Journal of Bone and Mineral Research最新文献

{"title":"Probability of achieving bone mineral density treatment targets with abaloparatide and teriparatide.","authors":"Felicia Cosman, Bruce H Mitlak, Yamei Wang, Leny Pearman, Carolina A Moreira, E Michael Lewiecki, Steven R Cummings","doi":"10.1093/jbmr/zjaf053","DOIUrl":"10.1093/jbmr/zjaf053","url":null,"abstract":"<p><p>The goal of treatment for women at high risk of fracture who have a T-score ≤-2.5 is to mitigate fracture risk by achieving T-scores at least above -2.5. In the ACTIVE trial, 2463 women with osteoporosis aged 49-86 yr were treated for 18 mo with abaloparatide (80 μg), teriparatide (20 μg), or placebo. In ACTIVExtend, eligible women from the abaloparatide and placebo groups received weekly treatment with 70 mg of alendronate for 2 additional years. This post hoc analysis of ACTIVE and ACTIVExtend included women with baseline TH or LS T-scores ≤-2.5. Logistic regression was used to predict the probability of achieving a T-score >-2.5 at the TH or LS during 18 mo of treatment with abaloparatide or teriparatide and during 3.5 yr with the sequence of abaloparatide/alendronate compared to placebo/alendronate. At baseline, 23% and 74% of women enrolled in ACTIVE had T-scores ≤-2.5 at the TH and LS, respectively. Over 18 mo of treatment, more than 50% of women were likely to achieve TH T-scores >-2.5, with baseline TH T-scores as low as -2.7 for both abaloparatide and teriparatide. More than 50% of women were predicted to achieve an LS T-score >-2.5 with a baseline LS T-score as low as -3.3 for abaloparatide or -3.2 on teriparatide. Over 3.5 yr of sequential treatment with abaloparatide/alendronate, >50% of women with baseline TH T-scores ≥-2.9 and LS T-scores ≥-3.5 were predicted to achieve T-scores >-2.5, respectively. A patient's BMD at baseline and the probability of achieving target T-scores with treatment should be considered when determining that treatment should be initiated in patients at high or very high risk of fracture.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"773-778"},"PeriodicalIF":5.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954761","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":"Macrophages: the maestros of bone repair mechanobiology.","authors":"Georgios Kotsaris, Joel D Boerckel","doi":"10.1093/jbmr/zjaf024","DOIUrl":"10.1093/jbmr/zjaf024","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"721-722"},"PeriodicalIF":5.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956877","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":"Methyltransferase 1-mediated tRNA N7-methylguanosine modification regulates dentin formation during tooth root development via p53 signaling.","authors":"Xinyan Gan, Kun He, Qiuchan Xiong, Rui Sheng, Kexin Lei, Shuang Jiang, Xiaoyu Yang, Yimeng Cai, Denghao Huang, Yu Shi, Ling Ye, Quan Yuan, Qiwen Li","doi":"10.1093/jbmr/zjaf056","DOIUrl":"10.1093/jbmr/zjaf056","url":null,"abstract":"<p><p>tRNA N7-methylguanosine (m7G) is one of the most abundant epigenetic modifications in mammals, which is catalyzed by the methyltransferase 1-WD repeat-containing protein 4 (METTL1-WDR4) complex. Missense mutations in WDR4 have been linked to primordial dwarfism, which shows severe craniofacial developmental deformities including small teeth, but the underlying molecular mechanisms remain elusive. In this study, we explore the effect of m7G modification on dentin formation during tooth root development. METTL1 was actively expressed in mice developing tooth roots, and its expression became undetectable after tooth root formation. Next, we generated Prrx1-Cre driven Mettl1 (Prrx1Cre;Mettl1fl/fl) conditional KO mice to delete Mettl1 in dental mesenchyme and explored its regulation during tooth development. Micro-computed tomography revealed that the roots of the mandibular first molar in Prrx1Cre;Mettl1fl/fl mice were shorter and smaller compared to littermate control, with a reduction in the width of dentin and pre-dentin in both the root area and the crown area. Wdr4R215L/R215L mice also exhibited tooth root shortening and dentin thinning, phenocopying the Prrx1Cre;Mettl1fl/fl mice. Moreover, METTL1-depleted human dental pulp cells (hDPCs) showed decreased ability of proliferation, migration, and odontogenic differentiation. RNA-seq revealed upregulation of the p53 signaling pathway and cell cycle arrest after deletion of Mettl1. The proliferation and odontogenic differentiation of METTL1-depleted hDPCs is partially rescued with pifithrin-α (PFT-α), a p53 signaling inhibitor. Taken together, our results demonstrate that loss of METTL1-mediated tRNA m7G modification impairs the proliferation and odontogenic differentiation of hDPCs via the p53 signaling pathway and affects the dentin formation during tooth root development, providing a novel epigenetic mechanism underlying small teeth.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"813-823"},"PeriodicalIF":5.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964167","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":"Time-lapse high-resolution peripheral quantitative computed tomography for chronic kidney disease bone monitoring: a step toward reducing bone biopsies?","authors":"Felix N von Brackel","doi":"10.1093/jbmr/zjaf052","DOIUrl":"10.1093/jbmr/zjaf052","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"723-724"},"PeriodicalIF":5.1,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957317","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":"A high-quality diet remains the best nutritional strategy to prevent fracture.","authors":"Jeri W Nieves, Sue A Shapses","doi":"10.1093/jbmr/zjaf048","DOIUrl":"10.1093/jbmr/zjaf048","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"565-566"},"PeriodicalIF":5.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762495","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":"Effects of cocoa extract supplementation and multivitamin/multimineral supplements on self-reported fractures in the Cocoa Supplement and Multivitamins Outcomes Study randomized clinical trial.","authors":"Carolyn J Crandall, Sharon Chou, Eunjung Kim, Dana Ratnarajah, Nancy R Cook, Allison Clar, Howard D Sesso, JoAnn E Manson, Meryl S LeBoff","doi":"10.1093/jbmr/zjaf030","DOIUrl":"10.1093/jbmr/zjaf030","url":null,"abstract":"<p><p>Osteoporosis is a major public health problem among older adults. Forty percent of older US adults take multivitamin/multimineral (MVM) supplementation. The effects of MVM supplementation on fractures are unclear. Preclinical and observational studies suggest that MVM and flavanols may have beneficial effects on bone. We conducted an ancillary study to Cocoa Supplement and Multivitamin Outcomes Study (COSMOS; NCT05232669) designed to investigate incident fracture and injurious falls in 21 442 COSMOS participants (12 666 females aged ≥65 yr and 8776 males aged ≥60 yr) randomized in a 2 × 2 factorial design to 1 of 4 intervention groups: cocoa extract + MVM, cocoa extract + MVM placebo, cocoa extract placebo + MVM, or double placebo. The daily cocoa extract supplement contained 500 mg/d flavanols and 80 mg/d (-)-epicatechin (Mars Edge); the daily MVM supplement was Centrum Silver (Haleon). The median (interquartile range) duration of the intervention was 3.6 (3.2-4.2) yr. Annually, participants self-reported incident fractures. In intention-to-treat analyses, we examined the effects of cocoa extract and MVM on the primary outcomes of total clinical fracture (hip, upper leg, forearm/wrist, pelvis, upper arm/shoulder, spine, knee, or other), hip fracture, and nonvertebral fracture, and secondary outcomes of clinical spine, forearm/wrist, major osteoporotic, and pelvic fracture using Cox proportional hazards models. During the intervention period, 2083 incident clinical fractures occurred. Compared with placebo, cocoa extract was not significantly associated with lower risk of incident clinical fracture (adjusted hazard ratio [aHR] 1.03, 95% CI 0.95-1.12) or nonvertebral fracture (aHR 1.05, 95% CI 0.96-1.14). MVM supplementation was not associated with lower risk of total clinical fracture (aHR 1.09, 95% CI 1.00-1.19), hip fracture (aHR 1.06, 95% CI 0.80-1.42), or nonvertebral fracture (aHR 1.10, 95% CI 1.00-1.20). These findings do not support the use of cocoa extract or MVM to decrease fracture risk in older individuals not selected for pre-existing osteoporosis.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"591-602"},"PeriodicalIF":5.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439722","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":"Vitamin D and disease prevention in 2024: commentary on recent Endocrine Society recommendations.","authors":"Catherine M Gordon, Meryl S LeBoff","doi":"10.1093/jbmr/zjaf036","DOIUrl":"10.1093/jbmr/zjaf036","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"569-571"},"PeriodicalIF":5.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565712","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":"Brittle, but not boring: a fresh look at osteogenesis imperfecta type V.","authors":"Mathieu Ferron, Jean Vacher","doi":"10.1093/jbmr/zjaf035","DOIUrl":"10.1093/jbmr/zjaf035","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"563-564"},"PeriodicalIF":5.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603168","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":"Circulating CD34-positive cells are associated with prolonged time to fracture in people with Duchenne muscular dystrophy on chronic glucocorticoids.","authors":"Angela Sadlowski, Julia See, Sonum Bharill, Weixin Zhang, Arryn Otte, Emely Loscalzo, Nazanin Yousefzadeh, Ethan Gough, Tricia Nilles, Sisir Barik, Malinda Wu, Janet L Crane","doi":"10.1093/jbmr/zjaf041","DOIUrl":"10.1093/jbmr/zjaf041","url":null,"abstract":"<p><p>Glucocorticoids decrease preosteoclast (POC) platelet-derived-growth-factor-type-BB (PDGF-BB), reducing migration of endothelial and osteo-progenitor cells, impairing skeletal angiogenesis and osteogenesis in mice. To explore human translation, we conducted a case-control study on Duchenne muscular dystrophy (DMD) youth treated with chronic glucocorticoids (n=24) relative to healthy controls (n=13) to explore the association of PDGF-BB, VEGF, angiogenin concentration and peripheral blood mononuclear cell (PBMC) subpopulations as surrogates of POCs (CD14+/Stro-1-/CD105-), skeletal progenitor cells (SPCs: Stro-1+/CD105+/CD14-/CD45-), and endothelial/hematopoietic progenitor cells (CD34+/CD14-/Stro-1-/CD105-) and CE140b mean fluorescence intensity (MFI) to fracture. People with DMD (8-20 years), were stratified by prior and subsequent fractures relative to biospecimen collection. Healthy controls were age- and sex-matched. Differences between groups were assessed with one-way ANOVA with post-hoc Tukey's test, retrospective fractures by Kendall Tau correlation, and prospective fractures by bivariable and multivariable accelerated time failure models. Baseline characteristics between groups were similar, though people with DMD were shorter relative to healthy controls, and in the DMD groups, those with prior fractures had a longer duration of glucocorticoid therapy. We noted decreased PDGF-BB concentration and percentages of circulating POCs, SPCs, and CD34+ cells in people with DMD relative to healthy controls. Circulating CD34+ cell percentage positively correlated with PDGF-BB concentration, similar to murine models. Lower percentage of circulating SPCs and CD140b MFI was associated with increased number of retrospective fractures. After a mean follow-up of 2.23 yr, 79% of people with DMD sustained a subsequent fracture. Higher PDGF-BB concentration and percent of POC, SPCs, and CD34+ cells were associated with a longer time to next fracture. After controlling for covariates of fracture risk, increased percentage of CD34+ cells continued to be associated with prolonged time to fracture. Circulating CD34+ cells may thus be a potential biomarker to predict acute fracture risk in young people with DMD on chronic glucocorticoids.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"617-627"},"PeriodicalIF":5.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12103721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623042","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":"KDM6B preferentially promotes bone formation over resorption to facilitate postnatal bone mass accrual through collagen triple helix repeat containing 1-mediated PKCδ/MAPKs signaling.","authors":"Qian Liu, Ying Gan, Xingli Hu, Wei Liu, Xiaoxia Liao, Jingyun Zhang, Xiaoxia Li, Jie Zhou, Baoli Wang","doi":"10.1093/jbmr/zjaf028","DOIUrl":"10.1093/jbmr/zjaf028","url":null,"abstract":"<p><p>Lysine demethylase 6B (KDM6B) plays a role in regulating osteoblast differentiation and fetal bone ossification. Nevertheless, its involvement in regulating postnatal bone homeostasis and bone mass accrual remains unclear. In this study, we generated mice lacking Kdm6b gene specifically in mesenchyme and osteoprogenitor cells using a conditional strategy. The adult mice of both mutant strains had decreased cancellous bone mass. The absence of Kdm6b in mesenchyme led to decreased numbers of osteoblasts and osteoclasts, increased marrow adipocytes, as well as repressed bone formation and resorption. Additionally, Kdm6b-deficient bone marrow stromal cells (BMSCs) displayed impaired osteogenic differentiation and exerted an inhibitory effect on osteoclastogenesis. RNA-seq combined with gene expression analysis uncovered downregulation of collagen triple helix repeat containing 1 (CTHRC1) and a lower RANKL/osteoprotegerin (OPG) ratio in BMSCs of the mutant mice. Further mechanistic explorations demonstrated that KDM6B epigenetically upregulated CTHRC1 expression by removing the repressive H3K27me3 mark from its promoter, thereby triggering PKCδ/MAPKs signaling to facilitate osteoblast differentiation. CTHRC1 was able to mitigate the dysregulated osteogenic and adipogenic differentiation induced by Kdm6b deficiency. This study provides evidence that KDM6B regulates postnatal bone homeostasis through balancing osteoblast and osteoclast differentiation. Given its predominant promotion of osteoblastic bone formation over osteoclastic bone resorption, KDM6B tends to promote postnatal bone mass accrual.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"671-687"},"PeriodicalIF":5.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439784","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}