文献

{"title":"Correction to: Vertebral fracture prevalence and risk factors for fracture in The Gambia, West Africa: the Gambian Bone and Muscle Ageing Study.","authors":"","doi":"10.1093/jbmr/zjaf109","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf109","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Denosumab and vascular calcification progression: smoke, but not yet fire.","authors":"Ditte Hansen, Pieter Evenepoel","doi":"10.1093/jbmr/zjaf131","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf131","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycoxidation of the bone matrix modulates mineralization.","authors":"Samuel J Stephen, Grażyna E Sroga, Deepak Vashishth","doi":"10.1093/jbmr/zjaf080","DOIUrl":"10.1093/jbmr/zjaf080","url":null,"abstract":"<p><p>Type 2 diabetes (T2D) is a prevalent condition that is associated with heightened fracture risk despite T2D patients exhibiting normal or elevated BMD. T2D exacerbates oxidative stress and hyperglycemia, which increases the accumulation of advanced glycation end products (AGEs) and advanced glycoxidation end products (AGOEs) in bone. Carboxymethyl-lysine (CML) is one such AGOE linked to fracture risk and could impact bone mineralization due to its carboxyl terminus. Still, the mechanism linking CML to altered mineralization and impaired bone quality in T2D is unknown. To investigate how glycoxidation modulates bone mineralization, sectioned human tibiae (23-yr-old to 89-yr-old donors, Caucasian male [CM] and Caucasian female [CF]) were treated in vitro with glyoxal or ribose to enhance CML content or AGE content. Sections were then suspended between calcium and phosphate solutions to promote mineral growth. Raman spectroscopy revealed that AGE and CML enhancement increased the degree of mineralization and accelerated mineral maturation, with CML-enhanced samples exhibiting the greatest increase in mineral growth. Solid-state nuclear magnetic resonance illustrated that CML enhancement increased the degree of electronegativity in the collagen structure and at the mineral surface, which was associated with increased compressive strain on the mineral platelet as unveiled by X-ray diffraction. Nanoindentation demonstrated lowered hardness and increased work energy in CML-enhanced samples. Collectively, these findings demonstrate a mechanism that links glycoxidation to matrix mineralization. The ability for CML to influence bone mineralization underlines the need to develop strategies to target CML accrual and mitigate fracture risk in patients with T2D.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1165-1176"},"PeriodicalIF":5.9,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144264880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of histone deacetylase 3 in dental mesenchyme regulates the development of tooth root.","authors":"Kunimichi Niibe, Dana L Begun, Kanna Doi-Fujimura, Atsuhiro Nagasaki, Elizabeth Zars, Xiaodong Li, Earnest L Taylor, Mary B MacDougall, Hiroshi Egusa, Jennifer J Westendorf","doi":"10.1093/jbmr/zjaf102","DOIUrl":"10.1093/jbmr/zjaf102","url":null,"abstract":"<p><p>Studies on human and animal models have demonstrated a complex molecular regulatory network between the dental mesenchyme and epithelium governing tooth development. However, epigenetic regulation of tooth development is largely unexplored. This study aimed to elucidate the relationship between epigenetic modifiers and dental root development using mice deficient in histone deacetylase 3 (Hdac3) under the control of the osterix promoter (Osx-Cre/Hdac3fl/fl or Hdac3-CKOosx). We observed tooth root size and histology in Hdac3-CKOosx mice. Dental pulp progenitor cells (DPCs) were isolated from lower incisors, and calcification and gene expression were assessed. Hdac3 depletion in osterix-expressing dental pulp stem cells, including odontoblasts, caused a progressive postnatal obstruction, resulting in relatively short roots and small root apices of the first molar. Mild degeneration was observed during the development of dentin and cementum structures. Dentin and cementum had uneven borders and showed disordered H&E staining in Hdac3-CKOosx mice that had a thin cementum compared to that of WT mice. Hdac3 inhibition/deletion in dental pulp stem cells probably influenced Msh homeobox 1 (Msx1) and Col1a1 expression in the early developmental stage, thereby driving differentiation in DPCs. Subsequently, Msx1, Col1a1, and osteocalcin expression were remarkably downregulated during calcification. Deletion or inhibition of Hdac3 in conditional KO dental pulp stem cells cultured in mineralization medium resulted in aberrant cell cycle control, and the early stages of maturation of DPCs and odontoblasts were inhibited. Inhibition of Hdac3 in cementocytes also restricted their proliferation and calcification. These results suggested that the deletion or inhibition of Hdac3 in the dental mesenchyme may cause development and maturation deficiency of tooth root.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1177-1187"},"PeriodicalIF":5.9,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between physical activity during growth and bone microarchitecture at peak bone mass.","authors":"Annelise G Pageau, Lauren A Burt, Leigh Gabel, Steven K Boyd, Danielle E Whittier","doi":"10.1093/jbmr/zjaf099","DOIUrl":"10.1093/jbmr/zjaf099","url":null,"abstract":"<p><p>Childhood and adolescence are critical periods for skeletal development in establishing peak bone mass (PBM), an important determinant of lifelong fracture risk. This study investigates the relationship between cumulative physical activity during growth and bone density and microarchitecture attained surrounding PBM. BMD and microarchitecture properties were obtained in 226 individuals (142 females; 84 males) surrounding PBM (aged 18-35 years) using HR-pQCT at the distal radius and tibia, and DXA at the lumbar spine and femoral neck. Physical activity during growth up to PBM was captured with the bone-specific physical activity questionnaire (BPAQ). Spearman's partial correlations, adjusted for age, height, and weight were used to determine sex-specific associations between bone properties and physical activity during growth. Higher physical activity during growth quantified by the BPAQ (gBPAQ) was associated with higher tibia failure load and femoral neck areal BMD, in both sexes (ρ = 0.27-0.38, p ≤ .02). Higher gBPAQ scores were also associated with better trabecular BMD and bone volume fraction at the tibia in both sexes, where associations were stronger in males (ρ = 0.40-0.41, p < .01) than in females (ρ = 0.24-0.26, p < .05). Males additionally had significant associations with trabecular bone microarchitecture properties, including number, separation, and inhomogeneity at both the radius (ρ = 0.30-0.34, p ≤ .01) and tibia (ρ = 0.31-0.42, p ≤ .02). In contrast, gBPAQ scores were not associated with cortical bone properties at PBM for either sex or site. Physical activity during growth is associated with greater BMD and failure load at PBM, 2 predictors of lifelong fracture risk. However, compartment-specific differences indicate that trabecular bone, as opposed to cortical bone, is more responsive to physical activity during growth.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1156-1164"},"PeriodicalIF":5.9,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Body mass index and subsequent fracture risk: a meta-analysis to update FRAX.","authors":"Nicholas C Harvey, Helena Johansson, Eugene V McCloskey, Enwu Liu, Kristina E Åkesson, Fred A Anderson, Rafael Azagra-Ledesma, Cecilie L Bager, Charlotte Beaudart, Heike A Bischoff-Ferrari, Emmanuel Biver, Olivier Bruyère, Jane A Cauley, Jacqueline R Center, Roland Chapurlat, Claus Christiansen, Cyrus Cooper, Carolyn J Crandall, Steven R Cummings, José A P da Silva, Bess Dawson-Hughes, Adolfo Diez-Perez, Alyssa B Dufour, John A Eisman, Petra J M Elders, Serge Ferrari, Yuki Fujita, Saeko Fujiwara, Claus-Christian Glüer, Inbal Goldshtein, David Goltzman, Vilmundur Gudnason, Jill Hall, Didier Hans, Mari Hoff, Rosemary J Hollick, Martijn Huisman, Masayuki Iki, Sophia Ish-Shalom, Graeme Jones, Magnus K Karlsson, Sundeep Khosla, Douglas P Kiel, Woon-Puay Koh, Fjorda Koromani, Mark A Kotowicz, Heikki Kröger, Timothy Kwok, Olivier Lamy, Arnulf Langhammer, Bagher Larijani, Kurt Lippuner, Fiona E A McGuigan, Dan Mellström, Thomas Merlijn, Tuan V Nguyen, Anna Nordström, Peter Nordström, Terence W O'Neill, Barbara Obermayer-Pietsch, Claes Ohlsson, Eric S Orwoll, Julie A Pasco, Fernando Rivadeneira, Berit Schei, Anne-Marie Schott, Eric J Shiroma, Kristin Siggeirsdottir, Eleanor M Simonsick, Elisabeth Sornay-Rendu, Reijo Sund, Karin M A Swart, Pawel Szulc, Junko Tamaki, David J Torgerson, Natasja M van Schoor, Tjeerd P van Staa, Joan Vila, Nicholas J Wareham, Nicole C Wright, Noriko Yoshimura, M Carola Zillikens, Marta Zwart, Liesbeth Vandenput, Mattias Lorentzon, William D Leslie, John A Kanis","doi":"10.1093/jbmr/zjaf091","DOIUrl":"10.1093/jbmr/zjaf091","url":null,"abstract":"<p><p>The aim of this international meta-analysis was to quantify the predictive value of BMI for incident fracture and relationship of this risk with age, sex, follow-up time, and BMD. A total of 1 667 922 men and women from 32 countries (63 cohorts), followed for a total of 16.0 million person-years were studied. 293 325 had FN BMD measured (2.2 million person-years follow-up). An extended Poisson model in each cohort was used to investigate relationships between WHO-defined BMI categories (Underweight: <18.5 kg/m2; Normal: 18.5-24.9 kg/m2; Overweight: 25.0-29.9 kg/m2; Obese I: 30.0-34.9 kg/m2; Obese II: ≥35.0 kg/m2) and risk of incident osteoporotic, major osteoporotic and hip fracture (HF). Inverse-variance weighted β-coefficients were used to merge the cohort-specific results. For the subset with BMD available, in models adjusted for age and follow-up time, the hazard ratio (95% CI) for HF comparing underweight with normal weight was 2.35 (2.10-2.60) in women and for men was 2.45 (1.90-3.17). Hip fracture risk was lower in overweight and obese categories compared to normal weight [obese II vs normal: women 0.66 (0.55-0.80); men 0.91 (0.66-1.26)]. Further adjustment for FN BMD T-score attenuated the increased risk associated with underweight [underweight vs normal: women 1.69 (1.47-1.96); men 1.46 (1.00-2.13)]. In these models, the protective effects of overweight and obesity were attenuated, and in both sexes, the direction of association reversed to higher fracture risk in Obese II category [Obese II vs Normal: women 1.24 (0.97-1.58); men 1.70 (1.06-2.75)]. Results were similar for other fracture outcomes. Underweight is a risk factor for fracture in both men and women regardless of adjustment for BMD. However, while overweight/obesity appeared protective in base models, they became risk factors after additional adjustment for FN BMD, particularly in the Obese II category. This effect in the highest BMI categories was of greater magnitude in men than women. These results will inform the second iteration of FRAX®.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1144-1155"},"PeriodicalIF":5.9,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative single-cell RNA-seq and ATAC-seq identifies transcriptional and epigenetic blueprint guiding osteoclastogenic trajectory.","authors":"Amitabh Das, Keita Saeki, Stefania Dell'Orso, Xiaobei Wang, Kim C Mansky, Joseph Stains, Keiko Ozato, Hong-Wen Deng, Vivek Thumbigere-Math","doi":"10.1093/jbmr/zjaf084","DOIUrl":"10.1093/jbmr/zjaf084","url":null,"abstract":"<p><p>Osteoclasts (OCs) are multinucleated bone resorbing cells essential for skeletal development and remodeling. In adulthood, OCs originate from the serial fusion of monocytes, yet the transcriptional and epigenetic mechanisms shaping their osteoclastogenic potential at a single-cell resolution remain poorly understood. Here, we present an integrative multi-omics analysis, combining single-cell (sc) RNA-seq, scATAC-seq, bulk RNA-seq, and Chromatin Immunoprecipitation (ChIP)-seq, to comprehensively define the regulatory landscape of osteoclastogenesis in WT and interferon regulatory factor 8 (IRF8) conditional KO mice. We uncovered a highly structured and sequential differentiation trajectory from hematopoietic stem and progenitor cells to common monocyte progenitors (cMoPs) to mature monocytes, with each stage exhibiting distinct transcriptional and epigenetic signatures. cMoPs and monocytes are the critical stages when OC lineage priming occurs, characterized by transcriptional and epigenetic activation of cytoskeletal, immune, and cell migration pathways. This priming is tightly regulated to prevent premature OC differentiation and IRF8 acts as a negative regulator of osteoclastogenesis by maintaining monocyte identity and restricting chromatin accessibility at osteoclastogenic loci. IRF8 deficiency disrupts this balance, leading to chromatin reprogramming characterized by increased accessibility at OC-promoting loci (Nfatc1, Cebpe) and reduced accessibility at monocyte-specific genes (Mafb, Klf4), thereby priming precursors towards pre-mature osteoclastogenesis. Just as NFATc1 is recognized as a master activator of osteoclastogenesis, our findings position IRF8 as a master negative regulator of osteoclastogenesis, maintaining the delicate balance required for proper bone homeostasis. Collectively, this study provides unprecedented resolution into the molecular mechanisms shaping OC precursor identity and offers novel insights into potential therapeutic targets for osteolytic disorders.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1127-1143"},"PeriodicalIF":5.9,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144511273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative single-cell multi-omics analysis captures a role of IRF8 as a gatekeeper for osteoclastogenesis.","authors":"Yuuki Imai","doi":"10.1093/jbmr/zjaf103","DOIUrl":"10.1093/jbmr/zjaf103","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1104-1105"},"PeriodicalIF":5.9,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights into bone mineral density for predicting hip fracture.","authors":"Tony M Keaveny","doi":"10.1093/jbmr/zjaf101","DOIUrl":"10.1093/jbmr/zjaf101","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1101-1103"},"PeriodicalIF":5.9,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Femoral neck width is associated with unique trajectories of age-related hip structural changes and fracture risk within populations of adult women and men.","authors":"Karl J Jepsen, Todd L Bredbenner, Carrie A Karvonen-Gutierrez, Aleda M Leis, Michelle M Hood, Siobán D Harlow, John Randolph, Gregory A Clines, Steffenie Merillat, Michael R Elliott, Jane A Cauley, Gail A Greendale, Arun S Karlamangla, Katherine W Peters, Stephanie L Harrison, Li-Yung Lui, Peggy M Cawthon, Eric Orwoll","doi":"10.1093/jbmr/zjaf090","DOIUrl":"10.1093/jbmr/zjaf090","url":null,"abstract":"<p><p>Osteoporosis management relies heavily on areal BMD (aBMD) to identify women and men with reduced bone strength. We tested the hypothesis that baseline FN external size is associated with different bone-loss and area-gain trajectories that are not reflected in aBMD-decline but have different biomechanical implications. We analyzed data from 4 longitudinal studies with repeated hip DXA scans of women and men over 10-15 yr of follow-up. Changes in FN BMC, area, and aBMD were compared across height-adjusted baseline FN area tertiles using linear models. Fracture risk differences across the tertiles were tested using Cox proportional-hazard models. Women and men with smaller baseline FN area had smaller BMC-declines and greater area-increases over 10-15 yr. In contrast, those with a larger FN area experienced twice the annual BMC-declines but much smaller area-increases. In general, these structural changes were not reflected in aBMD-changes for either sex. The likelihood of fracturing a hip was 2.5 times greater for women and 2.4-4.2 times greater for men in the larger FN area tertile compared to those in the smaller FN area tertile. Unique patterns of age-related structural changes with different biomechanical implications were identified within populations of women and men. These results challenge the general assumption that age-related structural changes are homogenous within a population and question whether aBMD-declines reflect strength-declines consistently among women and men. How these unique patterns of structural change affect the response of women and men to osteoporosis interventions remains to be determined.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1114-1126"},"PeriodicalIF":5.9,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12487784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}