Bone最新文献

{"title":"The GWAS candidate far upstream element binding protein 3 (FUBP3) is required for normal skeletal growth, and adult bone mass and strength in mice","authors":"Laura M. Watts,&nbsp;Penny C. Sparkes,&nbsp;Hannah F. Dewhurst,&nbsp;Siobhan E. Guilfoyle,&nbsp;Andrea S. Pollard,&nbsp;Davide Komla-Ebri,&nbsp;Natalie C. Butterfield,&nbsp;Graham R. Williams,&nbsp;J.H. Duncan Bassett","doi":"10.1016/j.bone.2025.117472","DOIUrl":"10.1016/j.bone.2025.117472","url":null,"abstract":"<div><div>Bone mineral density (BMD) and height are highly heritable traits for which hundreds of genetic loci have been linked through genome wide association studies (GWAS). FUBP3 is a DNA and RNA binding protein best characterised as a transcriptional regulator of <em>c-Myc</em>, but little is known about its role <em>in vivo</em>. Single nucleotide polymorphisms in <em>FUBP3</em> at the 9q34.11 locus have been associated with BMD, fracture and height in multiple GWAS, but FUBP3 has no previously established role in the skeleton. We analysed <em>Fubp3</em>-deficient mice to determine the consequence of FUBP3 deficiency <em>in vivo</em>. Mice lacking <em>Fubp3</em> had reduced survival to adulthood and impaired skeletal growth. Bone mass was decreased, most strikingly in the vertebrae, with altered trabecular micro-architecture. <em>Fubp3</em> deficient bones were also weak. These data provide the first functional demonstration that <em>Fubp3</em> is required for normal skeletal growth and development and maintenance of adult bone structure and strength, indicating that <em>FUBP3</em> contributes to the GWAS association of 9q34.11 with variation in height, BMD and fracture.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"195 ","pages":"Article 117472"},"PeriodicalIF":3.5,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143733698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dental and craniofacial manifestations in sponastrime dysplasia - An observational study","authors":"Heidi Arponen ,&nbsp;Helena Valta ,&nbsp;Outi Mäkitie","doi":"10.1016/j.bone.2025.117469","DOIUrl":"10.1016/j.bone.2025.117469","url":null,"abstract":"<div><div>Sponastrime dysplasia is an extremely rare autosomal recessive spondyloepimetaphyseal dysplasia characterized by short stature, midface hypoplasia, nasal alterations, and dental anomalies. This is, to date, the first comprehensive report on oral and craniofacial findings, and on subjective oral health-related quality of life as clinically and radiologically examined in two adults with sponastrime dysplasia.</div><div>Both subjects had typical features of sponastrime dysplasia with disproportionate short stature, hypertelorism and midface hypoplasia, and variants in the <em>TONSL</em> gene. One had a severe phenotype (adult height 91 cm), whereas the other exhibited moderate severity (adult height 135 cm). The notable variation in the disorder severity was also expressed in dental manifestations. Dentin dysplasia type I-like abnormalities were seen in tooth eruption and morphology. Dental roots were shortened in both individuals. The individual with severe growth failure had lost several permanent teeth and reported a moderate level of discomfort and impairment due to oral health issues, as evaluated with the Oral Health Impact Profile questionnaire. In contrast, the other individual had a full permanent dentition and minimal negative impact on oral health-related quality of life. Both had short jaw lengths and face height. The anteroposterior jaw relationships were normal. The jaws of the individual with a severe phenotype were retrognathic in relation to the skull base. Both had prominent forehead.</div><div>Due to significant craniofacial and dental involvement, individuals with sponastrime dysplasia should be regularly followed by a multidisciplinary medical team including a dentist, to maintain individuals' oral health and oral health-related quality of life.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"195 ","pages":"Article 117469"},"PeriodicalIF":3.5,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular pH is a critical regulator of osteoclast fusion, size and activation","authors":"Bethan K. Davies ,&nbsp;Andrew J. Skelton ,&nbsp;Mark Hopkinson ,&nbsp;Simon Lumb ,&nbsp;Gill Holdsworth ,&nbsp;Timothy R. Arnett ,&nbsp;Isabel R. Orriss","doi":"10.1016/j.bone.2025.117466","DOIUrl":"10.1016/j.bone.2025.117466","url":null,"abstract":"<div><div>Osteoclast activity is regulated by extracellular pH, whereby bone resorption is near-maximally activated at pH 7.0 but limited at ≥pH 7.4. This study examined the effects of low pH on osteoclast fusion, multi-nucleation, resorption and cell transcriptome. Osteoclasts were cultured on dentine discs at pH 7.4 (control) or pH 7.0 (acidified) for 5–7 days. Osteoclast number and resorptive activity were 1.9-fold and 6.7-fold higher, respectively, in acidified cultures. However, acidified osteoclasts were smaller, with fewer nuclei than controls (53 μm diameter with 9 ± 1 nuclei/cell versus 100 μm with 24 ± 3 nuclei/cell). mRNA expression analysis revealed that osteoclast formation and resorption-associated genes were increased in acidified osteoclasts. Switching mature osteoclasts formed for 5 days at pH 7.4 to acidified conditions decreased cell size 30 % within 4 h, resulting in a 2-fold increase in osteoclast numbers after 24 h. Resorptive activity in cells switched to pH 7.0 was visible within 8 h, and by 24 h resorption area was comparable to continually acidified osteoclasts. MicroCT analysis of dentine discs revealed 24-fold and 6.4-fold increases in resorption pit number in pH-switched osteoclasts relative to control and acidified cultures, respectively. RNAseq showed changes in extracellular pH differentially regulated gene expression, particularly metabolic and cell cycle-associated genes. Our results reveal previously unknown effects of extracellular pH on osteoclasts. Specifically, they show pH is an important modulator of osteoclast fusion and size that regulates the transcriptome. Furthermore, small changes in pH can induce significant morphological changes in osteoclasts and act as on/off switch between formation and resorption in ≤4 h.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"195 ","pages":"Article 117466"},"PeriodicalIF":3.5,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered vertebral biomechanical properties in prostate cancer patients following androgen deprivation therapy","authors":"Fiona G. Gibson ,&nbsp;Margaret A. Paggiosi ,&nbsp;Catherine Handforth ,&nbsp;Janet E. Brown ,&nbsp;Xinshan Li ,&nbsp;Enrico Dall'Ara ,&nbsp;Stefaan W. Verbruggen","doi":"10.1016/j.bone.2025.117465","DOIUrl":"10.1016/j.bone.2025.117465","url":null,"abstract":"<div><div>Androgen deprivation therapy (ADT) for localised and metastatic prostate cancer (PCa) is known to improve survival in patients but has been associated with negative long-term impacts on the skeleton, including decreased bone mineral density (BMD) and increased fracture risk. Generally, dual-enery X-ray absorptiometry (DXA) measurements of areal BMD (aBMD) of vertebrae are used clinically to assess bone health. However, a prediction of vertebral bone strength requires information that aBMD cannot provide, such as geometry and volumetric BMD (vBMD). This study aims to investigate the effect of ADT on the densitometric (aBMD, trabecular vBMD, integral vBMD) and mechanical integrity (failure load and failure strength) of vertebrae, using a combination of DXA, quantitative computed tomography (QCT) and finite element (FE) modelling. For the FE analyses, 3D models were reconstructed from QCT images of 26 ADT treated patients, and their matched controls, collected as part of the ANTELOPE clinical trial. The ADT treated group experienced significantly decreased trabecular and integral vBMD (trabecular vBMD: −18 %, <em>p</em> &lt; 0.001, integral vBMD: −11 %, p &lt; 0.001) compared to control patients that showed no significant temporal changes (trabecular vBMD <em>p</em> = 0.037, integral vBMD <em>p</em> = 0.56). A similar trend was seen in the ADT treated group for the failure load and failure strength, where a decrease of 14 % was observed (<em>p</em> &lt; 0.001). When comparing the proficiency in predicting the mechanical properties from densitometric properties, the integral vBMD performed best in the pooled data (<em>r</em> = 0.86–0.87, <em>p</em> &lt; 0.001) closely followed by trabecular vBMD (<em>r</em> = 0.73–0.75, p &lt; 0.001) with aBMD having a much weaker predictive ability (<em>r</em> = 0.19–0.21, <em>p</em> &lt; 0.01). In conclusion, ADT significantly reduced both the densitometric properties and the mechanical strength of vertebrae. A stronger relationship between both trabecular vBMD and integral vBMD with the mechanical properties than the aBMD was observed, suggesting that such clinical measurements could improve predictions of fracture risk in prostate cancer patients treated with ADT.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"195 ","pages":"Article 117465"},"PeriodicalIF":3.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Klotho senses mechanical stimuli and modulates tension-induced osteogenesis","authors":"Xinrui Men,&nbsp;Wei-Cho Chiou,&nbsp;Xingjian Li,&nbsp;Qiming Li,&nbsp;Xinyi Chen,&nbsp;Kaiwen Zhang,&nbsp;Xiaoge Jiang,&nbsp;Song Chen","doi":"10.1016/j.bone.2025.117464","DOIUrl":"10.1016/j.bone.2025.117464","url":null,"abstract":"<div><div>Delicate external mechanosensing, efficient intracellular mechanotransduction and effective alveolar bone remodeling lay the foundation of orthodontic tooth movement (OTM). Periodontal ligament stem cells (PDLSCs) are thought to be the primary cells that withstand mechanical stimuli and respond to biomechanical signals during orthodontic treatment. Nevertheless, the cellular and molecular mechanisms of orthodontic force-induced mechanosignaling and osteogenesis in PDLSCs still remain unclear. In the present study, we hypothesize that the ageing suppressor, Klotho, is correlated with orthodontic force-triggered mechanical signaling cascades, further contributing to alveolar bone remodeling. This study reveals that Klotho expression is notably upregulated via cytoskeletal-nuclei-mediated epigenetic modifications, consistent with osteogenic differentiation on the tension side during OTM. Additionally, Klotho deficiency undermines tensile force-induced new bone formation in NFκB- and PI3K/Akt-dependent manners. Notably, RNA sequencing (RNA-seq) results and targeted force application experiments unveil that Klotho not only functions as a downstream effector of external stress but also acts as an upstream regulator in mechanical signaling for the first time. In summary, we identify the indispensable role of Klotho in mechanotransduction and alveolar bone formation, which provide a latent target of linking cell senescence to mechanical force in future studies and offer novel insights into orthodontic force-induced tooth movement and bone remodeling.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"195 ","pages":"Article 117464"},"PeriodicalIF":3.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674932","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":"Association of nuclear magnetic resonance-based metabolomics with bone health in the UK Biobank","authors":"Jie Cai ,&nbsp;Huan Huang ,&nbsp;Huaying Hu ,&nbsp;Lu Qi ,&nbsp;Tao Zhou","doi":"10.1016/j.bone.2025.117460","DOIUrl":"10.1016/j.bone.2025.117460","url":null,"abstract":"<div><h3>Objectives</h3><div>The study aimed to explore associations of metabolomic data based on nuclear magnetic resonance (NMR) with the risk of fractures and bone mineral density (BMD).</div></div><div><h3>Methods</h3><div>We included 69,963 participants without fractures at baseline in the UK Biobank. Cox proportional hazard models were used to estimate the associations of metabolomic biomarkers measured by NMR technology with the risk of all fractures and hip fracture. We used principal component analysis (PCA) to obtain uncorrelated principal components (PC), which were further used to estimate the associations of each PC with BMD, all fractures, and hip fracture separately.</div></div><div><h3>Results</h3><div>During a median follow-up of 12.6 years, 3840 incidents of all fractures and 666 incidents of hip fracture were documented. Ninety-four of the 143 metabolomic biomarkers were significantly associated with incident all fractures, and 81 were significantly associated with incident hip fracture. The very low-density lipoprotein (VLDL) subclasses in different lipid constituents were associated with increased BMD at multiple sites, whereas high-density lipoprotein (HDL) subclasses were associated with decreased BMD. Higher concentrations of small (HR per SD increment: 0.92; 95 % CI: 0.88–0.97), medium (HR per SD increment: 0.91; 95 % CI: 0.88–0.94), and large (HR per SD increment: 0.93; 95 % CI: 0.90–0.96) low-density lipoprotein (LDL) particles were associated with a lower risk of all fractures. Similarly, higher VLDL subclasses (excluding very small VLDL particles) were associated with a lower risk of all fractures. Besides, higher levels of lipid constituents (including total lipids, cholesteryl esters, cholesterol, and free cholesterol) of very large and large HDL were associated with an increased risk of all fractures. PC1 (mainly contributed by lipid subclasses of LDL and VLDL), which explained the most variance of individual biomarkers, showed a negative association with the risk of all fractures (<em>P</em> = 7.80E-08). Similar associations were observed for hip fracture.</div></div><div><h3>Conclusions</h3><div>Higher levels of large and very large HDL were associated with an increased risk of fractures, whereas higher lipid subclasses of LDL and VLDL were associated with a lower risk of fracture. Higher levels of VLDL subclasses in different lipid constituents were associated with increased BMD at multiple sites, while higher level of HDL was associated with decreased BMD.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"195 ","pages":"Article 117460"},"PeriodicalIF":3.5,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674597","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":"Molecular mapping of articular cartilage CXCR4 expression after ACL injury via a novel small molecule-based probe","authors":"Michael D. Newton ,&nbsp;Mackenzie M. Fleischer ,&nbsp;Howard W.T. Matthew ,&nbsp;Tristan Maerz","doi":"10.1016/j.bone.2025.117463","DOIUrl":"10.1016/j.bone.2025.117463","url":null,"abstract":"<div><h3>Purpose</h3><div>Molecular imaging is a powerful modality to spatially resolve molecular changes across tissues, but application to articular cartilage remains limited. CXCR4 is an established marker of chondrocyte hypertrophy and potential therapeutic target for osteoarthritis. The purpose of this study was to develop and apply a CXCR4-targeted, near-infrared fluorescent (NIR) probe to a rat model of post-traumatic osteoarthritis (PTOA).</div></div><div><h3>Methods</h3><div>A CXCR4-targeted, small molecule-based NIR probe (“Cy7-AMD”) was synthesized. Sensitivity and specificity of Cy7-AMD to CXCR4 was validated in vitro (HUVECs), and ex vivo (rat osteochondral explants). To induce PTOA, female Lewis rats underwent noninvasive anterior cruciate ligament (ACL) rupture. At 7- and 28-days post-injury, injured/contralateral femora and tibiae were dissected, incubated in Cy7-AMD vs a non-targeting control, and imaged via NIR imaging, as well as conventional and contrast-enhanced micro-computed tomography. Imaging datasets were co-registered, cartilage tissue volumes were segmented, and paired cartilage thickness and NIR signal maps were generated and analyzed for PTOA-relevant changes.</div></div><div><h3>Results</h3><div>Compared to a non-targeting control probe, in vitro and ex vivo assays confirm sensitivity and specificity of Cy7-AMD to CXCR4. Flow cytometry confirmed high correspondence between Cy7-AMD- and antibody-based measurement of CXCR4 expression. Cy7-AMD rapidly equilibrated within cartilage, and fluorescent histology confirmed full-thickness penetration. Injured femoral cartilage exhibited heterogeneous CXCR4 expression, with increased signal deviation compared to contralateral femora. Spatial CXCR4 expression patterns correlated to cartilage thickness patterns; high CXCR4 expression at boundaries of low-thickness lesions suggests an association between CXCR4 expression and cartilage loss.</div></div><div><h3>Conclusions</h3><div>Small molecule-based probes are advantageous for mapping spatial patterns of molecular expression in rodent articular cartilage, deepening our understanding of PTOA progression.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"195 ","pages":"Article 117463"},"PeriodicalIF":3.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143637762","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":"Limb lengthening in individuals with achondroplasia: Analysis of an international survey","authors":"Christoph Beger ,&nbsp;Inês Alves ,&nbsp;Patricia Carl-Innig ,&nbsp;Marco Sessa ,&nbsp;Klaus Mohnike ,&nbsp;Moira S. Cheung","doi":"10.1016/j.bone.2025.117462","DOIUrl":"10.1016/j.bone.2025.117462","url":null,"abstract":"<div><h3>Background</h3><div>Limb lengthening surgery is a contentious option for individuals with achondroplasia. This study aimed to assess real-world experiences, outcomes, and perspectives on limb lengthening in a multinational cohort of individuals with achondroplasia.</div></div><div><h3>Methods</h3><div>A cross-sectional, international online survey on limb lengthening experiences and perspectives was conducted in 11 languages across 16 countries from May until July 2024.</div></div><div><h3>Results</h3><div>Out of 467 responders (229 self-responders, 238 parents/caregivers), 90 (19.3 %) reported undergoing limb lengthening (LL) surgery. The mean age at first surgery was 10.5 years (SD 4.5). On average, respondents underwent 3.7 (SD 2.9) procedures, resulting in 14.5 cm (SD10.4) added and final adult height of 137.1 cm in females and 142.1 cm in males. Significant improvements were described in activities such as car driving, bathing, brushing hair, and wiping after toileting for those who underwent both arm and leg lengthening (<em>p</em> ≤ 0.001). Among respondents, 23 % would recommend the procedure to others and 28 % would not recommend LL. Nearly half of respondents (49 %) was uncertain about recommending LL.</div></div><div><h3>Conclusions</h3><div>This is the largest international survey on LL in achondroplasia with results highlighting some of the differences in perspectives and choices of the individual with achondroplasia and their families, providing real-world evidence of the outcomes of this intervention. While significant functional improvements were reported, a reduced percentage of respondents recommended LL intervention. The findings underscore the existence of a triad when considering limb lengthening in achondroplasia as individual choices and life experiences, socio-cultural environment and access to clinical options.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"195 ","pages":"Article 117462"},"PeriodicalIF":3.5,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660126","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 association between total volume and intensity of moderate-to-vigorous physical activity and incidence of osteoporosis","authors":"Yuting Li ,&nbsp;Yiyi Yang ,&nbsp;Cui Guo ,&nbsp;Honglin Cai","doi":"10.1016/j.bone.2025.117461","DOIUrl":"10.1016/j.bone.2025.117461","url":null,"abstract":"<div><div>It is unclear whether moderate-to-vigorous physical activity (MVPA) and its proportion by vigorous physical activities (VPA) would decrease the risk of osteoporosis. This study aimed to examine a dose-response association between MVPA, VPA ratio, and incident osteoporosis in a large prospective cohort. We conducted a longitudinal analysis using data on MVPA, VPA, and osteoporosis from the UK Biobank prospective cohort study. A total of 368,553 eligible participants were included at baseline. Cox proportional hazard models were used to explore the association of MVPA and VPA with the incidence of osteoporosis for men and women, and trend tests were applied to assess the dose-response relationship between them. During a median follow-up of 12.56 years, 11,788 incident cases of osteoporosis (2016 in men and 9772 in women) were identified. The multivariate-adjusted HR (95%CI) of osteoporosis in the highest compared with lowest quartile of MVPA was 0.61 (0.54–0.69); P-trend &lt; 0.001 for men and 0.84 (0.79–0.89); P-trend &lt; 0.001 for women. In the analyses of proportions of VPA and the risk of osteoporosis, the highest tertile of VPA proportion was associated with the lowest risk of osteoporosis with a HR (95%CI) of 0.74 (0.63–0.86); P-trend &lt; 0.001 for men and 0.80 (0.75–0.86); P-trend &lt; 0.001 for women. A higher MVPA and VPA proportion were associated with decreasing osteoporosis risk in a dose-response manner, respectively, among British aged between 37 and 73 years.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"195 ","pages":"Article 117461"},"PeriodicalIF":3.5,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652414","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":"Impact of vascular calcifications on the risk of fractures in patients with chronic kidney disease","authors":"Alejandro Godoy ,&nbsp;Maria Paula Dionisi ,&nbsp;Anyelo Cardozo ,&nbsp;Pehuén Fernández ,&nbsp;Daniela Porta ,&nbsp;Aldo Tabares ,&nbsp;Carlos Chiurchiu ,&nbsp;Javier de Arteaga ,&nbsp;Jorge de la Fuente ,&nbsp;Walter Douthat ,&nbsp;María Angélica Rivoira","doi":"10.1016/j.bone.2025.117455","DOIUrl":"10.1016/j.bone.2025.117455","url":null,"abstract":"<div><h3>Background</h3><div>The decline in kidney function adversely affects mineral and bone disease, leading to decreased bone mass, increased fractures, and vascular calcifications (VC), particularly in advanced CKD stage 5. This study aimed to identify VC markers to eventually develop personalized therapeutic and preventive strategies in Argentina, where data is limited.</div></div><div><h3>Methods</h3><div>A prospective, observational study included 101 patients on dialysis or pre-dialysis, eligible for kidney transplant at the Private University Hospital of Córdoba from June 2019 to December 2020. Clinical, laboratory, and imaging assessments were conducted, measuring bone mineral density (BMD), pulse wave velocity (PWV), and VC presence. Patients were grouped based on VC status for comparative analysis.</div></div><div><h3>Results</h3><div>VC was found in 28 % of patients, correlating significantly with age, BMI, time on dialysis, deceased donor type, and PWV (<em>p</em> &lt; 0.01). PTH showed a direct correlation with total alkaline phosphatase (ALP), bone-specific alkaline phosphatase, P1NP, osteocalcin, and telopeptides. ALP was significantly higher in the VC group (median = 149.5, range [62–964] vs. median = 106, range [28–449]; <em>p</em> &lt; 0.01). Patients without VC had higher serum albumin levels (OR = 0.16; <em>p</em> = 0.002; CI = 0.05–0.52). Fracture prevalence was 32.1 % in the VC group compared to 13.1 % without VC (<em>p</em> &lt; 0.02), with logistic regression showing VC increased fracture risk threefold (OR = 3.09; <em>p</em> = 0.01; CI = 1.22–7.83).</div></div><div><h3>Conclusion</h3><div>This study highlights the high prevalence of VC and increased fracture risk in CKD stage 5 patients. ALP is a potential serum marker for bone metabolism, while lower serum albumin levels suggest chronic inflammation may contribute to VC development.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"195 ","pages":"Article 117455"},"PeriodicalIF":3.5,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639944","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}