Bone最新文献

{"title":"Involvement of impaired phosphate production and aberrant extracellular ATP signaling in the pathogenesis of hypophosphatasia: Analysis of ALPL-Knockout human iPS cell models","authors":"Miwa Yamazaki ,&nbsp;Ayu Ueta ,&nbsp;Tatsuro Nakanishi ,&nbsp;Kanako Tachikawa ,&nbsp;Masanobu Kawai ,&nbsp;Keiichi Ozono ,&nbsp;Toshimi Michigami","doi":"10.1016/j.bone.2025.117629","DOIUrl":"10.1016/j.bone.2025.117629","url":null,"abstract":"<div><div>Hypophosphatasia (HPP) is caused by inactivating variants of <em>ALPL</em>, the gene encoding tissue non-specific alkaline phosphatase (TNSALP). In order to deepen our understanding of the pathogenic mechanisms of HPP, we herein generated <em>ALPL</em>-knockout (KO) human induced pluripotent stem (iPS) cells by applying CRISPR/Cas9-mediated gene deletion to an iPS clone derived from a healthy subject. We analyzed two <em>ALPL</em>-KO clones, one <em>ALPL</em>-hetero KO clone, and a control clone isogenic except for <em>ALPL</em>. In an osteogenic culture using β-glycerophosphate, which generates inorganic phosphate (Pi) by TNSALP-mediated degradation, <em>ALPL</em>-KO clones showed impaired mineralization, elevated levels of extracellular pyrophosphate (PPi), and reduced levels of extracellular Pi. Osteogenic induction using 3 mM Pi instead of β-glycerophosphate rescued the decreased content of hydroxyapatite in <em>ALPL</em>-KO cells despite the still high levels of extracellular PPi; however, abnormal distribution of hydroxyapatite was noted. Osteoblast lineage cells differentiated from <em>ALPL</em>-KO iPS clones showed the up-regulation of <em>SPP1</em> and the down-regulation of <em>ANKH</em> and the genes for type III sodium/phosphate co-transporters in the culture using β-glycerophosphate, but not when 3 mM Pi was used. Extracellular ATP levels were elevated in osteoblast lineage cells derived from <em>ALPL</em>-KO iPS clones in both culture conditions, which was associated with the down-regulation of <em>P2X7</em> encoding a purinergic receptor. Moreover, osteoblast lineage cells differentiated from <em>ALPL</em>-KO iPS clones in the culture using β-glycerophosphate showed a change in cellular response to extracellular Pi. These results suggest that the reduced local production of extracellular Pi and aberrant ATP signaling play substantial roles in the pathogenesis of HPP.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117629"},"PeriodicalIF":3.6,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011024","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":"Understanding the genetic basis of medication-related osteonecrosis of the jaw: A systematic review","authors":"Sonya Radi ,&nbsp;Deborah Sarah Jans ,&nbsp;Catalina Moreno-Rabié ,&nbsp;Benoit Beuselinck ,&nbsp;Isabelle Cleynen ,&nbsp;Reinhilde Jacobs","doi":"10.1016/j.bone.2025.117623","DOIUrl":"10.1016/j.bone.2025.117623","url":null,"abstract":"<div><div>Medication-related osteonecrosis of the jaw (MRONJ) is an adverse event often associated with the use of antiresorptive drugs. This systematic review aims to identify genes and their polymorphisms associated with the risk of developing MRONJ in patients with oncological or skeletal-related diseases treated with antiresorptive drugs. A systematic literature review was conducted in accordance with PRISMA guidelines. Three electronic databases (PubMed, Scopus, and Web of Science) were searched for studies published up to December 2024. The search strategy included terms such as “MRONJ”, “bone density conservation agents”, and “genetics”. Eligible studies were case control in design, investigating genetic polymorphisms in MRONJ patients compared to controls, which included either healthy individuals or patients receiving antiresorptive drugs without developing MRONJ. Study quality was assessed using the Q-genie tool for genetic association studies. Out of 833 retrieved articles, 27 met the inclusion criteria for qualitative analysis. Most studies were of ‘fair’ quality, with common limitations including small sample sizes, suboptimal control group selection, and ethnic heterogeneity within study cohorts. A total of 136 genetic variants across 58 genes were identified, many of which are involved in biological processes such as immune response and inflammation, cellular function, bone homeostasis, and angiogenesis. However, due to inconsistent findings and a lack of replication across studies, no definitive conclusions regarding specific genetic risk factors could be drawn. The findings of this review suggest that MRONJ susceptibility is likely influenced by multiple variants affecting interconnected biological pathways, particularly involved in immunity, metabolism, angiogenesis, and bone remodelling.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117623"},"PeriodicalIF":3.6,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024909","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 microstructure of metastatic bone lesions suggests tumor mediated alterations in bone mineralization","authors":"Hanwen Fan ,&nbsp;Zhan Xu ,&nbsp;Carla Berrospe Rodriguez ,&nbsp;Noah Dover ,&nbsp;Andrei Demkov ,&nbsp;Morgan Lilly ,&nbsp;Guillermo Aguilar ,&nbsp;Larry J. Suva ,&nbsp;Xiang H.-F. Zhang ,&nbsp;Yuxiao Zhou","doi":"10.1016/j.bone.2025.117625","DOIUrl":"10.1016/j.bone.2025.117625","url":null,"abstract":"<div><div>Breast, prostate and lung cancer cells frequently metastasize to bone, leading to disruption of the bone microstructure. This study utilized mechanical testing coupled with micro-CT imaging, digital volume correlation (DVC), and atomic force microscopy (AFM) nanomechanical testing to examine the mechanical property variations in mouse long bones (tibia) with metastatic lung cancer cell involvement, spanning from the whole-bone scale to the microstructural level. In addition, we also investigated how metastatic invasion alters the morphology of hydroxyapatite nanocrystals in bone at the nanometer scale. The biochemical composition within metastatic lesions was assessed using Raman spectroscopy and correlated with AFM mechanical testing data. Our results demonstrate that lung cancer bone metastasis induces region-specific demineralization and microarchitectural alterations, which likely depend on the local bone matrix structure before tumor invasion. In particular, lamellar cortical bone in the lung cancer cell metastatic region exhibits demineralization both within and between mineralized collagen fibrils, as well as increased porosity. In the tibial crest region, which naturally lacks organized lamellar architecture, demineralization occurs in a spatially nonuniform manner, resulting in the formation of clustered regions with varying mechanical stiffness. These localized differences in mineral and organic content, along with microstructural organization, may contribute to spatial heterogeneity in the mechanical integrity of the tumor-bearing bone, leading to impaired mechanical strength. These findings offer new insights into microstructural alterations within the tumor–bone microenvironment during metastatic progression.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117625"},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008653","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 adiponectin agonist AdipoRon accelerates osteoporosis development in two different models and modulates adipocyte differentiation","authors":"Julia Halper ,&nbsp;Sarah Nicolas ,&nbsp;Federica Gilardi ,&nbsp;Carine Winkler ,&nbsp;Maria Materozzi ,&nbsp;Mariano Schiffrin ,&nbsp;Jean-Yves Jouzeau ,&nbsp;Claudine Blin-Wakkach ,&nbsp;Beatrice Desvergne ,&nbsp;Joelle Chabry ,&nbsp;Didier F. Pisani ,&nbsp;David Moulin","doi":"10.1016/j.bone.2025.117628","DOIUrl":"10.1016/j.bone.2025.117628","url":null,"abstract":"<div><div>Osteoporosis is an increasing concern in the aging population worldwide, culminating in increased economic concerns and diminished quality of life. Similarly, disturbances of lipid metabolism and adipocytes accumulate more and more in western societies and need solutions. Adipocytes have recently attracted much interest in relation to their endocrine products, one of which is adiponectin, normally associated with beneficial effects on cardiovascular health, inflammation, and cancer. In this study, we have investigated the effect of AdipoRon, an adiponectin receptor agonist with reported anti-osteoclastic properties, on the development of osteoporosis in two different preclinical models. Contrasting to our initial hypothesis, AdipoRon treatment accelerated metabolic changes and bone loss in both models. However, AdipoRon rescued bone marrow adipocytes presence induced by glucocorticoids. Investigations on adipocyte differentiation revealed that AdipoRon potently changes adipocyte identity, by exerting opposite effects on adipocyte-gene induction depending on the time point and duration of stimulation. In conclusion, adipocyte-derived Adiponectin deserves further investigation as an autocrine mediator in musculoskeletal research.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117628"},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006925","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":"Plasma proteomic markers of pain and emotional dysfunction in fibrous dysplasia/McCune-Albright syndrome","authors":"Camryn Berry ,&nbsp;Evan E. Hsu ,&nbsp;Courtney LeSon ,&nbsp;Kailey E. Brodeur ,&nbsp;Edin Randall ,&nbsp;Julie Shulman ,&nbsp;Catherine Stewart ,&nbsp;Shealyn O'Donnell ,&nbsp;Boyu Ren ,&nbsp;Ingrid A. Holm ,&nbsp;Alison M. Boyce ,&nbsp;Zachary S. Peacock ,&nbsp;Navil Sethna ,&nbsp;Michael Mannstadt ,&nbsp;Pui Y. Lee ,&nbsp;Jaymin Upadhyay","doi":"10.1016/j.bone.2025.117626","DOIUrl":"10.1016/j.bone.2025.117626","url":null,"abstract":"<div><div>Pain in Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) remains poorly understood and inadequately managed due to uncertainties regarding clinical or biological drivers. This cross-sectional pilot study aimed to use plasma proteomics to identify markers that inform on molecular pathways associated with pain and emotional symptoms in FD/MAS.</div><div>Seventeen individuals (15 females, 2 males), aged 16 to 63 years, with confirmed diagnoses of monostotic FD, polyostotic FD, or MAS participated in a single study visit conducted at Boston Children's Hospital and Massachusetts General Brigham. During the visit, participants completed validated questionnaires assessing neuropathic pain characteristics, pain interference, anxiety symptoms, depression symptoms, and perceived stress, and provided plasma samples. These samples were analyzed for 57 proteins using Olink proximity extension assay. Associations between protein concentrations and symptom scores were evaluated using Spearman's correlations with false discovery rate correction (|r| &gt; 0.5, <em>p</em> &lt; 0.05).</div><div>After FDR correction, the concentrations of seven proteins (TNF-α, LTA, CCL19, CSF2, CCL2, CCL4, CCL7) significantly correlated with pain interference, HADS-depression scores, or perceived stress. Four protein concentrations (TNF-α, CCL19, CSF2, CCL7) significantly correlated with multiple clinical measures.</div><div>This pilot study identified several pain-associated proteins in individuals with FD/MAS, suggesting that proteomic profiling may be a promising approach for discovering pain biomarkers. Larger, longitudinal studies are needed to validate these results and investigate whether targeting immune pathways can alleviate pain and improve emotional health in FD/MAS.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117626"},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006936","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 baseline PINP on the BMD increase with romosozumab, teriparatide, and denosumab in treatment-naïve primary osteoporosis: A retrospective cohort study","authors":"Yuki Etani ,&nbsp;Takaaki Noguchi ,&nbsp;Toshitaka Yukishima ,&nbsp;Tomonori Kobayakawa ,&nbsp;Masafumi Kashii ,&nbsp;Gensuke Okamura ,&nbsp;Atsushi Goshima ,&nbsp;Makoto Hirao ,&nbsp;Taihei Miura ,&nbsp;Takuya Kurihara ,&nbsp;Yuji Fukuda ,&nbsp;Atsushi Sugimoto ,&nbsp;Seiji Okada ,&nbsp;Ken Nakata ,&nbsp;Kosuke Ebina","doi":"10.1016/j.bone.2025.117627","DOIUrl":"10.1016/j.bone.2025.117627","url":null,"abstract":"<div><h3>Purpose</h3><div>To investigate the impact of baseline total N-terminal propeptide of procollagen (PINP) levels on increases in bone mineral density (BMD) after treatment with romosozumab (ROMO), teriparatide (TPTD), and denosumab (DMAb) in patients with treatment naïve primary osteoporosis.</div></div><div><h3>Methods</h3><div>This multicenter, retrospective cohort study included 462 treatment-naïve patients (88.7 % female; mean age, 75.5 years; baseline BMD T-scores: lumbar spine [LS], −3.0; total hip [TH], −2.7) who initiated treatment with ROMO (<em>n</em> = 310), TPTD (<em>n</em> = 70), or DMAb (<em>n</em> = 82). Patients were stratified by baseline total PINP levels into low (≤ 70.1 μg/L) and high (&gt; 70.1 μg/L) groups. After adjusting for baseline characteristics using inverse probability of treatment weighting, changes in BMD were evaluated at 12 months.</div></div><div><h3>Results</h3><div>In the low PINP group, increases in LS BMD were similar between ROMO and TPTD; in the high PINP group, ROMO led to greater increases in LS BMD than TPTD. ROMO resulted in greater increases in TH BMD than TPTD, regardless of PINP level. Compared with DMAb, ROMO resulted in greater increases in LS BMD and TH BMD in the low PINP group, whereas no significant differences were observed in the high PINP group.</div></div><div><h3>Conclusion</h3><div>ROMO demonstrated robust increases in both LS and TH BMD across all PINP levels. TPTD led to increases in LS BMD comparable to those with ROMO in the low PINP group. DMAb led to increases in both LS and TH BMD comparable to those with ROMO in the high PINP group.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117627"},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006950","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 role of probiotics in modulating RANKL in osteoporosis: A systematic review of animal interventional studies and RCTs","authors":"Fatemeh Hamedi-Kalajahi ,&nbsp;Mohammad Alizadeh ,&nbsp;Sorayya Kheirouri","doi":"10.1016/j.bone.2025.117622","DOIUrl":"10.1016/j.bone.2025.117622","url":null,"abstract":"<div><h3>Background</h3><div>Osteoporosis is a major global health concern characterized by reduced bone mass and structural deterioration. The RANK/RANKL/OPG signaling pathway plays a pivotal role in bone remodeling, particularly in osteoclastogenesis. Emerging evidence suggests that probiotics may modulate this pathway through the gut–bone axis, offering potential therapeutic benefits for bone loss.</div></div><div><h3>Objective</h3><div>This systematic review aims to evaluate the effects of probiotic supplementation on Receptor activator of nuclear factor kappa-Β ligand (RANKL) in animal and human interventional studies related to osteoporotic conditions.</div></div><div><h3>Methods</h3><div>A comprehensive literature search was conducted in PubMed, Scopus, and Google Scholar databases up to June 2025. Original interventional studies published in English, including both animal and human models, were selected according to predefined inclusion and exclusion criteria. The selection process followed PRISMA guidelines. Studies were assessed for quality by independent reviewers, and relevant data were extracted for synthesis.</div></div><div><h3>Results</h3><div>A total of 24 studies met the inclusion criteria, most using ovariectomized rodent models and two randomized controlled trials in postmenopausal women. Several probiotic strains—particularly <em>Lactobacillus plantarum</em>, <em>Lactobacillus reuteri</em>, <em>Lactobacillus casei</em>, and <em>Bifidobacterium longum</em>—significantly reduced RANKL expression in animal models, whereas human trials yielded limited or no effect on RANKL despite improvements in other bone turnover markers.</div></div><div><h3>Conclusion</h3><div>Probiotic interventions appear to exert beneficial effects on bone metabolism by modulating RANKL, particularly in estrogen-deficiency-induced osteoporosis models. However, findings from human trials remain limited and inconsistent. Further high-quality RCTs are warranted to confirm these effects and determine optimal strains, dosages, and treatment durations.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117622"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144994732","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":"Response to the letter to the editor: “Comparative effectiveness of romosozumab versus teriparatide for fracture prevention: A new-user, active comparator design”","authors":"Ryoji Tominaga ,&nbsp;Tatsuyoshi Ikenoue ,&nbsp;Ryosuke Ishii ,&nbsp;Noriaki Kurita ,&nbsp;Masataka Taguri","doi":"10.1016/j.bone.2025.117624","DOIUrl":"10.1016/j.bone.2025.117624","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"200 ","pages":"Article 117624"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144931812","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":"Short-term moderate-intensity treadmill running may confer a greater benefit to bone strength than high-intensity treadmill running in 12-month-old C57BL/6 mice","authors":"A.S. Chan ,&nbsp;N. Zare ,&nbsp;M.A. Blank ,&nbsp;J.R. Broatch ,&nbsp;D.J. Bishop ,&nbsp;N.A. Sims ,&nbsp;G.S. Lynch ,&nbsp;I. Levinger","doi":"10.1016/j.bone.2025.117615","DOIUrl":"10.1016/j.bone.2025.117615","url":null,"abstract":"<div><div>Ageing is linked to pathological changes in bone structure and the loss of bone mass and strength. Exercise is a non-pharmacological intervention that may improve bone mass; however, the effects on bone strength, structure, and material properties remain unclear. We tested the effects of work-matched moderate- and high-intensity treadmill exercise on bone structure and strength in the mature (middle-aged) murine skeleton. Twelve-month-old male mice (considered middle-aged in C57BL/6 strain) underwent high-intensity interval training (HIIT, 4 × 4 min, 85–90 % maximum speed) or moderate-intensity continuous training (MICT, 24 min, 60 % maximum speed) three times per week for six weeks. Trabecular and cortical tibial bone microarchitecture were assessed using micro-computed tomography and compared to an age-matched, sedentary cohort and a 12-week-old adult cohort. The effects of ageing were evident in both trabecular and cortical bone, characterised by lower trabecular bone mass, lower cortical area, and thinner yet denser cortices in 12-month-old mice compared to the younger group. Three-point bending tests of the bone, corrected for bone size, revealed that the HIIT tibiae exhibited lower ultimate stress, yield stress, and elastic modulus than the MICT group. While neither HIIT nor MICT significantly differed from sedentary controls, this suggests that moderate-intensity treadmill running in 12-month-old mice may provide greater mechanical protection to the skeleton than high-intensity treadmill running. No significant differences were detected in trabecular or cortical bone mass or structure between exercised and sedentary groups, apart from trabecular separation, which was lower in the HIIT group, suggesting a mild benefit. Future studies should explore whether extended training and/or incorporating resistance exercise into these interventions could increase bone strength in older mice.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"201 ","pages":"Article 117615"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144989558","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":"Empirical quantification of bone mineral and organic phase attenuation coefficients using CT imaging and controlled thermal processing","authors":"Yunhua Luo ,&nbsp;Ashish Bhattarai ,&nbsp;Michael Jackson","doi":"10.1016/j.bone.2025.117621","DOIUrl":"10.1016/j.bone.2025.117621","url":null,"abstract":"<div><div>Accurate quantification of bone mineral, organic, and water phases is critical for evaluating bone quality, assessing fracture risk, and diagnosing skeletal diseases. Dual-energy computed tomography (DECT) holds promise for decomposing these phases but fundamentally relies on precise linear attenuation coefficients (LACs) for each phase. Existing surrogate-based imaging methods—typically assuming fixed phase attenuation coefficients—fail to reflect the compositional heterogeneity of native bone, leading to systematic errors in decomposition. This study presents a novel empirical framework for determining the average LACs of bone mineral and organic phases using 28 standardized cylindrical bovine bone specimens. The method integrates high-resolution CT imaging with a controlled drying–ashing protocol to isolate phase-specific masses and volumes. In conjunction with a linear mixture attenuation model, specimen-wise average LACs for the bone, mineral, and organic phases were characterized at selected energy levels. Results showed the following: 1) Average LACs had wide variability across the specimens, <em>e.g.</em>, ranging from 1.16 to 2.38 cm⁻¹ for mineral phase and 0.004–0.085 cm⁻¹ for organic phase at 45 kV, highlighting the limitations of using fixed surrogate-based values. 2) Bone density correlated more strongly with organic density than with mineral density, emphasizing the importance of accurately quantifying the organic phase for bone quality and health assessment. 3) Bone LACs were strongly correlated with mineral LACs but not with organic LACs, underscoring the inability of single-energy CT to capture meaningful information from the organic phase. The proposed empirical framework demonstrates the feasibility of characterizing phase-specific LACs in real bone tissue and may support physiologically accurate DECT modeling, advancing personalized, composition-based bone diagnostics.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"200 ","pages":"Article 117621"},"PeriodicalIF":3.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925194","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}