Journal of Bone and Mineral Research最新文献

{"title":"From frail bones that could not last long to strong bones that support a good and long life-the story of osteogenesis imperfecta.","authors":"Peter Vestergaard","doi":"10.1093/jbmr/zjaf133","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf133","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147637423","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":"AnnexinA1-Dectin 1 axis is a key regulator of osteoclastogenesis underlying irradiation induced bone loss in male mice.","authors":"Gulnaz Guliyeva, Flora Nguemedjio Foko Takile, Verena Stallfort, Anja Derer, Benjamin Frey, Pooja Gupta, Manuel Weber, Leah Trumet, Georg Schett, Aline Bozec, Bettina Grötsch","doi":"10.1093/jbmr/zjag062","DOIUrl":"https://doi.org/10.1093/jbmr/zjag062","url":null,"abstract":"<p><p>The molecular mechanisms linking immune cell signaling to osteoclastogenesis remain incompletely defined. Here, we identify an Annexin A1 (AnxA1)-Dectin-1 axis as a key driver of osteoclast differentiation. Dectin-1 (CLEC7A), a myeloid C-type lectin receptor best known for β-glucan recognition, is shown to bind the endogenous ligand AnxA1 on pre-osteoclasts, thereby promoting their maturation. In Dectin-1 deficient mice, reduced osteoclast numbers resulted in increased bone volume, whereas β-glucan-induced Dectin-1 activation enhanced osteoclastogenesis. Within the bone marrow niche, AnxA1 was abundantly expressed on B220+ B cells, and γ-irradiation markedly increased its surface translocation both in vitro and in vivo. γ-irradiated B220+ B cells exhibited strong Dectin-1 binding capacity and robustly stimulated osteoclast differentiation in a Dectin-1-dependent manner. These findings establish the AnxA1-Dectin-1 interaction as a critical immune-skeletal communication pathway, revealing a mechanism by which radiation exposed immune cells can accelerate bone resorption. Targeting this axis offers a potential strategy to mitigate radiation-induced bone degradation and preserve skeletal homeostasis.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147588900","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":"Serum albumin and the Prognostic Nutritional Index independently predict fracture risk in elderly women.","authors":"Raju Jaiswal, Berit A M Larsson, Maria Åberg, Lisa Johansson, Kristian F Axelsson, Mattias Lorentzon","doi":"10.1093/jbmr/zjag063","DOIUrl":"https://doi.org/10.1093/jbmr/zjag063","url":null,"abstract":"<p><p>Serum albumin and the Prognostic Nutritional Index (PNI), based on albumin and lymphocytes, are markers of nutritional and inflammatory status and have been associated with frailty and adverse outcomes in older adults. However, their relationship with fracture risk and underlying mechanisms remains unclear. In this prospective cohort study, 2,966 community-dwelling Swedish women aged 75-80 years were followed for a median of 8.0 years. At baseline, blood samples were collected, bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry (DXA), and bone microarchitecture and composition were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Fractures were verified through regional X-ray archives, and injurious falls and mortality were obtained from registers. Physical function was assessed using standardized tests. Cox proportional hazards models and competing risk analyses were applied. PNI was defined as PNI = serum albumin (g/L) + 5 × total lymphocyte count (109/L). In total, 229 hip fractures, 789 major osteoporotic fractures (MOF), 1,059 fractures of any kind, 499 injurious falls, and 551 deaths occurred. Lower albumin and PNI were independently associated with increased risk of MOF (HR per 1 SD decrease: 1.13 [95% CI 1.06-1.22] and 1.18 [1.05-1.31], respectively; both p<0.01) and any fracture (HR: 1.12 [1.05-1.19] and 1.17 [1.07-1.29], respectively; both p<0.01), even after adjustment for clinical risk factors, femoral neck BMD and physical function. Albumin, and to a lesser extent PNI, was consistently associated with better physical function and lower risk of injurious falls and mortality. No significant associations were found between albumin or PNI and DXA-derived BMD, and only limited and inconsistent associations with HR-pQCT parameters. In conclusion, serum albumin and PNI independently predicted fracture risk in elderly women; however, the underlying mechanisms remain to be elucidated. Future studies should explore its contribution to fracture prediction models.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147588898","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":"Differences and similarities in cortical bone of the femur between donors with and without type 2 diabetes.","authors":"Emily Berestesky, Sasidhar Uppuganti, Daniel Y Dapaah, Daniel Fernandes, Nick Livingston, David Lutsky, Yumeng Zhang, Alicia M Hymel, Jacquelyn S Pennings, Paul Voziyan, Mark D Does, Thomas L Willett, Jeffry S Nyman","doi":"10.1093/jbmr/zjaf173","DOIUrl":"10.1093/jbmr/zjaf173","url":null,"abstract":"<p><p>For a given BMD, adults with type 2 diabetes (T2D) have greater fracture risk than adults without the disease. To test the hypothesis that T2D lowers the fracture resistance of human cortical bone by negatively altering the bone matrix quality, we acquired cadaveric femurs from 120 female and male donors >50 yr old: 60 without diabetes (Ctrl) and 60 with T2D for ≥10 yr. We scanned a cross-section from each diaphysis using ex vivo micro-CT (μCT), followed by cyclic reference point indentation (cRPI: 0-10 N for 20 cycles) and impact micro-indentation on the medial surface. From the medial quadrant, a tensile specimen and a single-edge notched beam (SENB) were mechanically tested to assess differences in fracture resistance. Multiple techniques characterized the organic matrix within the SENB. The cortical bone area and thickness of the diaphysis were higher in T2D than in Ctrl. The average creep indentation distance of periosteal bone tissue was significantly lower with T2D suggesting greater resistance to micro-indentation. Bone material strength index trended to be lowering in T2D than in Ctrl but only when the comparison was adjusted for age, sex, and BMI. There were also T2D-related differences in the organic matrix: (1) higher non-enzymatic and mature enzymatic crosslinks, (2) higher fluorescent advanced glycation end-products, and (3) higher thermal stability. Despite these tissue- and molecular-level differences, mechanical properties of cortical bone were similar between the 2 groups. Tensile strength was lower (p = .035), while pentosidine was higher (p = .006) in donors with CKD than donors without kidney disease, but the difference in strength (p = .055) and pentosidine (p = .151) were not strictly significant when adjusting for covariates. The elevated fracture risk in T2D may not be a problem of poor mechanical properties of cortical bone, despite alterations in the organic matrix.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"434-446"},"PeriodicalIF":5.9,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145561920","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":"Liquid-liquid phase separation in physiological and pathophysiological bone turnover.","authors":"Yuxian Xia, Weijian Xu, Xiaofeng Yang, Xiaoyuan Huang, Huizhi Xie, Kelvin W K Yeung, Zhijian Xie, Yanhua Lan","doi":"10.1093/jbmr/zjaf178","DOIUrl":"10.1093/jbmr/zjaf178","url":null,"abstract":"<p><p>The regulation of bone physiology and pathophysiology is intricately controlled by a complex interplay of cellular and molecular mechanisms. In these processes, the precise spatiotemporal coordination of biological activities in bone-resident cells plays a central role. Recently, liquid-liquid phase separation (LLPS), a mechanism underlying membraneless biomolecular condensate formation, has emerged as a transformative area of research. Liquid-liquid phase separation refers to the phase transition of biomolecules under specific conditions, leading to the formation of biomolecular condensates, which orchestrate diverse cellular functions. In this review, we provide a comprehensive synthesis of how LLPS influences bone turnover, focusing on its role in regulating bone homeostasis and its dysregulation in bone disease pathogenesis. Furthermore, aside from addressing the current challenges and limitations in this nascent field, we explore the implications of LLPS in bone regeneration, preventive strategies, and precision medicine. Despite LLPS research being in its early stages, its rapid advancement underscores its crucial role in bone biology and highlights the urgent need to integrate LLPS insights with translational approaches to advance therapeutic interventions for bone disorders.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"366-381"},"PeriodicalIF":5.9,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145627082","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":"DXA-derived hip shape is associated with hip fracture: a longitudinal study of 38 123 UK Biobank participants.","authors":"Sophie Scott, Asad Hashmi, Raja Ebsim, Mijin Jung, Fiona R Saunders, Jennifer S Gregory, Richard M Aspden, Claudia Lindner, Timothy Cootes, Nicholas C Harvey, Jonathan H Tobias, Benjamin G Faber, Rhona A Beynon","doi":"10.1093/jbmr/zjaf171","DOIUrl":"10.1093/jbmr/zjaf171","url":null,"abstract":"<p><p>Despite advancements in fracture prediction tools and osteoporosis management, hip fractures remain a significant consequence of bone fragility, carrying a 22% 1-yr mortality rate. Hip geometric measures (GMs) have been associated with fracture risk; however, their strong correlation hinders the identification of independent influences, leaving their relative predictive value unclear. Statistical shape modeling (SSM) provides a more holistic assessment of hip shape compared to using predetermined GMs. This study aimed to evaluate whether SSM-derived hip shape from DXA scans can predict hip fracture, independently of individual GMs. Previously, we applied SSM to left hip DXA images in UK Biobank-a large prospective cohort with linked hospital records-generating 10 orthogonal hip shape modes (HSMs) that explained 86% of shape variance. Additionally, FN width (FNW), femoral head diameter (FHD), and hip axis length (HAL) were derived from these DXAs. In the current analysis, Cox proportional hazard models, adjusted for age, sex, height, weight, BMD, and GMs (FNW, HAL, and FHD), were used to examine the longitudinal associations between each HSM and first incident hospital diagnosed hip fracture. A Bonferroni adjusted p-value threshold (p < .004) was used to account for the 13 exposures. Among the 38 123 participants (mean age 63.7 yr; 52% female; mean follow-up 5 yr), 133 (0.35%) experienced subsequent hip fracture. HSM2, characterized by a narrower FNW, a higher neck shaft angle, and reduced acetabular coverage, showed a strong association with hip fracture risk (HR: 1.32, 95% CI: 1.11-1.58, p: 1.47 × 10-3), which persisted after full adjustment (1.30, 1.09-1.55, 3.27 × 10-3). There was no evidence for an association with other HSMs. These findings suggest that DXA-derived hip shape is associated with hip fracture risk independently of BMD and GMs. Incorporating global hip shape into fracture risk assessment tools could enhance prediction accuracy and inform targeted interventions.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"396-405"},"PeriodicalIF":5.9,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7618572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145561953","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":"Systemic bone loss during fracture healing: new evidence from HR-pQCT analyses.","authors":"Bettina M Willie, Seyedmahdi Hosseinitabatabaei","doi":"10.1093/jbmr/zjaf073","DOIUrl":"10.1093/jbmr/zjaf073","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"339-340"},"PeriodicalIF":5.9,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145090783","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":"Treat to target in osteoporosis-the time is right.","authors":"Peter R Ebeling","doi":"10.1093/jbmr/zjaf151","DOIUrl":"10.1093/jbmr/zjaf151","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"345-347"},"PeriodicalIF":5.9,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311953","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":"Considerations regarding the use of romosozumab in a patient at high risk for cardiovascular disease.","authors":"Michael R McClung","doi":"10.1093/jbmr/zjaf164","DOIUrl":"10.1093/jbmr/zjaf164","url":null,"abstract":"<p><p>Treatment decisions are being made for a 74-yr-old woman with multiple and recent vertebral fractures. Romosozumab therapy is considered because of its superior efficacy compared to other osteoporosis therapies. However, because of her age, well-controlled hypertension, and mild hyperlipidemia, she is, according to a risk calculator, at high risk for cardiovascular (CV) disease. Romosozumab is contraindicated for patients at very high risk of CV disease, and clinicians are advised to consider the skeletal benefits vs the potential CV risks in patients with CV risk factors. The background information leading to that contraindication and recent real-world evidence about the relationship between romosozumab and CV risk is reviewed to aid in the discussion with the patient and her primary care provider.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"382-386"},"PeriodicalIF":5.9,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145443658","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":"Impaired organic and mineral extracellular matrix composition in early-onset osteoporosis.","authors":"Agnes Ostertag, Bastien Léger, Eugenie Koumakis, Patrice Fardellone, Mylene Zarka, Thomas Funck-Brentano, Guillaume Mabilleau, Martine Cohen-Solal","doi":"10.1093/jbmr/zjaf159","DOIUrl":"10.1093/jbmr/zjaf159","url":null,"abstract":"<p><p>Early-onset osteoporosis (EOOP) is a rare form of primary osteoporosis defined by major skeletal fractures or low BMD that occurs in early age. However, the characteristics of the extracellular matrix that may contribute to bone fragility are unknown. We explored the microarchitecture and bone matrix composition in transiliac bone biopsies (BBs) obtained from adults with EOOP. We compared EOOP BBs to historical control BBs. Microarchitecture was measured by μCT and bone matrix composition by Raman microspectroscopy and Fourier transform infrared spectroscopy. Mechanical response of the bone matrix was investigated by nanoindentation. The contribution of each parameter was assessed by principal component analysis. We compared 18 BBs for EOOP patients (mean [SD] age 34 [8] yr, LS BMD Z-score -2.05 [1.04]) to 19 BBs for age-matched healthy individuals. Patients had vertebral fractures only (n = 7), peripheral fracture only (n = 6) and both vertebral and peripheral fractures (n = 3). Early-onset osteoporosis and controls had similar bone volume (bone volume/total volume, p = .741). As compared with controls, EOOP BBs showed lower trabecular separation (p = .026) and higher trabecular connectivity density (p < .001); cortical thickness was lower in EOOP BBs (p < .01). Also, GAG/Amide III and hydroxyproline/proline ratios as well as accumulation of AGEs were greater in EOOP than controls (all p < .0001). Moreover, tissue mineralization was lower in EOOP than controls, as shown by v1PO4/CH2 ratio, mineral maturity crystallinity and crystal size index (all p < .005). Hardness, indentation modulus and maximum load were all altered in EOOP. Principal component analysis revealed greater contribution of both the organic and mineral matrix phase at the trabecular and cortical EOOP bone rather than bone microarchitecture. The matrix composition of bone showed greater damage of the organic matrix phase and reduced mineralization in EOOP patients than controls, which may explain the high risk of fracture in EOOP patients and may differentiate EOOP from other bone diseases.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"447-456"},"PeriodicalIF":5.9,"publicationDate":"2026-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13034671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145407653","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}