Journal of Bone and Mineral Research最新文献

{"title":"Pro-inflammatory immune microenvironment and Thrombospondin-1-positive monocytes as drivers of osteoclastogenesis in postmenopausal osteoporosis.","authors":"Ming Li, Huanxin Sun, Liu Liu, Yunna Ning, Yongzhi Cao, Bingru Lu, Yueran Zhao, Mingjie Kuang, Dachuan Wang","doi":"10.1093/jbmr/zjaf083","DOIUrl":"10.1093/jbmr/zjaf083","url":null,"abstract":"<p><p>Postmenopausal osteoporosis (PMOP) is driven by an imbalance in the interaction among osteoclasts, osteoblasts, and immune cells within the bone marrow microenvironment. However, detailed single-cell transcriptomic data on the bone microenvironment of PMOP patients are lacking. This study characterized the cellular landscape of the bone marrow in PMOP and identified key osteoclastogenic pathways. Single-cell RNA sequencing of bone marrow cells from 10 PMOP patients and 10 controls (totaling 93 867 cells) was performed, complemented by histological validation and in vitro modulation of key pathways. The findings revealed elevated expression of cytokines and chemokines in specific cell subpopulations, including hematopoietic stem cells, B cells, T cells, dendritic cells, neutrophils, granulocyte-macrophage progenitors, and erythroid cells, which are likely to contribute to the promotion of osteoclastogenesis. Enhanced differentiation of monocytes into osteoclasts was linked to elevated B cell communication. Furthermore, 3 monocyte subsets (THBS1+ with CCL20+, or LRP1+, or C1QA+) exhibited osteoclastogenic potential, associated with the activation of the Nucleotide-binding Oligomerization Domain (NOD)-like receptor pathway. Targeting THBS1 significantly reduced bone loss in PMOP mouse models. This study provides a detailed characterization of bone marrow cell heterogeneity in postmenopausal women, offering insights into potential therapeutic strategies targeting PMOP.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1061-1076"},"PeriodicalIF":5.9,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293030","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":"Cross-sectional and longitudinal associations between statin use and bone density: the Manitoba BMD registry.","authors":"William D Leslie, Fatima Zarzour, Neil Binkley, Suzanne N Morin, John T Schousboe","doi":"10.1093/jbmr/zjaf077","DOIUrl":"10.1093/jbmr/zjaf077","url":null,"abstract":"<p><p>Statins are among the most widely prescribed medications in older individuals. Inconsistent data in humans suggest that statin medications may be associated with greater BMD and lower risk for osteoporosis. We identified 22 393 individuals aged 40 yr and older undergoing initial (Visit 1) and repeat (Visit 2) TH BMD measurement within 1-10 yr total from DXA through the Manitoba BMD Program (February 28, 1999 to March 29, 2018). Linked medication records showed that 4119 (18.3%) of the study population were statin users at Visit 1 and 6667 (29.8%) were statin users at Visit 2. There was inconsistent and largely negative evidence for prior statin use affecting initial TH BMD measurement or BMD change during follow-up. Even among those with the greatest exposure (mean 5.1 yr of prior statin use with high adherence), the observed effects on covariate-adjusted initial TH BMD or annualized change in TH BMD change did not show clinically significant differences. In summary, this large observational analysis, which included both cross-sectional and longitudinal components, failed to detect a clinically meaningful benefit of statin exposure on bone density, even when taken with high adherence over several years.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1045-1051"},"PeriodicalIF":5.9,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406123/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172107","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":"Effects of vitamin D3, omega-3s, and a simple home exercise program on incident vertebral fractures: the DO-HEALTH randomized controlled trial.","authors":"Melanie Kistler-Fischbacher, Gabriele Armbrecht, José A P Da Silva, Caroline de Godoi Rezende Costa Molino, Robert Theiler, René Rizzoli, Bruno Vellas, Bess Dawson-Hughes, John A Kanis, Lorenz C Hofbauer, Endel John Orav, Reto W Kressig, Andreas Egli, Guido A Wanner, Heike A Bischoff-Ferrari","doi":"10.1093/jbmr/zjaf058","DOIUrl":"10.1093/jbmr/zjaf058","url":null,"abstract":"<p><p>Vertebral fractures (VFs) are among the most common osteoporotic fractures. The effect of vitamin D3, omega-3s or a simple home exercise program (SHEP) on VFs is unclear. We examined whether vitamin D3, omega-3s, or SHEP, alone or in combination, over 3 years, reduce the incidence rate of VFs among European older adults. DO-HEALTH is a multi-center, 2 × 2 × 2 factorial design, randomized controlled trial, which included older adults (≥70 years) free from major health events in the 5 years prior to enrollment. The study interventions were vitamin D3 (2000IU/d), omega-3s (1 g/d), and SHEP (3 × 30 min/wk), applied alone or in combination. Quantitative and qualitative VF assessment was determined from lateral thoracolumbar DXA scans. The primary outcome for this analysis was the incidence rate (IR) of total VFs, defined as the number of any new and progressed VFs over the 3-year follow-up. Sensitivity analyses were conducted for only new VFs and only VF progressions. Negative binomial regression models were fit, adjusted for age, sex, prior fall, BMI, study site and participants' follow-up time. 1488 participants (mean age 74.9 years; 77% had low bone mass or osteoporosis; 43.8% had 25(OH)D levels <20 ng/mL) were included. There were 93 incident VFs, of which 58 were new VFs and 35 were progressions. None of the three treatments reduced the IR of total VFs overall, however, the IR was reduced with SHEP compared to the control exercise program in women (IR ratio 0.52, 95% CI 0.28, 0.98). In the sensitivity analysis for VF progressions, SHEP reduced the IR (IR ratio 0.34, 95% CI 0.16, 0.75). Among generally healthy older adults, vitamin D3 and omega-3s supplementation did not reduce the incidence rate of VFs. SHEP reduced the incidence rate of total VFs in women and of VF progressions overall. Exercise may play a role in the prevention of VFs.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"1035-1044"},"PeriodicalIF":5.9,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12406121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144256918","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":"Advances in PTH-based Medicines.","authors":"Anne-Laure Bonnet, Lizaveta Aboishava, Michael Mannstadt","doi":"10.1093/jbmr/zjaf118","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf118","url":null,"abstract":"<p><p>Parathyroid hormone (PTH), produced by the parathyroid glands, plays a critical role in the regulation of calcium and phosphate homeostasis, acting primarily on bone and kidney to maintain serum calcium levels within a narrow range. PTH also plays important roles in bone remodeling by directly stimulating osteoblasts and osteocytes, integrating its calcemic response with stimulation of bone formation. Through the RANK/RANK-ligand system, these cells activate osteoclasts, promoting a balanced process of bone formation and resorption that maintains bone density and strength. Dysregulation of PTH, as seen in disorders such as hyper- and hypoparathyroidism, can lead to significant clinical complications. In recent years, major advancements have been made in the development of PTH analogs, aimed at leveraging PTH's physiological effects on bone to treat conditions such as osteoporosis and hypoparathyroidism. While PTH promotes both bone formation and bone resorption, the net outcome may be a gain or loss of bone mass, depending largely on the administration pattern of PTH or its analogs. When PTH is given intermittently (for example, as once-daily subcutaneous injection), bone formation is favored. Continuous administration of PTH or chronic elevation of blood PTH levels as seen in primary hyperparathyroidism tend to promote bone resorption. PTH analogs, such as teriparatide (PTH(1-34)) and the PTHrP analog abaloparatide, administered once daily, have significant efficacy in stimulating bone formation, making them valuable options for the treatment of osteoporosis. Given this capacity to improve bone structure, these analogs hold broader therapeutic potential for other skeletal disorders, including fracture healing and oral bone repair, which expands the scope of PTH-based therapies beyond osteoporosis. Long-acting PTH analogs have applications in treating hypoparathyroidism, offering an alternative to conventional treatment with calcium and active vitamin D. This article reviews the molecular mechanisms of approved and emerging PTH-based medicines, their clinical applications, and recent advances in optimizing their therapeutic potential. We also discuss ongoing research aimed at developing next-generation PTH analogs with improved efficacy for skeletal and metabolic disorders.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937309","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":"Non-physiological direction loading increases bone adaptive responses by enhancing lacunocanalicular fluid dynamics.","authors":"Yuan Wang, Ruisen Fu, Haisheng Yang","doi":"10.1093/jbmr/zjaf117","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf117","url":null,"abstract":"<p><p>It's been proposed that bone adaptation is \"error-driven\", namely, bone is more sensitive to non-physiological loading (e.g., loading in a non-physiological direction). However, the effect of physiological vs. non-physiological loading on bone adaptation and its underlying mechanism are not fully understood. We hypothesized that loading in a non-physiological direction would increase osteogenesis via enhancing fluid flow within the lacunocanalicular network (LCN), independent of the strain magnitude. To test this hypothesis, we first examined the effects of physiological and non-physiological direction loading on bone formation responses with axial and transversal in vivo loading models of the mouse tibia, respectively, under a strain-matched condition. Next, an in silico whole bone-LCN multiscale model was developed to compute loading-induced strains and fluid shear stresses within the LCN. Lastly, regression analyses were performed to examine the spatial correlations between bone mechanoresponses and fluid shear stress (and strain). Results showed that the transversal loading led to an increased cortical bone response compared to the axial loading even though the strains were matched. The transversal loading-induced increase in bone response was associated with enhanced lacunocanalicular fluid flow rather than strain. Additionally, strong correlations existed between bone mechanoresponses and fluid shear stress whereas no correlation was detected between bone responses and strain. These results support our hypothesis and may explain why bone adaptation is more sensitive to loading in a non-physiological direction. The findings also highlight the key role of the fluid dynamic microenvironment within LCN in regulating bone mechanoadaptation.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937413","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":"Atypical fractures at non-classical sites associated with anti-resorptive therapy: a systematic review.","authors":"Maria P Yavropoulou, Socrates E Papapoulos","doi":"10.1093/jbmr/zjaf115","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf115","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144937352","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":"Fracture Risk Scores Using Output from an Opportunistic Screen of Low Bone Density from Conventional X-ray.","authors":"Catriona A Syme, Mark D Cicero, Jonathan D Adachi, Claudie Berger, Suzanne N Morin, David Goltzman, Alexander Bilbily","doi":"10.1093/jbmr/zjaf113","DOIUrl":"10.1093/jbmr/zjaf113","url":null,"abstract":"<p><p>Fracture risk is commonly assessed by FRAX, a tool that estimates 10-year risk for major osteoporotic fracture (MOF) and hip fracture. FRAX scores are often refined by additionally including femoral neck (FN) bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) as an input. Rho™, a novel AI-powered software, estimates FN BMD T-Scores from conventional x-rays, even when FN is not in the image. Whether a FRAX score using this estimate (FRAX-Rho) can improve a FRAX score without a T-Score input (FRAX-NoT) has not been studied. We conducted a retrospective analysis of Canadian Multicentre Osteoporosis Study participants who had x-rays of the lumbar and/or thoracic spine, FRAX risk factors, and DXA T-Scores acquired at the same time point, and follow-up fracture outcomes over 9 years. In 1361 participants with lumbar x-rays, FRAX-Rho and FRAX with DXA FN T-Scores (FRAX-DXA) had very good agreement in categorizing participants by MOF risk (Cohen's weighted kappa κ=0.80 [0.77-0.82]), which tended to be better than that between FRAX-NoT and FRAX-DXA (0.76 [0.73-0.79]). Agreement in categorizing participants by hip fracture risk was significantly greater between FRAX-Rho and FRAX-DXA (0.67 [0.63-0.71]) than FRAX-NoT and FRAX-DXA (0.52 [0.48-0.56]). In predicting true incident MOF, FRAX-Rho and FRAX-DXA did not differ in their discriminative power (c-index) (0.76 and 0.77; p=0.36) and both were significantly greater than that of FRAX-NoT (0.73; p<0.004). The accuracy of FRAX-Rho for predicting MOF (Brier Score) was better than FRAX-NoT (p<0.05) but not as good as FRAX-DXA. Similar results were observed in participants with thoracic x-rays. In conclusion, FN T-Scores estimated by Rho from lumbar and thoracic x-rays add value to FRAX-NoT estimates and may be useful for risk assessment when DXA is not available.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870606","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":"Increase in Serum DKK1 Levels Attenuates the Anabolic Response to Romosozumab in Postmenopausal Osteoporosis.","authors":"Giovanni Adami, Filippo Montanari, Angelo Fassio, Francesco Pollastri, Anna Piccinelli, Camilla Benini, Emma Pasetto, Mattia Tugnolli, Davide Gatti, Maurizio Rossini, Ombretta Viapiana","doi":"10.1093/jbmr/zjaf110","DOIUrl":"10.1093/jbmr/zjaf110","url":null,"abstract":"<p><strong>Background: </strong>Romosozumab is a monoclonal antibody against sclerostin that initially exhibits potent anabolic effects in treating osteoporosis. However, its efficacy diminishes after 6 mo, with bone formation markers declining despite continued therapy. We hypothesized that increased levels of Dickkopf-1 (Dkk1), a Wnt pathway inhibitor, may contribute to this attenuation by suppressing osteoblast activity.</p><p><strong>Methods: </strong>We conducted a 12-monht prospective observational study on post-menopausal osteoporosis naïve to anti-osteoporosis treatment treated with romosozumab. Serum levels of Dkk1, Procollagen Type I N-Terminal Propeptide (P1NP), C-terminal telopeptide of type I collagen (CTX), and sclerostin were measured at baseline (M0) and at 3 (M3), 6 (M6), and 12 mo (M12). Bone mineral density (BMD) at the lumbar spine, femoral neck, and total hip was assessed at M0, M6, and M12. Associations between Dkk1 and P1NP were analyzed using linear mixed-effects models.</p><p><strong>Results: </strong>Dkk1 levels increased significantly from 38.9 pmol/L at M0 to 44.2 pmol/L at M12 (p = .003). P1NP increased from 89.4 ng/mL at M0 to 115.4 ng/mL at M3 (p = .004) but decreased to 61.5 ng/mL by M12 (p < .001). CTX decreased significantly throughout the study (p < .001). BMD increased significantly at all sites by M12 (lumbar spine + 13.8%, femoral neck + 6.3%, total hip + 4.7%; all p < .01). An inverse association was found between Dkk1 increase and P1NP decrease between M3 and M12 (estimate = -0.909; p = .032).</p><p><strong>Conclusion: </strong>Romosozumab treatment is associated with a significant rise in Dkk1 levels, which correlates with a decrease in bone formation markers over time. Dkk1 may attenuate the anabolic effects of romosozumab by inhibiting Wnt signaling.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870607","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":"Editorial on \"Plasma fatty acid composition predicts bone mineral accrual from childhood to adolescence: the PANIC study.","authors":"Lisa Langsetmo","doi":"10.1093/jbmr/zjaf114","DOIUrl":"10.1093/jbmr/zjaf114","url":null,"abstract":"","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Associations Between Changes in Bone Mechanical Strength and Fracture Risk Estimated by FRAC.","authors":"Annabel R Bugbird, Danielle E Whittier, Lauren A Burt, Steven K Boyd","doi":"10.1093/jbmr/zjaf111","DOIUrl":"https://doi.org/10.1093/jbmr/zjaf111","url":null,"abstract":"<p><strong>Introduction: </strong>Monitoring bone health for osteoporosis is typically based on measuring areal bone mineral density (aBMD). However, widely used fracture risk prediction tools are primarily driven by clinical risk factors and show limited sensitivity to underlying bone changes over time. This study evaluated the ability of the new Microarchitecture Fracture Risk Assessment Calculator (FRAC) to detect longitudinal changes in fracture risk in relation to bone quality.</p><p><strong>Methods: </strong>Our study cohort included 601 participants (70.2% female) from a longitudinal population study. HR-pQCT scans of the distal radius and tibia were acquired at two visits, 3-10 years apart. The FRAC 5-year risk of major osteoporotic fracture (MOF) was calculated at both time points. Participants were divided into quartiles based on the absolute change in tibia bone strength between study visits to assess the model's sensitivity to changes in bone fragility. Differences between quartiles were assessed using a Mann-Whitney U test and the standardized response mean (SRM). Additionally, changes in fracture risk by decade, were analyzed to investigate age- and sex-specific trends in fracture risk.</p><p><strong>Results: </strong>The average age of participants was 53.8 ± 15.4 years, with an average follow-up of 6.8 ± 1.8 years. The greatest absolute annualized changes in FRAC risk occurred in individuals with the largest differences in bone strength (SRM = 0.73-0.78), while the least change was observed in individuals with minimal changes (SRM = 0.07-0.21). Age- and sex-specific trends aligned with previously established patterns of bone aging, showing the greatest annualized changes in fracture risk in menopausal females (40-60 years) and older adults (70+ years).</p><p><strong>Conclusion: </strong>We demonstrated FRAC is sensitive to changes in fracture risk driven by declines in bone quality in aging adults. These results suggest FRAC is well suited for tracking fracture prediction longitudinally and has potential to monitor osteoporosis disease progression and treatment response.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870608","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}