Journal of Bone and Mineral Research最新文献

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Pain in fibrous dysplasia: identifying nociceptive mechanisms in a preclinical model. 纤维结构不良中的疼痛:在临床前模型中识别伤害感受机制。
IF 5.9 1区 医学
Journal of Bone and Mineral Research Pub Date : 2025-06-25 DOI: 10.1093/jbmr/zjaf039
Chelsea Hopkins, Luis Fernandez de Castro, Julie Benthin, Marta Diaz-delCastillo, Pravallika Manjappa, Alison Boyce, Ruth Elena Martinez Mendoza, Juan Antonio Vazquez Mora, Giovanni Emmanuel Lopez-Delgado, Lizeth Yazmin Ponce Gomez, Khaled Elhady Mohamed, John E Linley, Michael T Collins, Juan Miguel Jimenez-Andrade, Anne-Marie Heegaard
{"title":"Pain in fibrous dysplasia: identifying nociceptive mechanisms in a preclinical model.","authors":"Chelsea Hopkins, Luis Fernandez de Castro, Julie Benthin, Marta Diaz-delCastillo, Pravallika Manjappa, Alison Boyce, Ruth Elena Martinez Mendoza, Juan Antonio Vazquez Mora, Giovanni Emmanuel Lopez-Delgado, Lizeth Yazmin Ponce Gomez, Khaled Elhady Mohamed, John E Linley, Michael T Collins, Juan Miguel Jimenez-Andrade, Anne-Marie Heegaard","doi":"10.1093/jbmr/zjaf039","DOIUrl":"10.1093/jbmr/zjaf039","url":null,"abstract":"<p><p>Pain is a common symptom of fibrous dysplasia (FD), a rare mosaic disorder characterized by fibro-osseous lesions in the bone. Despite the prevalence of pain in FD patients, there is little knowledge about the nociceptive mechanisms and few efficacious treatments. As such, understanding FD pain is essential for patient care. The overall aim of this study was to identify nocifensive behaviors and potential underlying mechanisms in a transgenic mouse model of FD, previously shown to display high face and translational validity. Significant nocifensive behaviors were observed in FD mice (male and female), compared to control mice in the burrowing, grid hanging, home cage activity, and wheel running assays. These changes corresponded to lesion development, as visualized by X-ray imaging. Behavioral deficits improved when analgesics were administered, indicating a nociceptive origin. Tibias and femurs from FD mice demonstrated characteristic FD lesions and the presence of mono- and multi-nucleated CD68+ cells, calcitonin gene-related peptide sensory nerve fibers, and vascularization. Lumbar dorsal root ganglia from male FD mice displayed increased staining for activating transcription factor-3 and tyrosine hydroxylase neurons. No difference was observed in the spinal cords between the FD and control groups for glial cell presence and neuropeptide expression. Bone marrow stromal cells were obtained from FD and control mice and cultured in vitro. FD cells developed an increased concentration of inflammatory cytokines (IL-6, tumor necrosis factor-alpha), chemokines (monocyte chemoattractant protein, keratinocyte chemoattractant/human growth-regulated oncogene), and nerve growth factor as compared to controls. Taken together, this study demonstrated for the first time that nociceptive mechanisms such as axonal growth in FD lesions, nerve injury, and inflammation may contribute to FD pain, and it provides a foundation for conducting further studies of pain- and disease-modifying therapeutics for FD patients.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"891-903"},"PeriodicalIF":5.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075014","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}
引用次数: 0
You are what you breathe? Metabolites may begin to explain the link between air pollution and bone damage. 你就是你呼吸的东西?代谢物可能开始解释空气污染和骨骼损伤之间的联系。
IF 5.1 1区 医学
Journal of Bone and Mineral Research Pub Date : 2025-06-25 DOI: 10.1093/jbmr/zjaf070
Stefaan W Verbruggen
{"title":"You are what you breathe? Metabolites may begin to explain the link between air pollution and bone damage.","authors":"Stefaan W Verbruggen","doi":"10.1093/jbmr/zjaf070","DOIUrl":"10.1093/jbmr/zjaf070","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"825-826"},"PeriodicalIF":5.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144092424","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}
引用次数: 0
The impact of segmentation approach on HR-pQCT microarchitectural and biomechanical metrics depends on bone structure. 分割方法对HR-pQCT微结构结果指标和微有限元生物力学估计的影响取决于骨微结构。
IF 5.1 1区 医学
Journal of Bone and Mineral Research Pub Date : 2025-06-25 DOI: 10.1093/jbmr/zjaf060
Minhao Zhou, Gabriella Ramil, Isabel Yu, Saghi Sadoughi, Isra Saeed, Bo Fan, Andrew J Burghardt, Tiffany Y Kim, Joachim H Ix, Galateia J Kazakia
{"title":"The impact of segmentation approach on HR-pQCT microarchitectural and biomechanical metrics depends on bone structure.","authors":"Minhao Zhou, Gabriella Ramil, Isabel Yu, Saghi Sadoughi, Isra Saeed, Bo Fan, Andrew J Burghardt, Tiffany Y Kim, Joachim H Ix, Galateia J Kazakia","doi":"10.1093/jbmr/zjaf060","DOIUrl":"10.1093/jbmr/zjaf060","url":null,"abstract":"<p><p>High-resolution peripheral quantitative computed tomography (HR-pQCT), combined with micro-finite element (μFE) models, provide a powerful clinical research tool for evaluating bone structure-function relationships with musculoskeletal disorders and bone-targeting treatments. Based on ex vivo cadaveric phantom scans, the Laplace-Hamming (LH) segmentation approach, compared to the standard segmentation approach, improves the accuracy and precision of microarchitecture evaluation using second-generation HR-pQCT scanners. However, the effect of LH segmentation on in vivo scans acquired from clinically relevant cohorts with disease-specific bone microarchitecture (eg, patients with end-stage kidney disease) has not been investigated. Additionally, the effect of LH segmentation on μFE biomechanical estimations remains unexplored, defining the objectives of the current study. Findings from the current study demonstrated that LH segmentation, compared to standard segmentation, reduced structure-dependent bias in HR-pQCT microarchitectural and μFE biomechanical metrics. Specifically, trabecular bone volume fraction (Tb.BV/TV), trabecular thickness (Tb.Th), and cortical pore diameter (Ct.Po.Dm) were particularly sensitive to segmentation strategy. Due to the structure dependence of the standard segmentation approach, applying LH segmentation can alter the results of between-cohort comparisons, potentially leading to different clinical interpretations. For example, differences in cortical porosity (Ct.Po) between healthy participants and patients with end-stage kidney disease were only significant when evaluated using the standard segmentation approach. Thus, it is important that investigators consider the segmentation approach utilized when interpreting HR-pQCT outcome metrics for disease progression or drug effects assessments. Additionally, a structure-based parameter (Tb.Th$times$Ct.Po.Dm) that robustly predicted the effect of LH segmentation on μFE biomechanical estimations was established. The predictive power of this parameter highlights the importance of incorporating LH segmentation when evaluating cohorts with documented disease-specific alterations in bone microstructure (eg, changes in Tb.Th and Ct.Po.Dm), such as patients with type 2 diabetes.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"868-880"},"PeriodicalIF":5.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956337","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}
引用次数: 0
Expression of Concern: Comparative cardiovascular safety of romosozumab versus bisphosphonates in Japanese patients with osteoporosis: a new-user, active comparator design with instrumental variable analyses. 关注的表达:比较romosozumab与双膦酸盐在日本骨质疏松症患者的心血管安全性:一个新的用户,积极的比较设计与工具变量分析。
IF 5.1 1区 医学
Journal of Bone and Mineral Research Pub Date : 2025-06-25 DOI: 10.1093/jbmr/zjaf074
{"title":"Expression of Concern: Comparative cardiovascular safety of romosozumab versus bisphosphonates in Japanese patients with osteoporosis: a new-user, active comparator design with instrumental variable analyses.","authors":"","doi":"10.1093/jbmr/zjaf074","DOIUrl":"10.1093/jbmr/zjaf074","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"906"},"PeriodicalIF":5.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140950","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}
引用次数: 0
Metabolomic evaluation of air pollution-related bone damage and potential mediation in Women's Health Initiative participants. 空气污染相关骨损伤的代谢组学评价及其在妇女健康倡议参与者中的潜在中介作用。
IF 5.1 1区 医学
Journal of Bone and Mineral Research Pub Date : 2025-06-25 DOI: 10.1093/jbmr/zjaf059
Diddier Prada, Vrinda Kalia, Feng Gao, Kathryn Rexrode, Charles Kooperberg, Alex Reiner, Raji Balasubramanian, Hui-Chen Wu, Carolyn J Crandall, Carol Horowitz, David Cantu-de-Leon, Claudia Garcia-Cuellar, Andrea Ramirez, Jonathan González-Ruiz, Duanping Liao, Jeff Yanosky, James D Stewart, Eric A Whitsel, Andrea A Baccarelli
{"title":"Metabolomic evaluation of air pollution-related bone damage and potential mediation in Women's Health Initiative participants.","authors":"Diddier Prada, Vrinda Kalia, Feng Gao, Kathryn Rexrode, Charles Kooperberg, Alex Reiner, Raji Balasubramanian, Hui-Chen Wu, Carolyn J Crandall, Carol Horowitz, David Cantu-de-Leon, Claudia Garcia-Cuellar, Andrea Ramirez, Jonathan González-Ruiz, Duanping Liao, Jeff Yanosky, James D Stewart, Eric A Whitsel, Andrea A Baccarelli","doi":"10.1093/jbmr/zjaf059","DOIUrl":"10.1093/jbmr/zjaf059","url":null,"abstract":"<p><p>Ambient air pollution has been associated with bone damage. However, no studies have evaluated the metabolomic response to air pollutants and its potential influence on bone health in postmenopausal women. We analyzed data from Women's Health Initiative (WHI) participants with plasma samples. Whole-body, TH, FN, and spine BMD were determined using DXA at enrollment and follow-up visits (years 1, 3, 6, and 9 visits; Y1, Y3, Y6, Y9, respectively). Geocoded, participant address-specific, daily particulate matter nitrogen oxide (NO), nitrogen dioxide (NO2), particulate matter ≤10 μm (PM10), and sulfur dioxide (SO2) concentrations were averaged over 1-, 3-, and 5-yr periods before plasma sampling for metabolomic assessments (at baseline and Y1 visit). The averages were then integrated using masked WHI participant identifiers. Statistical analyses included multivariable-adjusted linear mixed models, pathway analyses, and mediation modeling. At all averaging periods, NO, NO2, and SO2, but not PM10, were associated with taurine, inosine, and C38:4 phosphatidylethanolamine (PE). We found a partial potential mediation of C38:4 PE in the association between 1-yr average NO and LS BMD (p-value: .032). This is the first study suggesting phospholipids may partially mediate air pollution-related bone damage in postmenopausal women.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"834-846"},"PeriodicalIF":5.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954301","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}
引用次数: 0
Vitamin D and tibial bone density, geometry, and microarchitecture in male military recruits: an observational study and randomized controlled trial. 维生素D与男性新兵胫骨骨密度、几何形状和微结构:一项观察性研究和随机对照试验。
IF 5.1 1区 医学
Journal of Bone and Mineral Research Pub Date : 2025-06-25 DOI: 10.1093/jbmr/zjaf064
Thomas J O'Leary, Rachel M Izard, Sarah Jackson, Neil P Walsh, Alexander T Carswell, Samuel J Oliver, Donald Allan, Lesley E Rhodes, Jonathan C Y Tang, William D Fraser, Julie P Greeves
{"title":"Vitamin D and tibial bone density, geometry, and microarchitecture in male military recruits: an observational study and randomized controlled trial.","authors":"Thomas J O'Leary, Rachel M Izard, Sarah Jackson, Neil P Walsh, Alexander T Carswell, Samuel J Oliver, Donald Allan, Lesley E Rhodes, Jonathan C Y Tang, William D Fraser, Julie P Greeves","doi":"10.1093/jbmr/zjaf064","DOIUrl":"10.1093/jbmr/zjaf064","url":null,"abstract":"<p><p>Vitamin D may mitigate bone stress injuries in military training by modulating changes in bone. This cross-sectional observational study (Study 1) and randomized controlled trial (Study 2) investigated associations between vitamin D metabolites and tibial structure and density, and the effect of vitamin D supplementation on tibial adaptations to military training. A total of 343 (Study 1) and 194 (Study 2) male British Army recruits participated. Circulating vitamin D metabolites (biologically \"active\" and \"inactive\") and tibial structure were measured in participants during week 1 and week 12 (Study 2 only) of initial military training. Associations between vitamin D metabolites and HRpQCT outcomes at week 1 were tested in Study 1. Participants in Study 2 were randomly assigned to vitamin D (oral pill or simulated sunlight) or placebo (placebo pill or placebo simulated sunlight) supplementation for 12 wk designed to achieve vitamin D sufficiency. There was no association between total 25(OH)D or vitamin D receptor single-nucleotide polymorphisms and any measure of density, geometry, or microarchitecture (p ≥ .063). Higher 1,25(OH)2D was associated with lower cortical porosity and perimeter (p ≤ .040). Higher total 24,25(OH)2D was associated with higher trabecular number and lower trabecular thickness (p = .016). Higher 25(OH)D:24,25(OH)2D (VMR 1) was associated with higher trabecular thickness, trabecular separation, and cortical porosity (p ≤ .034). Higher 1,25(OH)2D:24,25(OH)2D (VMR 2) was associated with lower trabecular number, and higher trabecular spacing and thickness (p ≤ .035). There was no effect of vitamin D supplementation on any tibial outcome. Training decreased trabecular area (-0.1%), thickness (-4.4%), and separation (-2.1%), and increased cortical thickness (0.8%) and area (0.9%) (p ≤ .042). Vitamin D metabolites and their ratios were associated with tibial size and microarchitecture, but vitamin D supplementation had no impact on the adaptive response to military training.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"847-859"},"PeriodicalIF":5.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954306","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}
引用次数: 0
Increased risk of vertebral fractures and reduced risk of femur fractures in patients with chronic hypoparathyroidism: a nationwide cohort study in Sweden. 慢性甲状旁腺功能低下患者椎体骨折风险增加,股骨骨折风险降低:瑞典一项全国队列研究
IF 5.1 1区 医学
Journal of Bone and Mineral Research Pub Date : 2025-06-25 DOI: 10.1093/jbmr/zjaf061
Sigridur Björnsdottir, Wafa Kamal, Michael Mannstadt, Outi Mäkitie, Tim Spelman, Olle Kämpe, Bente L Langdahl
{"title":"Increased risk of vertebral fractures and reduced risk of femur fractures in patients with chronic hypoparathyroidism: a nationwide cohort study in Sweden.","authors":"Sigridur Björnsdottir, Wafa Kamal, Michael Mannstadt, Outi Mäkitie, Tim Spelman, Olle Kämpe, Bente L Langdahl","doi":"10.1093/jbmr/zjaf061","DOIUrl":"10.1093/jbmr/zjaf061","url":null,"abstract":"<p><p>Patients with chronic hypoparathyroidism (hypoPT) have reduced bone remodeling, leading to increased bone density and abnormalities in microarchitecture and bone strength. Whether these patients have an increased fracture risk remains unclear. This study aimed to evaluate the risk of major osteoporotic fracture (MOF), osteoporosis diagnoses, and osteoporosis medication use in patients with chronic hypoPT in Sweden. Subtypes of fractures were also assessed. Using the Swedish National Patient Register, the Prescribed Drug Register, and the Total Population Register, we identified 1915 patients with chronic hypoPT treated with active vitamin D between 1997 and 2018, and 15 838 matched controls. After adjustment, patients with chronic hypoPT did not have a higher risk of MOF compared to controls (HR 0.93; 95% CI: 0.69-1.26). However, they had a higher risk of vertebral fractures (HR 1.55; 95% CI: 1.12-2.14) and a lower risk of femur fractures (HR 0.70; 95% CI: 0.50-0.98) compared to controls. They were more often diagnosed with osteoporosis (HR 1.54; 95% CI: 1.21-1.95) but less frequently prescribed osteoporosis medication (HR 0.69; 95% CI: 0.54-0.88) compared to controls. No difference in the MOF risk was observed between females and males (p for interaction = 0.872) or between patients with surgical and non-surgical chronic hypoPT (p for interaction = 0.072). In this large Swedish cohort, chronic hypoPT was not associated with an increased risk of MOF. Vertebral fracture risk was higher, while the femur fracture risk was lower compared to controls. Despite higher prevalence of osteoporosis diagnoses, these patients received less frequently osteoporosis medications.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"860-867"},"PeriodicalIF":5.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143954419","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}
引用次数: 0
Anti-transforming growth factor-β treatment shows increased bone mass and strength in a novel mouse model for osteogenesis imperfecta type I. 抗tgf -β治疗在一种新型成骨不全I型小鼠模型中显示出骨量和强度的增加。
IF 5.1 1区 医学
Journal of Bone and Mineral Research Pub Date : 2025-06-25 DOI: 10.1093/jbmr/zjaf068
Ellen Busschers, Yuqing Chen-Everson, Mary Adeyeye, I-Wen Song, Emily Busse, Alexis Castellon, Oscar Ruiz, Nicole Meyers, Yangjin Bae, Catherine Ambrose, Brendan Lee
{"title":"Anti-transforming growth factor-β treatment shows increased bone mass and strength in a novel mouse model for osteogenesis imperfecta type I.","authors":"Ellen Busschers, Yuqing Chen-Everson, Mary Adeyeye, I-Wen Song, Emily Busse, Alexis Castellon, Oscar Ruiz, Nicole Meyers, Yangjin Bae, Catherine Ambrose, Brendan Lee","doi":"10.1093/jbmr/zjaf068","DOIUrl":"10.1093/jbmr/zjaf068","url":null,"abstract":"<p><p>Anti-transforming growth factor beta (TGF-β) is a promising approach for the treatment of osteogenesis imperfecta (OI). To date, preclinical and clinical studies for the use of anti-TGF-β therapy have focused on moderate to severe OI caused by qualitative defects in collagen. However, the majority of OI patients are represented by type I OI. Mutations resulting in the haploinsufficiency of type I collagen is the cause of OI type I in the majority of patients. To study the effect of anti-TGF-β therapy in type I OI, we generated a novel mouse model for OI type I. CMV-CRE mice were crossed to mice where Col1a1 was floxed between exon 2 and 5 to create a full body heterozygous deletion of Col1a1. Haploinsufficiency of Col1a1 in the tibia was confirmed by decreased Col1a1 mRNA and protein expression. Comparable to OI patients, we observed reduced bone mass by μCT in these Col1a1+/- mice. Biomechanical measurements showed a decrease in bone strength and an increase in bone brittleness. Histomorphometric analysis showed an increase in osteoclast number and a trend towards increased osteoblast number supporting a high bone turnover phenotype, similar to OI type I patients. Upon treatment with a pan anti-TGF-β antibody, 1D11, Col1a1+/- mice showed increased bone mass and improved ultimate strength, but measures of ductility did not show improvement. Overall, our findings support expanding the study of anti-TGF-β treatment to OI caused by haploinsufficiency of type I collagen.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"881-890"},"PeriodicalIF":5.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188749/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958789","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}
引用次数: 0
Dive into the bone: new insights into molecular mechanisms of cancer bone invasion. 深入骨骼:癌症骨侵袭分子机制的新见解。
IF 5.1 1区 医学
Journal of Bone and Mineral Research Pub Date : 2025-06-25 DOI: 10.1093/jbmr/zjaf054
Masayuki Tsukasaki
{"title":"Dive into the bone: new insights into molecular mechanisms of cancer bone invasion.","authors":"Masayuki Tsukasaki","doi":"10.1093/jbmr/zjaf054","DOIUrl":"10.1093/jbmr/zjaf054","url":null,"abstract":"<p><p>Cancer-bone interactions have been investigated primarily in the context of bone metastasis. However, hematogenous spread is not the only route by which cancer cells enter the bone. Certain types of cancer, including head and neck squamous cell carcinoma (HNSCC), directly invade the bone tissue because of the close anatomical relationship between the bone and primary lesions. This type of invasion significantly worsens prognosis and quality of life; however, comparatively less attention has been paid to the mechanisms of primary tumor-related bone invasion. A recent study demonstrated that the periosteum thickens in response to the proximity of tumors and functions as a physical barrier against tumor progression. Periosteum thickening occurs at the pre-invasive stage, a key time point that has been overlooked in previous studies, and critically contributes to the inhibition of cancer invasion into the bone. This study provides insights into the mechanisms of localized bone invasion by cancer, highlights the anti-tumor effects of non-immune stromal cells, and offers a new concept of \"stromal defense against cancer,\" extending the horizon of cancer biology. Here, I discuss the tumor-host interactions during multiple steps of cancer invasion into the bone and how the emerging concepts from bone research contribute to the understanding of the pathogenesis and development of new therapeutic strategies for malignancies in the bone and beyond.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"827-833"},"PeriodicalIF":5.1,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957880","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}
引用次数: 0
Infigratinib low dose therapy is an effective strategy to treat hypochondroplasia. 非加替尼低剂量治疗是治疗软骨发育不良的有效策略。
IF 5.1 1区 医学
Journal of Bone and Mineral Research Pub Date : 2025-06-24 DOI: 10.1093/jbmr/zjaf088
Benoit Demuynck, Bhavik P Shah, Franck Mayeux, Laurine Vasseur, Florent Barbault, Jixin Ding, Morgan Paull, Tejaswini Reddi, Elena Muslimova, Laurence Legeai-Mallet
{"title":"Infigratinib low dose therapy is an effective strategy to treat hypochondroplasia.","authors":"Benoit Demuynck, Bhavik P Shah, Franck Mayeux, Laurine Vasseur, Florent Barbault, Jixin Ding, Morgan Paull, Tejaswini Reddi, Elena Muslimova, Laurence Legeai-Mallet","doi":"10.1093/jbmr/zjaf088","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf088","url":null,"abstract":"<p><p>Hypochondroplasia is a rare genetic form of skeletal dysplasia, caused by gain-of-function pathogenic variants in the fibroblast growth factor receptor 3 (FGFR3). It is characterized by disproportionate short stature and has a wide spectrum of clinical features. Currently, there are no precision therapeutic options approved for hypochondroplasia. Infigratinib is an orally bioavailable FGFR1-3 selective tyrosine kinase inhibitor in development for achondroplasia and hypochondroplasia. Infigratinib acts directly at the source of the pathophysiological cause of both conditions by inhibiting the phosphorylation of FGFR3 and attenuating both main downstream signaling pathways that are involved in the conditions. Results from a Phase 2 study support the concept that infigratinib has a potential to improve bone growth in achondroplasia. We report results of a step-wise evaluation of the therapeutic relevance of infigratinib for hypochondroplasia: in silico assessment of infigratinib with hypochondroplasia associated FGFR3 variants suggest strong interaction; in vitro, infigratinib showed potent inhibitory effect; in a mouse model of hypochondroplasia (Fgfr3N534K/+), infigratinib resulted in significant improvement in skeletal growth. These data in addition to the clinical results from the Phase 2 study conducted in children with achondroplasia provide support for the development of infigratinib in the treatment of hypochondroplasia.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144525723","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}
引用次数: 0
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