Bone最新文献

{"title":"Exosomal miR-133b-3p modulates TGF-β1/Treg immunomodulation to ameliorate osteoporosis","authors":"Yun Zhao , Xingyao Yang , Jialun Wang , Fangdong Chen , Guojia Shi , Jun Cheng , Shuxing Xing , Xiao Liu","doi":"10.1016/j.bone.2025.117658","DOIUrl":"10.1016/j.bone.2025.117658","url":null,"abstract":"<div><h3>Purpose</h3><div>Osteoporosis (OP) is influenced by dysregulated miRNAs, particularly during osteoblast differentiation. The precise mechanisms are still under debate. This study aimed to explore the impact of bone marrow mesenchymal stem cells (BMSCs)-derived exosomal miR-133b-3p on the TGF-β1/Treg-mediated immune pathway, offering insights into OP's pathogenesis and potential therapeutic targets.</div></div><div><h3>Materials and methods</h3><div>Bioinformatics analysis of GEO dataset (<span><span>GSE64433</span><svg><path></path></svg></span>) identified differentially expressed miRNAs in osteoporosis. Target genes were predicted using TargetScan, miRDB, miRTarBase, and miRWalk databases, followed by GO and KEGG pathway enrichment analyses. An OP rat model was constructed by ovariectomy (<em>n</em> = 36, randomly allocated into three groups: control, OP, and OP+exosomal <em>miR-133b-3p</em>, <em>n</em> = 12 per group). BMSCs were isolated at 12 weeks post-OVX.Flow cytometry was used to identify the surface markers of BMSCs, <em>CD29, CD44, CD106, CD34,</em> and <em>CD45</em>. Exosomes were isolated from passages 3–5 BMSCs using ExoQuick kit. Transmission electron microscopy and nanoparticle tracking analysis were used to observe the morphology and size distribution of exosomes, and the expression of exosomal protein markers <em>CD9, CD63,</em> and <em>TSG101</em> was detected by Western blot. qRT-PCR was performed to detect <em>miR-133b-3p</em> and <em>TGF-β1</em> expression in exosomes. Dual-luciferase reporter assay validated the direct interaction between <em>miR-133b-3p</em> and <em>TGF-β1</em> 3’-UTR. Dual-energy X-ray bone densitometry was used to detect bone mineral density (BMD) after 4 weeks of treatment with <em>miR-133b-3p</em>-enriched exosomes (200 μg weekly via tail vein injection). Micro-CT was used to analyze the BV/TV, Tb.N, Tb.Th, SMI, Ct.Th, BA/TA, and Tb.Sp. In vitro experiments using isolated CD4+ T cells were conducted to assess <em>TGF-β1</em> expression and <em>CD4</em> <em>+</em> <em>CD25</em> <em>+</em> <em>Foxp3+</em> Treg cell differentiation via Western blot, RT-PCR, and flow cytometry. Osteoclast marker enzymes <em>TRAP, MMP-9,</em> and <em>Cathepsin K</em> were identified using immunohistochemistry.</div></div><div><h3>Results</h3><div>Bioinformatics analysis revealed 27 differentially expressed miRNAs. Target prediction of <em>miR-133b-3p</em> identified 44 high-confidence genes, with <em>TGF-β1</em> emerging as a key target. BMSCs expressing <em>CD29, CD44,</em> and CD106 (but not CD34 and CD45) were isolated from both control and OP rats. The identified exosomes were roughly spherical with a double-layered membrane, they had a size distribution of about 103.5 ± 8.2 nm and 105.8 ± 10.6 nm, respectively, and had a positive expression of <em>CD9 CD63,</em> and <em>TSG101</em>. qRT-PCR analysis revealed significantly decreased <em>miR-133b-3p</em> expression in OP group exosomes (<em>P</em> < 0.001). D","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117658"},"PeriodicalIF":3.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145152206","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":"Statins and longitudinal changes in vertebral bone mineral density in an emulated target trial: the multi-ethnic study of atherosclerosis","authors":"Elena Ghotbi ,&nbsp;Quincy A. Hathaway ,&nbsp;Roham Hadidchi ,&nbsp;Michael P. Bancks ,&nbsp;David A. Bluemke ,&nbsp;Mei Wan ,&nbsp;R. Graham Barr ,&nbsp;Wendy S. Post ,&nbsp;Matthew Budoff ,&nbsp;Benjamin M. Smith ,&nbsp;João A.C. Lima ,&nbsp;Shadpour Demehri","doi":"10.1016/j.bone.2025.117659","DOIUrl":"10.1016/j.bone.2025.117659","url":null,"abstract":"<div><h3>Background</h3><div>Existing reports on the protective effects of statins on bone health have been conflicting, which may have been related to the diverse selectivity of studied populations. We aimed to evaluate the association between statin initiation and longitudinal changes in vertebral bone mineral density (BMD) over six years.</div></div><div><h3>Methods</h3><div>This emulated target trial used data from the Multi-Ethnic Study of Atherosclerosis (MESA). Participants with a baseline 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥7.5 % at MESA Exam 4 or 5 and no history of prevalent statin use were included. Statin initiators were propensity score matched to non-initiators.</div><div>The primary outcome was longitudinal change in CT-derived multilevel vertebral (T1–T10) BMD, assessed using linear mixed-effects models. Prespecified interaction terms and subsequent subgroup analyses were performed by age, sex, race/ethnicity, body mass index, high-sensitivity C-reactive protein (hs-CRP), physical activity, diabetes status, smoking, and alcohol use. We used an array approach to evaluate the magnitude and prevalence of residual confounding necessary to fully explain our main observation.</div></div><div><h3>Results</h3><div>A total of 384 participants (173 statin initiators; 211 non-initiators) were included in the per-protocol analysis. Statin initiation was associated with a slower decline in vertebral BMD (estimated difference, β = 1.00 g/cm³/year; 95 % CI, 0.65–1.35; <em>p</em> &lt; 0.001), corresponding to a 0.47 % slower annual decline. An unmeasured confounder associated with a 1 % annual relative difference in BMD change would need to be at least three times as prevalent among statin initiators compared with non-initiators to nullify the observed effect size. Subgroup analyses suggested stronger protective associations among participants with impaired fasting glucose or diabetes, lower hs-CRP, and higher physical activity.</div></div><div><h3>Conclusions</h3><div>In this emulated target trial, statin initiation was associated with beneficial bone health effects.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117659"},"PeriodicalIF":3.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119155","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":"Effect of myokines on bone tissue metabolism: a systematic review","authors":"Łukasz Jaśkiewicz ,&nbsp;Anna Romaszko-Wojtowicz ,&nbsp;Grzegorz Chmielewski ,&nbsp;Jakub Kuna ,&nbsp;Magdalena Krajewska-Włodarczyk","doi":"10.1016/j.bone.2025.117654","DOIUrl":"10.1016/j.bone.2025.117654","url":null,"abstract":"<div><div>Myokines are cytokines secreted by skeletal muscle cells. These are cytokines with pleiotropic effects, which have receptors in different organs. Increased secretion of myokines is closely linked to physical activity, through which they affect metabolic processes, signalling pathways, protein expression or cell differentiation.</div><div>This study aimed to demonstrate the possible impact of myokines on bone tissue metabolism based on a review of published scientific papers and to disseminate knowledge on myokines among the clinician community. To carry out an analysis in accordance with the PRISMA guidelines, publications were searched in PubMed, Web of Science and ScienceDirect databases. Out of the total of 644 papers identified in the databases, 18 original studies were analysed.</div><div>The paper outlined the importance of irisin, myostatin, fibroblast growth factor 2, myonectin, and interleukins 6 and 15 in the regulation of bone tissue metabolism. Based on the reviewed studies, irisin consistently demonstrates a pro-osteoblastic effect via the p38 MAPK pathway, while myostatin generally shows an inhibitory effect on bone formation by decreasing muscle mass. Myonectin exhibits a dual role, inhibiting both osteoblast and osteoclast differentiation in murine models, suggesting a complex regulatory function. This analysis considers both pre-clinical studies on cell cultures and animal models, as well as clinical trials in humans. The findings suggest that further research is needed to fully elucidate the in vivo functions and clinical relevance of myokines in bone metabolism, identifying potential therapeutic targets.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117654"},"PeriodicalIF":3.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119156","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":"In D-fence of vitamin D sufficiency– A perspective","authors":"Sarah C. Brennan ,&nbsp;Jenny E. Gunton ,&nbsp;Arthur D. Conigrave ,&nbsp;Rebecca S. Mason ,&nbsp;Christian M. Girgis","doi":"10.1016/j.bone.2025.117657","DOIUrl":"10.1016/j.bone.2025.117657","url":null,"abstract":"<div><div>Vitamin D is well-established in its essential role in maintaining bone health. In recent years, however, researchers have explored potential influences of vitamin D on extra-skeletal functions, with vitamin D deficiency being implicated in several acute and chronic illnesses. Thus, large-scale randomised controlled trials (RCTs) have investigated the impact of vitamin D supplements on conditions including cardiovascular disease, diabetes, sarcopenia, frailty, and even some cancers. In this perspective, we weigh the evidence from these recent trials, drawing a cohesive understanding of vitamin D's potentially diverse effects. Limitations of the field and possible future directions of vitamin D research are considered, along with a discussion of the utility of repetitive vitamin D testing and supplementation for many of these conditions.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117657"},"PeriodicalIF":3.6,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145139637","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":"Feasibility, safety and efficacy of OsteoStrong® in postmenopausal women with low bone mineral density: A pilot study","authors":"Jakub Mesinovic ,&nbsp;Jack R. Ryan ,&nbsp;Carrie-Anne Ng ,&nbsp;Ayse Zengin ,&nbsp;Peter R. Ebeling ,&nbsp;David Scott","doi":"10.1016/j.bone.2025.117656","DOIUrl":"10.1016/j.bone.2025.117656","url":null,"abstract":"<div><div>OsteoStrong® is a brief, near-isometric loading exercise modality that targets bone health improvements by applying forces at relevant anatomical sites using specific equipment during ∼10-min, once weekly sessions. Evidence on adherence, safety and effectiveness is limited. In this single-arm pilot study, we determined the feasibility of 8 months of OsteoStrong® for postmenopausal women with low BMD, and measured changes in bone density, microarchitecture and strength, physical function and body composition. Forty-four postmenopausal women with low BMD (DXA-determined T-score &lt; −1.0 but &gt; − 3.0 at total hip and/or lumbar spine) attended supervised, once-weekly 10–15-min sessions at an OsteoStrong® clinic for 8 months. We calculated 8-month changes in areal BMD (aBMD), trabecular bone scores (TBS), HR-pQCT-determined volumetric BMD (vBMD) and bone microarchitecture and strength, as well as physical function and body composition. Thirty-eight women aged 61.2 ± 5.5 years completed the study. Two adverse events suspected to be intervention-related were recorded. Adherence was 83 ± 28 % overall and 93 ± 9 % in those who completed the study. At 8 months, there were no changes in total hip, femoral neck, and lumbar spine aBMD (all <em>P</em> &gt; 0.05), while TBS decreased (<em>P</em> &lt; 0.05). At the distal radius, total, trabecular and cortical vBMD and cortical thickness decreased (mean change: −0.007 mm [95 %CI: −0.012, −0.002]). At the distal tibia, cortical vBMD decreased and trabecular separation increased (mean change: 0.007 mm [95 %CI: 0.001, 0.012]). Chair stand time (mean change: −0.8 s [95 %CI: −1.2, −0.5]) and stair climb time (mean change: −0.1 s [95 %CI: −0.2, −0.002]) decreased, while SPPB scores increased (mean change: 0.2 [95 %CI: 0.03, 0.38]). There were no changes in other bone, physical function or body composition outcomes. These findings suggest that 8 months of OsteoStrong® does not significantly improve bone density, microarchitecture, or strength in healthy postmenopausal women with low BMD, despite good adherence and safety.</div><div>Australian New Zealand Clinical Trials Registration: ACTRN12620000224921p.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117656"},"PeriodicalIF":3.6,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145126373","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":"The forgotten fat: A systematic review of mandibular adipose content","authors":"Maxime Bedez ,&nbsp;Alexandrine During ,&nbsp;Cécile Olejnik","doi":"10.1016/j.bone.2025.117636","DOIUrl":"10.1016/j.bone.2025.117636","url":null,"abstract":"<div><div>Bone marrow adipose tissue (BMAT) is increasingly recognized for its role in bone physiology and pathology, yet its characteristics in the mandible remain poorly understood compared to long bones and vertebrae. This systematic review aimed to summarize current knowledge on mandibular BMAT in healthy conditions.</div><div>A systematic review was conducted in PubMed, PMC-PubMed, and the Cochrane Library up to March 2025, supplemented by manual searches. Studies were included if they assessed the distribution, quantity, or composition of BMAT in physiological mandibular bone from mammals. Data were synthesized narratively according to PRISMA 2020 guidelines.</div><div>Out of 4356 records, 29 papers involving 3565 mandibles from 9 species were included. The weighted mean dried bone marrow fat fraction in healthy mandibles was 63 %, consistently lower than the 80 % weighted mean for healthy long bones in the included studies. Adipose volume per bone or marrow volume also suggested reduced fat content in the mandible. Fatty acid profiles indicated possible mandibular differences, with lower proportions of palmitic acid (16:0, 22–27 %) and higher stearic acid (18:0, 16 %) compared to long bones. A small study on caribou showed similar patterns, although interspecies variability was also evident.</div><div>Mandibular BMAT is quantitatively lower and compositionally distinct from that of long bones, which may contribute to site-specific responses in bone metabolism. However, heterogeneity in methodologies and lack of data on mineralized tissue lipids underscore the need for standardized protocols and further investigation.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117636"},"PeriodicalIF":3.6,"publicationDate":"2025-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145115344","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":"Dysregulation of bone and myocardial inorganic phosphate transporters and downstream cell signals in early-stage mild chronic kidney disease-mineral and bone disorder: An experimental study","authors":"Evdokia Bogdanova ,&nbsp;Airat Sadykov ,&nbsp;Galina Ivanova ,&nbsp;Olga Beresneva ,&nbsp;Alexandr Zhuravlev ,&nbsp;Natalia Semenova ,&nbsp;Vladimir Sharoyko ,&nbsp;Anton Kutikhin ,&nbsp;Vladimir Dobronravov","doi":"10.1016/j.bone.2025.117653","DOIUrl":"10.1016/j.bone.2025.117653","url":null,"abstract":"<div><div>Chronic kidney disease–mineral and bone disorder (CKD-MBD) significantly contributes to cardiovascular morbidity and mortality in CKD patients, raising questions about the molecular mechanisms linking cardiac and bone abnormalities. In this study, adult male spontaneously hypertensive rats (SHRs) underwent 3/4 nephrectomy (Nx) to induce mild CKD-MBD, with sham-operated SHRs (SO) serving as controls. All animals were fed a standard diet containing 0.6 % phosphorus.</div><div>Exhibiting renal dysfunction comparable to human CKD stage 2, Nx rats had higher levels of serum inorganic phosphate (Pi), calciprotein particles (CPPs), and myocardial phosphorus (P) without differences in serum PTH, FGF23, kidney and bone P content. Compared to controls, the experimental group showed features of lower bone turnover with reduced osteoblast and osteocyte numbers and decreased eroded perimeter, alongside myocardial hypertrophy and fibrosis. In bone and myocardium, reciprocal alterations of a tissue expression of Pi-transporters and MAPK-signals were found. Reduced bone turnover associated with a lower tissue expression of <em>Slc20a1</em> (PiT1) and osteogenic <em>Mapk1</em> (ERK2). In myocardium, <em>Slc20a2</em> (PiT2) and phospho-ERK1/2 expression were upregulated at gene and protein levels in Nx rats <em>versus</em> controls.</div><div>These findings suggest that, in the setting of CKD-associated Pi retention, maladaptive bone and myocardial responses are mediated by the dysregulation of Pi transporters and down-stream ERK1/2 signals.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117653"},"PeriodicalIF":3.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145103182","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":"Prospective evidence for the gut–bone axis in osteoporotic fractures: Insights from genetic prediction and metabolite mediators","authors":"Binjie Zhu ,&nbsp;Xinghao Yu ,&nbsp;Huimin Lu ,&nbsp;Mingzhu Su ,&nbsp;Xiaomin Li ,&nbsp;Jianhua Jin ,&nbsp;Yongmin Yan ,&nbsp;Yi Jin","doi":"10.1016/j.bone.2025.117651","DOIUrl":"10.1016/j.bone.2025.117651","url":null,"abstract":"<div><h3>Objective</h3><div>To clarify the causal role of gut microbiota in osteoporotic fracture and identify underlying metabolic pathways.</div></div><div><h3>Method</h3><div>We constructed genetic risk scores (GRS) for 211 microbial taxa using summary statistics from the MiBioGen consortium, and evaluated their associations with incident osteoporotic fracture in 446,927 participants of European ancestry in the UK Biobank. Osteoporotic fracture was defined by a composite of low bone mineral density (T-score ≤ −1.0 at any site) and clinically confirmed fracture events. Cox proportional hazards models were used for time-to-event analysis, with various covariate adjustment and sex-stratified evaluations. Genome-wide association analysis was performed to identify osteoporotic fracture-related loci. We then (i) performed two-sample Mendelian randomization (MR) with independent outcome GWASs (UK Biobank &amp; FinnGen R12) and (ii) rebuilt GRSs with Dutch Microbiome Project (DMP) instruments for external replication. Mediation analysis explored HDL-related metabolic traits as potential biological intermediates.</div></div><div><h3>Results</h3><div>We identified several microbial GRSs nominally significant associated with osteoporotic fracture risk. Notably, genetically predicted <em>Eubacterium xylanophilum group</em> and <em>Enterobacteriaceae</em> showed consistent associations with increased osteoporotic fracture risk across fully adjusted models (HR = 1.426, <em>P</em> = 0.023), while taxa such as <em>Sellimonas</em>, <em>Ruminococcus2</em>, and <em>Escherichia/Shigella</em> were protective. These associations were stronger in females. GWAS identified one genome-wide significant locus on chromosome 18 (rs146540715) for osteoporotic fracture. Two-sample MR analyses provided suggestive evidence for a potential causal relationship between <em>Eubacterium xylanophilum</em> group and osteoporotic fracture, and directionally consistent associations for Enterobacteriaceae across UKBB and FinnGen datasets. No evidence of pleiotropy was detected. Mediation analysis revealed that <em>Eubacterium xylanophilum group</em> may influence osteoporotic fracture via HDL metabolism, particularly through cholesteryl esters in HDL, explaining 3.34 % of the total effect.</div></div><div><h3>Conclusions</h3><div>Our results provide exploratory genetic and epidemiological support for a link between specific gut microbes and osteoporotic fracture risk (potentially acting in part through HDL-related pathways). Larger independent studies are needed to confirm these associations before any clinical translation is considered.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117651"},"PeriodicalIF":3.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092823","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":"Does exercising during peri- or early post-menopause prevent bone and muscle loss: A systematic review","authors":"Patrick W. Whitman ,&nbsp;Christina J. Alexander ,&nbsp;Leah Kaluta ,&nbsp;Lauren A. Burt ,&nbsp;Leigh Gabel","doi":"10.1016/j.bone.2025.117650","DOIUrl":"10.1016/j.bone.2025.117650","url":null,"abstract":"<div><h3>Introduction</h3><div>The highest rate of bone and muscle loss occurs during the menopause transition. Yet, most clinical exercise trials have excluded peri- and early post-menopausal female participants. This systematic review aimed to determine (1) the effects of exercise on bone and muscle health during the menopause transition; and (2) which types of exercise are most effective for preventing bone and muscle mass loss during the menopause transition.</div></div><div><h3>Methods</h3><div>Articles were retrieved from five electronic databases (MEDLINE, Embase, CENTRAL, CINAHL, and SPORTDiscus). Inclusion criteria included: (1) randomized controlled trial (RCT); (2) 45-to 60-year-old and peri- or early post-menopausal females; (3) reported bone mineral density (BMD) or lean mass.</div></div><div><h3>Results</h3><div>Six studies met inclusion criteria; two evaluated peri-menopausal and four investigated early post-menopausal female participants. All studies had low quality of evidence, and high risk of bias. Strength training, endurance training, and Tai Chi did not improve areal BMD (aBMD) or lean mass during peri-menopause. Strength training and walking benefited total body, hip, spine, femoral neck, and trochanter aBMD and lean mass during early post-menopause. When grouped by exercise type, strength training improved aBMD at all sites but not all strength training studies showed improvements in lean mass. Walking improved total hip aBMD only.</div></div><div><h3>Conclusion</h3><div>Due to the limited number of studies and variety of interventions, it remains inconclusive which training method is optimal to prevent bone and muscle loss during the menopause transition. Future strength training RCTs should include longer duration interventions that compare effects between peri- and early post-menopausal female participants.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117650"},"PeriodicalIF":3.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088501","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":"Altered digit tip blastema differentiation and bone regeneration in skeletally mature Ts65Dn Down syndrome mice","authors":"Sarah M. Wolff ,&nbsp;Ling Yu ,&nbsp;Mingquan Yan ,&nbsp;Regina Brunauer ,&nbsp;Margarita Rodriguez ,&nbsp;David I. Garcia ,&nbsp;Ashima Jain ,&nbsp;Dimas R. Kusuma ,&nbsp;Kirby M. Sherman ,&nbsp;Cole B. Dahlstrom ,&nbsp;Dana Gaddy ,&nbsp;Larry J. Suva ,&nbsp;Lindsay A. Dawson","doi":"10.1016/j.bone.2025.117648","DOIUrl":"10.1016/j.bone.2025.117648","url":null,"abstract":"<div><div>Down syndrome (DS), the result of Trisomy 21 (T21), is associated with accelerated aging and impacts many organ systems across the lifespan, including the musculoskeletal system. Skeletal deficits such as low bone mineral density predispose the T21 population to skeletal injuries, especially as they age, and likely reduce their capacity to repair bone. Previous studies have demonstrated impaired secondary fracture healing in 4-month-old DS mice and diminished bone regeneration in young (2-months-old) DS mice. To investigate how bone regeneration is further impacted in skeletally mature (6-months-old) mice, terminal phalanx (P3) digit tip amputations were performed in a murine model of DS, Ts65Dn mice. The P3 regeneration cascade is characterized by an initial phase of bone degradation followed by intramembranous ossification to restore the amputated bone. These studies demonstrate that the bone regeneration anomalies observed in young Ts65Dn mice are exacerbated in skeletally mature mice, characterized by a complex dysregulation of bone resorption and formation genes. Collectively, skeletally mature Ts65Dn mice show fundamental <em>in vivo</em> deficits in progenitor cell differentiation, cell activity, cell proliferation, and alterations in gene expression associated with diminished regenerative outcomes. Importantly, these deficiencies in bone regeneration in skeletally mature Ts65Dn mice have implications to the adult T21 population as the last several decades have seen substantial increases in the average life span of T21 individuals. If the regenerative defects in Ts65Dn mice are recapitulated during bone healing in the T21 population, this could have profound consequences for this growing population.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117648"},"PeriodicalIF":3.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088569","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}