Journal of Bone and Mineral Research最新文献

{"title":"Defining the key clinician skills and attributes for competency managing patients with osteoporosis and fragility fractures.","authors":"Kirtan Ganda, Michael Bennett, Jacqueline Centre, Robin M Daly, Markus J Seibel, Jason Talevski, Tania Winzenberg","doi":"10.1093/jbmr/zjae146","DOIUrl":"https://doi.org/10.1093/jbmr/zjae146","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142277664","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":"Independent contribution of gonads and sex chromosomes to sex differences in bone mass and strength in the four-Core genotypes mouse model.","authors":"Gabriel Ramirez,Chiebuka Okpara,Matthew Arnett,Dyann M Segvich,Padmini Deosthale,Paola Ortiz González,Alexander E Kritikos,Julian Balanta Melo,Natasha Sanz,Fabrizio Pin,Joseph M Wallace,Lilian I Plotkin","doi":"10.1093/jbmr/zjae147","DOIUrl":"https://doi.org/10.1093/jbmr/zjae147","url":null,"abstract":"Vertebrate sexual dimorphism is ascribed to the presence of testes or ovaries, and, hence, to the secretion of gonad-specific hormones. However, mounting evidence indicates that sex differences in tissues and organs also stem from the presence of sex chromosomes (XX or XY). To tease out the contribution of gonads from sex chromosomes to the musculoskeletal system, we used the Four-Core Genotypes (FCG) mouse model, in which the Sry gene, which dictates testis formation, was either deleted in the Y chromosome, resulting in XY mice with ovaries (XY-SryO), or overexpressed in XX mice, resulting in XX mice with testes (XXT), together with gonadal males XY-SryT (Sry deletion and overexpression of the Sry transgene in chromosome 3) and females XXO. The FCG mice are generated by crossing XXO with XY-SryT mice, all of C57BL/6 J background. We now show that the musculoskeletal phenotype of 2- to 4-month-old FCG mice varies based on both gonads and sex chromosomes, depending on the age and the organ/tissue/cell analyzed. The effect of sex chromosomes on body weight, fat and lean/skeletal muscle mass, and bone mass and structure is minor in 2-/3-month-old mice, soon after sexual maturation. The contribution of sex chromosomes (XX versus XY-Sry in mice with the same gonads and sex hormones) in several of our measurements becomes apparent in adult 4-month-old mice. Contribution of 1X and 1Y-Sry versus 2X chromosomes varies among different measurements in gonadal males or females, and mice with XY-Sry chromosomes might have higher or lower values that XX mice. Our study shows XX versus XY-Sry chromosome contribution to the musculoskeletal phenotype, which becomes more evident as the animals reach peak bone mass, suggesting that while gonadal sex has a major role, sex chromosomes are a so far unrecognized contributor to musculoskeletal mass and bone strength.","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":"161 1","pages":""},"PeriodicalIF":6.2,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142215702","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":"Weight change, variability, and trajectories and risk of hip fracture among older adults with Dysglycemia: the cardiovascular health study.","authors":"Shohinee Sarma, Petra Bůžková, Rachel E Elam, Howard A Fink, Jane A Cauley, Luc Djoussé, Joshua Barzilay, Kenneth J Mukamal","doi":"10.1093/jbmr/zjae142","DOIUrl":"https://doi.org/10.1093/jbmr/zjae142","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes mellitus and lower weight are both associated with osteoporotic fractures, but the roles of variability and trajectory are less clear.1 The associations of these factors among older adults with dysglycemia, who are at highest risk of fracture, with fracture risk and bone mineral density (BMD) remains uncertain.</p><p><strong>Methods: </strong>We followed 775 men and 1080 women from the Cardiovascular Health Study (mean age 77.4 years) with abnormal oral glucose tolerance testing in 1989-1990. We measured their weights yearly through 1994-1995 and derived intra-individual mean weight, weight slope, and weight variability. We also used growth mixture modelling to derive four latent body-mass index trajectories over time. We used Cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence intervals (CI) for subsequent hip fracture through 2015 and linear regression models to estimate cross-sectional associations with bone mineral density (BMD) of the hip.</p><p><strong>Results: </strong>Each 10 kg higher mean weight was associated with a lower risk of subsequent hip fracture overall (HR 0.81; CI 0.70-0.94) and among women (HR 0.76; CI 0.64-0.91) and with higher BMD (P-value <0.001). Higher weight variability was directly associated with incident hip fracture among women (HR 1.18; CI: 1.03-1.35). Compared with a stable trajectory, a \"progressive overweight\" trajectory was associated with lower risk of hip fracture (HR 0.66; CI: 0.44-0.99). An uncommon trajectory of \"accelerating obesity\" was associated with higher BMD.</p><p><strong>Conclusions: </strong>Among older adults with dysglycemia at high risk for fracture, lower mean weight is associated with higher fracture risk, but variability and trajectory may also contribute. These results highlight the complex effects of weight in older age.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131393","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":"The multifaceted roles of mitochondria in osteoblasts: from energy production to mitochondrial-derived vesicle secretion.","authors":"Joonho Suh, Yun-Sil Lee","doi":"10.1093/jbmr/zjae088","DOIUrl":"10.1093/jbmr/zjae088","url":null,"abstract":"<p><p>Mitochondria in osteoblasts have been demonstrated to play multiple crucial functions in bone formation from intracellular adenosine triphosphate production to extracellular secretion of mitochondrial components. The present review explores the current knowledge about mitochondrial biology in osteoblasts, including mitochondrial biogenesis, bioenergetics, oxidative stress generation, and dynamic changes in morphology. Special attention is given to recent findings, including mitochondrial donut formation in osteoblasts, which actively generates mitochondrial-derived vesicles (MDVs), followed by extracellular secretion of small mitochondria and MDVs. We also discuss the therapeutic effects of targeting osteoblast mitochondria, highlighting their potential applications in improving bone health.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1205-1214"},"PeriodicalIF":5.1,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141440070","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":"High physical activity is associated with greater cortical bone size, better physical function, and with lower risk of incident fractures independently of clinical risk factors in older women from the SUPERB study.","authors":"Lisa Johansson, Henrik Litsne, Kristian F Axelsson, Mattias Lorentzon","doi":"10.1093/jbmr/zjae114","DOIUrl":"10.1093/jbmr/zjae114","url":null,"abstract":"<p><p>The Physical Activity Scale for the Elderly (PASE) is a validated test to assess physical activity in older people. It has not been investigated if physical activity, according to PASE, is associated with fracture risk independently from the clinical risk factors (CRFs) in FRAX, bone mineral density (BMD), comorbidity, and if such an association is due to differences in physical performance or bone parameters. The purpose of this study was to evaluate if PASE score is associated with bone characteristics, physical function, and independently predicts incident fracture in 3014 75-80-yr-old women from the population-based cross-sectional SUPERB study. At baseline, participants answered questionnaires and underwent physical function tests, detailed bone phenotyping with DXA, and high-resolution peripheral quantitative CT. Incident fractures were X-ray verified. Cox regression models were used to assess the association between PASE score and incident fractures, with adjustments for CRFs, femoral neck (FN) BMD, and Charlson comorbidity index. Women were divided into quartiles according to PASE score. Quartile differences in bone parameters (1.56% for cortical volumetric BMD and 4.08% for cortical area, Q4 vs Q1, p = .007 and p = .022, respectively) were smaller than quartile differences in physical performance (27% shorter timed up and go test, 52% longer one leg standing time, Q4 vs Q1). During 8 yr (median, range 0.20-9.9) of follow-up, 1077 women had any fracture, 806 a major osteoporotic fracture (MOF; spine, hip, forearm, humerus), and 236 a hip fracture. Women in Q4 vs. Q1 had 30% lower risk of any fracture, 32% lower risk of MOF, and 54% lower risk of hip fracture. These associations remained in fully adjusted models. In conclusion, high physical activity was associated with substantially better physical function and a lower risk of any fracture, MOF and hip fracture, independently of risk factors used in FRAX, FN BMD, and comorbidity.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1284-1295"},"PeriodicalIF":5.1,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141597973","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":"Letter to the editor regarding \"The American Society for Bone and Mineral Research Task Force on clinical algorithms for fracture risk report\".","authors":"Bess Dawson-Hughes, Felicia Cosman, Michael McClung","doi":"10.1093/jbmr/zjae107","DOIUrl":"10.1093/jbmr/zjae107","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1371-1372"},"PeriodicalIF":5.1,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747042","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":"Romosozumab followed by denosumab versus denosumab only: a post hoc analysis of FRAME and FRAME extension.","authors":"Felicia Cosman, Mary Oates, Donald Betah, Jen Timoshanko, Zhenxun Wang, Serge Ferrari, Michael R McClung","doi":"10.1093/jbmr/zjae116","DOIUrl":"10.1093/jbmr/zjae116","url":null,"abstract":"<p><p>Osteoanabolic-first treatment sequences are superior to oral bisphosphonates for fracture reduction and bone mineral density (BMD) gain. However, data comparing osteoanabolic medications, with the more potent antiresorptive, denosumab (DMAb), are limited. We analyzed FRAME and FRAME Extension data to assess BMD and fracture incidence in patients treated with romosozumab (Romo) followed by DMAb (Romo/DMAb) versus DMAb (DMAb/DMAb) for 24 months. In FRAME, women aged ≥55 years (total hip [TH] or femoral neck [FN] T-score: -2.5 to -3.5) were randomized to Romo or placebo for 12 months followed by DMAb for 12 months. In FRAME Extension, both cohorts received DMAb for another 12 months. This post hoc analysis compared BMD change and fracture incidence in patients on Romo/DMAb (months 0-24) versus DMAb/DMAb (months 12-36). Patient characteristics were balanced by propensity score weighting (PSW) and sensitivity analyses were conducted using PSW with multiple imputation (PSW-MI) and propensity score matching (PSM). Unmeasured confounding was addressed using E-values. After PSW, over 24 months, compared with DMAb/DMAb, treatment with Romo/DMAb produced significantly greater BMD increases at the lumbar spine [LS], TH, and FN (mean differences: 9.3%, 4.4%, and 4.1%, respectively; all p<0.001). At month 24, in women with a baseline T-score of -3.0, the probability of achieving a T-score > -2.5 was higher with Romo/DMAb versus DMAb/DMAb (LS: 92% versus 47%; TH: 50% versus 5%). In the Romo/DMAb versus DMAb/DMAb cohorts, new vertebral fractures were significantly reduced (0.62% versus 1.26% [odds ratio = 0.45; p=0.003]) and rates of clinical, nonvertebral, and hip fractures were lower (differences not significant). Similar BMD and fracture outcomes were observed with PSW-MI and PSM sensitivity analyses. The sequence of Romo/DMAb resulted in greater BMD gains and higher probability of achieving T-scores > -2.5, significantly reduced new vertebral fracture incidence, and numerically lowered the incidence (not significant) of clinical, nonvertebral, and hip fractures versus DMAb only through 24 months.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1268-1277"},"PeriodicalIF":5.1,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747043","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":"One-carbon metabolism supports S-adenosylmethionine and m6A methylation to control the osteogenesis of bone marrow stem cells and bone formation.","authors":"Wenjie Zhang, Yujia Bai, Lili Hao, Yiqing Zhao, Lujin Zhang, Wenqian Ding, Yipin Qi, Qiong Xu","doi":"10.1093/jbmr/zjae121","DOIUrl":"10.1093/jbmr/zjae121","url":null,"abstract":"<p><p>The skeleton is a metabolically active organ undergoing continuous remodeling initiated by bone marrow stem cells (BMSCs). Recent research has demonstrated that BMSCs adapt the metabolic pathways to drive the osteogenic differentiation and bone formation, but the mechanism involved remains largely elusive. Here, using a comprehensive targeted metabolome and transcriptome profiling, we revealed that one-carbon metabolism was promoted following osteogenic induction of BMSCs. Methotrexate (MTX), an inhibitor of one-carbon metabolism that blocks S-adenosylmethionine (SAM) generation, led to decreased N6-methyladenosine (m6A) methylation level and inhibited osteogenic capacity. Increasing intracellular SAM generation through betaine addition rescued the suppressed m6A content and osteogenesis in MTX-treated cells. Using S-adenosylhomocysteine (SAH) to inhibit the m6A level, the osteogenic activity of BMSCs was consequently impeded. We also demonstrated that the pro-osteogenic effect of m6A methylation mediated by one-carbon metabolism could be attributed to HIF-1α and glycolysis pathway. This was supported by the findings that dimethyloxalyl glycine rescued the osteogenic potential in MTX-treated and SAH-treated cells by upregulating HIF-1α and key glycolytic enzymes expression. Importantly, betaine supplementation attenuated MTX-induced m6A methylation decrease and bone loss via promoting the abundance of SAM in rat. Collectively, these results revealed that one-carbon metabolite SAM was a potential promoter in BMSC osteogenesis via the augmentation of m6A methylation, and the cross talk between metabolic reprogramming, epigenetic modification, and transcriptional regulation of BMSCs might provide strategies for bone regeneration.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1356-1370"},"PeriodicalIF":5.1,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141910933","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":"Longitudinal Changes in Bone Mineral Density in Adults with Cystic Fibrosis.","authors":"Reem Jad, Xiayi Ma, Sanja Stanojevic, Abarnaa Illango, Elizabeth Tullis, Julie Gilmour, Christopher H Goss, Lisa J Strug, Anne L Stephenson","doi":"10.1093/jbmr/zjae139","DOIUrl":"10.1093/jbmr/zjae139","url":null,"abstract":"<p><strong>Background: </strong>Improved survival in people with cystic fibrosis (pwCF) presents new complexities of care, including CF-related bone disease, a common complication in older pwCF. The trajectory of bone loss with age in this population remains unclear. The objective of this study was to estimate the average rate of change in bone mineral density (BMD) in adults with CF.</p><p><strong>Methods: </strong>This retrospective study included adults with CF, aged 25-48 years, followed between January 2000 and December 2021. Subjects with at least one dual-energy X-ray absorptiometry (DXA) scan were included. Scans obtained post-transplantation, after the initiation of bisphosphonates or cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy were excluded. The primary outcome was BMD (g/cm2) at the lumbar spine (LS) and femoral neck (FN). A linear mixed-effects model with both random intercept and random slope terms was used to estimate the average annual change in BMD.</p><p><strong>Results: </strong>A total of 1502 DXA scans in 500 adults (average age 28.4y) were included. There was a statistically significant annual decline in BMD of -0.008 gm/cm2/year (95% CI -0.009, -0.007) at the FN and -0.006 gm/cm2/year (95% CI -0.007, -0.004) at the LS. Relative to BMD at age 25, there was a -18.8% decline at the FN by age 48 years and a -11% decline at the LS. Pancreatic insufficient (PI) subjects had a faster rate of decline in BMD compared to pancreatic sufficient (PS) subjects. After adjusting for markers of disease severity, the annual rate of decline remained significant.</p><p><strong>Conclusions: </strong>Individuals with CF experience bone loss at an age when it is not anticipated, thereby entering early adulthood, where further bone loss is inevitable especially with the decrease in estrogen during menopause, with suboptimal BMD. As the CF population ages, it will become very important to consider interventions to maximize bone health.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102673","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":"Femoral neck width and hip fracture risk.","authors":"Jacqueline R Center, John A Eisman","doi":"10.1093/jbmr/zjae113","DOIUrl":"10.1093/jbmr/zjae113","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1201-1202"},"PeriodicalIF":5.1,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141578436","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}